Abstract
With the advent of long-duration lunar and Martian space missions, health risks will increase significantly as astronauts will be exposed to prolonged periods of reduced gravity, elevated radiation levels, celestial dust, and isolated environments that may interfere with psychological health and sleep. Astronauts will increasingly rely on pharmaceutical intervention to mitigate these health risks, particularly drugs targeted to treat spaceflight-induced medical conditions such as bone loss, cytopenias, and other degenerative conditions secondary to radiation exposure and immune system dysfunction. Many of these are biologic drugs, and peptide and protein pharmaceuticals are particularly unstable, with limited shelf life (∼6 months) even with refrigeration, which is inadequate for a 2+-year mission to Mars and back. In addition to reduced drug stability in space, there are mass/volume constraints, uncertainty regarding how much—if any—of the drugs will be needed, and severely limited re-supply opportunities. The National Aeronautics and Space Administration (NASA) has identified the need to establish a drug formulary for long-duration space missions, along with a process to ensure that medications remain efficacious during flight. To address these challenges, we aim to develop an “Astropharmacy,” a compact platform that uses engineered microbes to produce small doses of biologics on demand, either in transit or at space destinations that may be far from Earth. To assess the potential for this Astropharmacy, we have compiled a database of peptide and protein drugs that may be needed to mitigate the health risks during long-duration missions to the Moon and Mars that are well-suited for production by the Astropharmacy system. The compiled database acts as a guide for drugs that could be produced using the Astropharmacy system. Importantly, the database can also serve as a valuable resource for flight surgeons and the medical community on Earth, particularly those providing care in resource-limited environments, along with researchers studying biologic drug development.
1 Introduction
During spaceflight, astronauts are exposed to prolonged reduced gravity, ionizing radiation, and an isolated, high-stress environment, which all pose significant risks to human health. The impacts of spaceflight on human health have been extensively studied and reviewed (; ; ; ). These impacts span across many body systems, including the musculoskeletal (; ), cardiovascular (; Shen and Frishman, 2019), immune (; ), lymphatic (), vestibular (; ), and nervous systems (; Seidler et al., 2024). In addition to physical hazards, the extreme environment of space can also result in mental and psychosocial challenges. The isolation and disruption of the circadian rhythm can lead to long-term composite stress, contributing to sleeping problems and increasing the rate of anxiety and depression in astronauts (Yin et al., 2023). All these pose risks to astronaut health and thus to mission success.
Nevertheless, astronauts have lived and worked onboard the International Space Station (ISS) in Low Earth Orbit (LEO) for the past 25 years. In addition to countermeasures (e.g., specialized diet and exercise) developed to mitigate the negative impacts of spaceflight, astronauts aboard the ISS have access to commercial over-the-counter and prescription medications for common ailments, such as headaches, sleep issues, congestion, diarrhea, and motion sickness (; Wotring, 2015). Although historical medication usage aboard the ISS is poorly documented, the Dose Tracker study of six crew members reported an average of four medication uses per week per crew member, totaling 453 medication uses per crew member during the 5–6-month missions (). Medications are most commonly used for sleep issues, congestion, allergies, or pain, often associated with extracurricular activities or exercise (Wotring, 2015). These medications are supplied from Earth and can be easily replaced upon reaching their expiration date as part of regular resupply missions (). Overall, despite extensive changes to the human body in space, the health risks in LEO are considered low due to limited mission durations, effective countermeasures, a well-established medical supply, and proximity to Earth in case of emergencies.
We are entering a new era in human space exploration as the National Aeronautics and Space Administration (NASA) and other space agencies plan long-duration missions (>6 months) to the Moon and Mars. The health risks will increase significantly during these missions to deep space as astronauts will be exposed to prolonged periods of reduced gravity, elevated radiation levels, celestial dust, and isolated environments that may interfere with psychological health and sleep. Although mission durations on the ISS average ∼6 months (Tomsia et al., 2024), the proposed missions to Mars will last ∼18–30 months (Figure 1). The prolonged exposure to microgravity can intensify the musculoskeletal impacts observed in LEO. For example, continued bone degeneration increases the risk of fractures, osteoporosis, and renal stone formation, conditions that are difficult to treat in flight (Sibonga et al., 2019) and can lead to medical emergencies if left untreated. The radiation dose equivalent is expected to increase from 50 to 100 mSv during a 6-month ISS mission to 300–400 mSv during 1-year sustained lunar operations, 500–600 mSv in a deep-space habitat for 1 year, and 870–1,200 mSv during a 650–920-day Mars mission (Simonsen et al., 2020). Prolonged radiation exposure affects almost all of the body’s organ systems and can increase the risk of cancer through DNA damage (). For example, radiation exposure can cause damage to the cardiovascular system through promotion of myocardial remodeling, fibrosis, and microvascular damage (). Additionally, short-term exposure to a high dose of radiation, such as during a solar particle event, can result in acute radiation sickness, with potentially life-threatening complications, such as neutropenia (low white blood cell count) (). Celestial dust exposure is another challenge that was first encountered during the Apollo missions. Although Apollo missions lasted only several days, prolonged exposure to celestial dust during deep-space missions will increase the risk of ocular and pulmonary injuries (Scully et al., 2015). NASA’s Human Research Program identified more than 30 human health risks associated with spaceflight (Patel et al., 2020), and most of these risks would require mitigation for lunar and Mars missions, according to NASA’s Human Research Roadmap.
FIGURE 1
Far away from Earth, medical evacuation is not feasible, so astronauts increasingly rely on pharmaceutical intervention to mitigate these health risks (; ). However, supplying these pharmaceuticals would be challenging due to their limited shelf life, reduced drug stability in space, mass/volume constraints, and uncertainty regarding how much—if any—of the drugs would be required, all in the face of severely limited re-supply opportunities. Approximately 60% of ISS medications have a terrestrial shelf life of 36 months or less in their original packaging, and approximately 15% expire in less than 24 months (). However, these medications are often removed from their original packaging before spaceflight and placed into polypropylene containers to meet the mass/volume constraints. This repackaging is not protective against atmospheric factors and may contribute to accelerated drug degradation (Reichard et al., 2023). Drug degradation may be further accelerated by exposure to space radiation, variations in gravity, and vibrations (; ; Reichard et al., 2023; Wotring, 2016). Some drugs that have been identified by NASA as particularly susceptible to instability and bacterial growth during spaceflight include eye drops, nitroglycerin, liquid antibiotics, and insulin (). Drug degradation leads to reduced potency and accumulation of impurities (drug degradation products). Commonly, drugs fail to meet the United States Pharmacopeia requirements for stability if the concentration of active pharmaceutical ingredients is not within 10% of the label specifications (). After 550 days in space, one study found that melatonin failed to meet this stability requirement, while drug degradation products were found in aspirin, ibuprofen, and amoxicillin–clavulanate (Wotring, 2016). However, studies on drug degradation in space have so far been limited by methodological challenges, such as the lack of terrestrial controls and small sample size (Reichard et al., 2023). These studies have also been completed in LEO, where the Earth’s magnetic field provides some protection against radiation compared to deep-space missions. Although these concerns are mitigated on the ISS by replacing expired drugs on resupply missions, this would not be feasible on future long-duration missions, particularly to Mars. NASA’s Human Research Roadmap includes the “Risk of Ineffective or Toxic Medications During Long-Duration Exploration Spaceflight” that requires mitigation for Mars missions and identifies the need to determine optimal packaging, storage, and drug formulations, along with the need for further characterization of medication stability under the spaceflight environment.
Biological drugs, pharmaceuticals derived from living organisms or their components, could be particularly well suited to treat spaceflight-induced medical conditions. In particular, peptide and protein biologics are particularly useful. On Earth, biological drugs accounted for 40% of new drugs approved by the U.S. Food and Drug Administration (FDA) in 2022 (), with 600 peptide drugs in preclinical studies as of 2023 (Rossino et al., 2023). The peptide drug industry is predicted to grow at a compound annual growth rate of 10% over the next 10 years (Rossino et al., 2023). Many peptide drugs on the market today are used to treat metabolic, cardiovascular, or endocrine conditions (Wang et al., 2022). Peptides have also been used for the treatment of radiation-induced complications, such as neutropenia (), and investigated as radioprotective agents (Shaghaghi et al., 2021). In the case of astronaut health, these peptide drugs could be used to treat bone loss, cytopenias, and other degenerative conditions secondary to radiation exposure and immune system dysfunction. Unfortunately, there are serious challenges associated with using peptide and protein biologics for long-duration flights. Primary among these is their very limited shelf life of ∼6 months, which is inadequate for a 2+-year mission to Mars and back (; ; Vallota-Eastman et al., 2023). Refrigeration and freezing temperatures are often required for their storage, which is challenging to provide during deep-space spaceflight due to the significant associated up-mass and volume. Additionally, spaceflight unpredictably accelerates the degradation of peptide-based drugs, indicating that such drugs have been dismissed from medical kits, despite their promising efficacy and safety. Consequently, the spaceflight community has expressed the need for in-space manufacturing of materials, including medicine, to support astronauts’ health and performance in deep space (Seoane-Viano et al., 2022).
To address these challenges, several studies have focused on alternative drug formulations (e.g., the addition of photoprotective agents) and packaging to increase drug stability in space (Wani et al., 2024). We aim to investigate an alternative approach, in which required medications can be produced on-site if and when they are needed, eliminating the need for long-term storage. This approach should be capable of producing a therapeutic dose of the required medication within 24 h–48 h, use stable reagents that can be stored at room temperature, and have minimal mass, volume, power, and crew-time requirements. To achieve this, we aim to develop an “Astropharmacy,” a compact platform that uses engineered microbes to produce small doses of biologics on-demand at space destinations that may be far from Earth (Vallota-Eastman et al., 2023). Engineered microbes can be transported to deep space in the form of durable, dried spores, along with the Astropharmacy hardware. If an astronaut becomes ill, the spores can be activated to initiate production of the desired biologic. This platform would become particularly critical on missions of >6 months with limited re-supply and storage capabilities, such as a mission to Mars. To assess the potential of our Astropharmacy to meet the demand for pharmaceutical countermeasures, we compiled a database of biologics that could be produced by microbes and may be needed to mitigate the health risks during long-duration missions to the Moon and Mars. We focused on peptide and protein drugs as they can commonly be produced by microbes. This is the first formulary of peptide-based medications for deep-space missions and can help define the current landscape and opportunities to use this unique class of drugs in treating spaceflight-induced medical conditions. With this, we demonstrate that Astropharmacy has the potential to become a valuable resource for flight surgeons and for the medical community on Earth, particularly for those providing care in resource-limited environments.
2 Materials and methods
The methodology to compile the database was divided into six stages (Figure 2), as discussed in detail in the following sections.
FIGURE 2
2.1 Stage 1: establishing the database from historical ISS usage
The database began as a list of the pharmaceuticals named in the International Space Station Integrated Medical Group (IMG) Medical Checklist (). This comprehensive, 1000-page medical manual was published by NASA’s Mission Operations Directorate in 2001 and was developed in collaboration with international partners to reflect the standards adhered to by all astronauts on the ISS. This medical checklist defines protocols for astronaut health management to be used by the flight surgeon on Earth, who advises the crew in real-time, the crew medical officer designated to handle medical issues onboard, and all crew members (Yule et al., 2023).
2.2 Stage 2: addition of peptide drugs useful for long-duration missions
We reviewed the literature on peptide-based drugs that have been used on Earth to treat conditions that may also arise on long-duration deep-space missions. This literature was found primarily using PubMed and Google Scholar, with keywords such as “pharmaceutical countermeasures,” “microgravity,” “radioprotection,” and “space medicine.” Further research was then performed to determine which of these drug candidates were peptide-based and, therefore, would be added to the database. Considering the rapidly growing number of peptide-based drugs, we also consulted general lists of recently approved (or nearly approved) peptide-based drugs. These data were found in the published literature (Wang et al., 2022; Rossino et al., 2023). We reviewed the peptide-based drugs from these lists to identify those that are used on Earth to treat medical conditions that are also anticipated during deep-space missions. This included indications related to the treatment of radiation exposure, osteoporosis, neutropenias, pain, sleep difficulties, and other conditions. Once peptide-based drugs of interest were identified, the following information was compiled for each drug: common/brand names, function, drug class, FDA approval status and indication, shelf life and storage conditions, interest to NASA, amino acid length, and a review of prior transgenic production.
2.3 Stage 3: FDA approval status
FDA approval status was documented to indicate the drug development stage and whether the drug has demonstrated safety and efficacy on Earth. Although drug effectiveness may be impacted in space, the U.S. crew onboard the ISS currently use commercial, FDA-approved medications. The “Drugs@FDA: FDA-Approved Drugs” database was used to determine a drug’s current approval status, while FDA drug labels available online were particularly useful for gathering information regarding drug storage and shelf life. For non-FDA-approved drugs, clinical trial history was searched on ClinicalTrails.gov, a database from the National Institute of Health. In some cases, information on shelf life and storage was instead obtained from the manufacturer’s website.
2.4 Stages 4–5: indications for use, storage conditions, and shelf life
Pharmaceutical company websites often contain information regarding drug indications, shelf life, and storage. Further basic information for each drug was collected from PubChem, a free and public database of chemical information maintained by the U.S. National Institute of Health, National Center for Biotechnology Information, and the U.K.’s electronic medicines compendium (eMC), an online database of regulated medicine maintained by Datapharm Ltd., an independent U.K. company, with oversight from the Medicines and Healthcare Products Regulatory Agency and the European Medicines Agency. PubChem offers chemical structures, physical and chemical properties, biological activities, toxicity information, pharmacological data, health and safety information, associations with peer-reviewed publications, and drug mechanisms. eMC is updated monthly by hundreds of pharmaceutical companies to document product characteristics and patient information. In some instances, we consulted other health departments outside the U.S. or the U.K. for additional information. For example, we referenced The Drug and Health Product Register, an online medicinal database maintained by Health Canada, and the Therapeutic Goods Administration from the Australian Government’s Department of Health and Ageing. DrugBank, a medicinal database maintained by the University of Alberta (Wishart et al., 2006), was also used to find amino acid sequence information.
2.5 Stage 6: transgenic production from PubMed and Google Scholar
To determine whether a peptide drug has been produced recombinantly (as opposed to chemical synthesis or isolation from an animal), we search the published literature on PubMed, Google Scholar, and Google Patents. Keywords such as the drug name followed by “recombinant production,” “transgenic production,” “production in Bacillus subtilis,” and “production in Escherichia coli” were used. Once an article or patent was identified, it was reviewed to determine which host expression system was used for peptide production. We particularly focused on microbial or yeast expression systems as they are best suited for spaceflight and, thus, have better utility for the Astropharmacy platform.
2.6 Data analysis and figure preparation
Data analysis and figure preparation were conducted using GraphPad Prism 10.1.2 (Dotmatics). The database was compiled in the web-based spreadsheet application Google Sheets (Google), which allowed for collaboration across the geographically distributed team, version control, and integration with other Google Workspace tools or file formats.
3 Results and discussion
3.1 Insights from current medications onboard the International Space Station
We reviewed 92 medications currently in use on the ISS to identify medications that could be produced recombinantly by microbes and, thus, could be investigated for production in the Astropharmacy platform. This platform would be ideal for the production of peptide-based drugs with a short shelf life or that require refrigeration or freezing for storage. Given the relatively short mission durations and non-medical countermeasures (e.g., diet and exercise), astronauts on the ISS generally do not have to rely on pharmaceutical countermeasures to mitigate the health risks associated with spaceflight. Thus, the current supply of medications largely serves as a “first aid kit” to treat common ailments (e.g., infections, colds, nausea, diarrhea, sleep issues, headaches, muscle soreness, and motion sickness) or medical emergencies (e.g., severe allergic reactions and heart issues). These common ailments can be treated with non-peptide drugs that generally have a longer shelf life and may be stored at room temperature. We found that only 1 out of 92 catalogued drugs, the bacitracin antibiotic, was peptide-based and could, therefore, potentially be produced on-demand in the Astropharmacy. It is naturally produced by Bacillus licheniformis and B. subtilis, although engineered biosynthesis of bacitracin has also been demonstrated in B. subtilis (). Additionally, the antifungal cream clotrimazole and the antiviral agent oseltamivir have peptide-based alternatives that may be good candidates for on-demand production using the Astropharmacy platform.
3.2 A database of peptide-based medications to mitigate the health risks in deep space
During deep-space missions, astronauts increasingly rely on pharmaceutical intervention to mitigate the health risks associated with the hazards of spaceflight. On-demand production of pharmaceuticals can mitigate the challenges such as limited shelf life, storage and up-mass constraints, and the inability to restock. We compiled a database of peptide-based medications used on Earth to treat conditions that may also be induced by spaceflight and could be investigated for production in the Astropharmacy. We identified 30 peptide drugs that are used on Earth but are not currently in use by NASA or other space agencies and organized them into eight categories based on their function (Table 1). The identified peptide drugs were compiled into a database containing information on common/brand names, function, drug class, FDA approval status and indication, shelf life and storage conditions, interest to NASA, amino acid length, and a review of prior transgenic production (Table 2).
TABLE 1
| Drug category | Peptide drugs | % of database |
|---|---|---|
| Hematological | Tissue plasminogen activator, streptokinase, activated factor VII, granulocyte colony-stimulating factor, granulocyte–macrophage colony-stimulating factor, erythropoietin, romiplostim, hirudin, CBLB502, and CBLB612 | 33% |
| Musculoskeletal | Teriparatide, abaloparatide, salmon calcitonin, and amylin | 13.3% |
| Cardiopulmonary | Nesiritide, angiotensin II, and vasopressin | 10% |
| Metabolic | Insulin, glucagon, and dasiglucagon | 10% |
| Antimicrobial | Daptomycin, PL-18, and teicoplanin | 10% |
| Gastrointestinal | Linaclotide, interleukin-11, and TP508 | 10% |
| Analgesic | Leptucin and ziconotide | 6.7% |
| Central nervous system | Delta sleep-inducing peptide and interleukin-18-binding protein | 6.7% |
Categorical breakdown of identified peptide drugs with indications relevant to deep-space missions.
TABLE 2
| Pharmaceutical name | Common/Brand name | Function/Mechanism | Drug class | FDA approval (as of 07/2025) and indications | Shelf life and storage conditions | NASA interest | # Amino acid | Prior transgenic production | Source |
|---|---|---|---|---|---|---|---|---|---|
| Tissue plasminogen activator (tPA) | Alteplase, reteplase, and tenecteplase | Dissolution of blood clots | Thrombolytic agent | Approved for stroke and ST elevation myocardial infarction (STEMI) | 12 months at −20 °C or 3 weeks at room temperature | Emergency dissolution of blood clots | 355–527 | Yes [e.g., E. coli, B. subtilis, P. pastoris, and Chinese hamster ovary (CHO) cells] | ; ; Qiu et al., 1998; ; ; |
| Streptokinase | Kabikinase and Streptase | Originally approved for STEMI, NSTEMI, unstable anginas, pulmonary embolism, deep-vein thrombosis, arterial thrombosis or embolism, and occlusion of arteriovenous cannulae | Thrombolytic agent | No longer commercially available | 36 months unopened at 20 °C–25 °C | Emergency dissolution of blood clots | 440 | Yes (e.g., E.coli and S. pyogenes) | ; ; ; eMC database |
| Activated factor VII | Coagulation factor VIIa (recombinant)–jncw or SEVENFACT NOVOSEVEN | Blood clotting factor for hemorrhage | Clotting factor | Approved for bleeding episodes and prevention in surgical procedures on hemophiliacs | 36 months in desiccated form and stored below 25 °C | Sudden bleeding episodes | 406 | Yes [e.g., Leishmania, Spodoptera frugiperda, and baby hamster kidney (BHK) cells] | ; Wishart et al., 2006; ; ; ; European Medicines Agency database |
| Granulocyte colony-stimulating factor (G-CSF) | Lenograstim, filgrastim, Neupogen, and Neulasta | Stimulates the production of granulocytes | Colony-stimulating factor | Approved for neutropenia | 12 months when stored at −20 °C to −80 °C | Treatment of radiation-induced neutropenia, particularly in the lungs | 175 | Yes (e.g., E. coli, B. subtilis, and S. cerevisiae) | ; ; Trinh et al., 2021; Skokowa et al., 2022; |
| Granulocyte–macrophage colony-stimulating factor (GM-CSF) | Sargramostim (Leukine) Molgramostim (Molgradex) | Stimulates proliferation and differentiation of hematopoietic progenitor cells | Colony-stimulating factor | Sargramostim approved for post-chemotherapy, post-blood or post-bone-marrow transplantation and for acute radiation syndrome | 12 months stored at −20 °C to −80 °C or 1 month at 2 °C–8 °C | Treatment of radiation-induced lung injury | 127 | Yes (e.g., E. coli and P. pastoris) | ; U.S. Food and Drug Administration, 2018; Pykhtina et al., 2022; |
| Erythropoietin | Epoetin alfa, Epogen, and Procrit | Stimulates production of erythrocytes and erythrocyte precursors in the bone marrow | Hematopoietic growth factor | Approved for treatment of anemia | 18 months with refrigeration (2 °C–8 °C) | Treatment of acute radiation syndrome | 165 | Yes (e.g., CHO cells, E. coli, and C. reinhardtii) | ; ; Susantad et al., 2021; eMC database |
| Romiplostim | Nplate | Increases platelet and megakaryocyte production | Thrombopoietin receptor agonist/colony-stimulating factor | Approved for thrombocytopenia | 36 months at 2 °C–8 °C, protected from light 30 days at RT 24 h once reconstituted | Treatment of radiation-induced thrombocytopenia | 528 (2 identical single-chain subunits of 269 | Yes (e.g., E. coli) | ; ; Yang, 2015; PubChem database |
| Hirudin | Lepirudin and Refludan | Inhibits coagulant activity of thrombin | Thrombin inhibitor | Discontinued. Was originally FDA-approved as an anticoagulation in patients with heparin-associated thrombocytopenia (HIT) and associated thromboembolic disease | 36 months unopened at 20 °C–25 °C. Do not freeze or do not store over 25 °C. Use immediately after reconstitution | Sudden bleeding episodes | 65 | Yes (e.g., E. coli, S. cerevisiae, and P. pastoris) | Zhang and Lan, 2018; PubChem database; European Medicines Agency database |
| CBLB502 | Entolimod | Reduces radiation-induced apoptosis and accelerates the regeneration of progenitors in radiation-damaged tissues | Toll-like receptor (TLR) 5 agonist | Not FDA-approved, phase II clinical trials | Not available | Use for acute radiation syndrome. Protect hematopoietic and GI systems and stimulate regeneration | 329 | Yes (e.g., E. coli) | Ye et al., 2018; ; Singh and Seed, 2021; NCT02715882 |
| CBLB612 | N/A | Inhibits growth hormone receptor, potentially inhibiting growth and proliferation of cancer cells | TLR 2 agonist | Not FDA-approved, phase II clinical trials | Not available | Use for acute radiation syndrome | 9 | No | Yang et al., 2021; NCT02778763 |
| Teriparatide | Forteo | Stimulates bone formation through the stimulation of osteoblastic activity | Parathyroid hormone analog | Yes, for treatment of osteoporosis | 24 months unopened at 4 °C–8 °C 28 days once opened at 4 °C–8 °C | Counteract loss of bone density due to microgravity | 34 | Yes (e.g., E. coli and B. subtilis) | ; Vallota-Eastman et al., 2023; ; PubChem database |
| Abaloparatide | Tymlos | Stimulates osteoblast activity, increasing bone density | Parathyroid hormone analog | Yes, for treatment of osteoporosis | 36 months at 2 °C–8 °C | Counteract loss of bone density due to microgravity | 34 | Yes (e.g., E. coli) | Wang et al., 2014; PubChem database; European Medicines Agency database |
| Salmon calcitonin | Miacalcic calcitonin | Decreases osteoclast activity and thereby bone resorption. Stimulates calcium salt deposition in bone | Calcitonin | Yes, for postmenopausal osteoporosis, hypercalcemia, and Paget’s disease | 60 months unopened under refrigeration (2 °C–8 °C) | Counteract loss of bone density due to microgravity | 32 | Yes (e.g., E. coli) | ; Novartis, 2014; |
| Amylin | IAPP | Decreases bone resorption and increases osteoblast formation | Hormone | No. Clinical studies in progress | Not available | Counteract loss of bone density due to microgravity | 37 | Yes (e.g., E. coli) | ; ; NCT06186063 |
| Nesiritide | Natrecor | Regulates cardiovascular homeostasis through vasoconstriction | Natriuretic peptide | Discontinued, originally FDA-approved for acutely decompensated heart failure | 48 months at 15 °C–30 °C Reconstituted solution must be used within 24 h and stored between 2 °C and 25 °C | Use for emergency cases of heart failure | 32 | Yes (e.g., E. coli) | Scios Inc, 2001; Rao et al., 2011; Health Canada database |
| Angiotensin II | Giapreza | Increases blood pressure through vasoconstriction, fluid reabsorption, and release of aldosterone | Vasopressor | Yes, for low blood pressure with septic or distributive shock | 36 months for unopened vial at 2 °C–8 °C One diluted, 24 h at room temperature or refrigeration (2 °C–8 °C) | Use for hypotension due to head trauma or other causes including dehydration | 8 | Yes, for the precursor ovine ANG (e.g., E. coli and P. pastoris) | Yamashita et al., 2016; Palanikuma et al., 2019; European Medicines Agency database |
| Vasopressin (ADH) | Vasostrict | Increases blood pressure through vasoconstriction and fluid reabsorption | Vasopressor | Yes, to increase blood pressure in patients with vasodilatory shock | 12 months at 20 °C–25 °C, 24 months at 2 °C–8 °C. Once diluted, 18 h at room temperature, or 24 h under refrigeration | Use for hypotension due to head trauma or other causes including dehydration | 9 | Yes (e.g., cell-free wheat germ system) | ; Sterns, 2020; ; Novus Biologicals, 2025 |
| Linaclotide | Linzess | Increases secretion of solutes into intestinal lumen, resulting in increased secretion and softer stool | Guanylate cyclase C-agonists | Yes, for constipation and irritable bowel syndrome | 24–36 months unopened at 20 °C–25 °C 18 weeks after opening | Change in diet, environment, and stress may cause constipation. Previous astronauts have reported constipation | 14 | Yes | Thomas and Allmond, 2013; ; ; European Medicines Agency database; patent # WO2016038497A1 |
| Interleukin-11 (IL-11) | Neumega (oprelvekin) | Stimulates the production of hematopoietic stem cells, resulting in increased platelet production | Thrombopoietic growth factor | Discontinued. Originally FDA-approved for prevention of severe thrombocytopenia and reduction in the need for platelet transfusions following myelosuppressive chemotherapy | 24 months at 2 °C–8 °C | Radiation protection, particularly for the gut | 180 (recombinant version) | Yes (e.g., E. coli, P. pastoris, and S. cerevisiae) | ; ; patent # US20210317500A1; Drugs.com database |
| Rusalatide acetate (TP508) | Chrysalin | Activates radioresistant stem cells and increases the stemness potential of crypts to maintain and restore intestinal integrity | Regenerative peptide | No, phase II clinical trials for radiation-induced gastrointestinal damage | 72 months at −20 °C | Mitigate radiation-induced intestinal and colonic toxicity post-radiation exposure | 23 | No | Ryaby et al., 2006; ; ; NCT00131482; patent # WO2020210087A1 |
| Insulin | Lantus, Humalog, and Tradjenta | Transports glucose and potassium from the blood into cells | Hormone | Yes, for glycemic control in patients with diabetes | 12 months with refrigeration (4 °C–6 °C) | Treatment of hyperkalemia, which may arise due to conditions such as renal failure | 51 | Yes (e.g., E. coli, S. cerevisiae, and B. subtilis) | ; ; U.S. Food and Drug Administration, 2017; |
| Glucagon | GlucaGen | Increases blood glucose by promoting glycogenolysis and gluconeogenesis | Glucose-elevating agent and hormone | Yes, for hypoglycemia in diabetic patients | 24 months at room temperature | Necessary precaution if insulin is to be carried | 29 | Yes (e.g., E. coli) | ; Novo Nordisk Medical, 2025; PubChem database |
| Dasiglucagon | Zegalogue | Increases blood glucose by promoting glycogenolysis and gluconeogenesis | Glucose-elevating agent and hormone | Yes, for hypoglycemia in diabetic patients | 12 months at room temperature | Necessary precaution if insulin is to be carried | 29 | Information regarding production unavailable | Rechon Life Science AB, 2021; ; PubChem database |
| Delta sleep-inducing peptide | DSIP and Emideltide | Increases the production of GABA, slowing brain activity, inducing relaxation, and promoting deeper sleep | Neuromodulator | Not FDA-approved | 12 months at −80 °C 1 month at 2 °C–8 °C | Use to promote sleep—on orbit, sleep problems are common and may detriment health and performance | 9 | Yes (e.g., E. coli and P. pastoris) | Oh et al., 2003; ; |
| IL-18 binding proteins (IL-18 BP) | Tadekinig alfa | Inhibits IL-18, the key protein in radiation-induced cell and tissue damage and dysfunction | Immunoglobulin | Not FDA-approved. Phase III trials | 6 months below −70 °C Post-reconstitution 1 week at 4 °C or 3 months at −20 °C | Use for radioprotection | 164 | Yes (e.g., E. coli) | ; ; ; NCT03113760 |
| Leptucin | Leptucin | May act on supraspinal sites and spinal opioid receptors (being investigated) | Analgesic | Not FDA-approved. In the pre-clinical stage | Not available | Use to treat acute pain | 76 | No | |
| Ziconotide | Prialt | Selectively blocks N-type calcium channels on nociceptive afferent nerves | Analgesic | Yes, for severe chronic pain management | 48 months at 2–8 °C. 24 h once reconstituted at 2 °C–8 °C | Treatment of chronic pain | 25 | No | eMC database; PubChem database |
| Daptomycin | Cubicin | Inhibits bacterial cell wall integrity, along with DNA and RNA synthesis | Antibiotic | Yes, for Gram-positive bacterial skin infections | 36 months at 2 °C–8 °C. 12–48 h once reconstituted | Antimicrobials may be useful as astronauts may have a weakened immune system in space | 13 | Yes (e.g., S. lividans) | Penn et al., 2006; Tzotzos, 2016; ; eMC database |
| PL-18 | N/A | May inhibit quorum sensing, disrupt metabolic processes, and prevent biofilm formation (being investigated) | Antimicrobial and antifungal | No. Phase I trials | Not available | Use for vaginal tract infections; hygiene challenges of spaceflight may increase incidence of such infections | 15 | No | ; Rossino et al., 2023; Schlichter Kadosh et al., 2024; NCT05340790; patent # EP2735570B1 |
| Teicoplanin | Targocid | Prevents formation of peptidoglycan, inhibiting bacterial cell wall synthesis | Antibiotic | No. Approved in Europe for Gram-positive bacterial skin infections | 36 months when stored at 20 °C–25 °C in powder form 24 h once reconstituted and under refrigeration | Antimicrobials may be useful as astronauts may have a weakened immune system in space | 7 (within the core structure) | No | ; Vimberg, 2021; Sanofi, 2019 |
The database of 30 peptide-based drugs with pharmaceutical names, function, drug class, FDA approval status and indication, shelf life and storage, NASA interest, amino acid length, and a review of prior transgenic production.
As summarized in Table 1, hematological drugs that generally treat conditions related to the blood, bone marrow, or the body’s hemostatic mechanisms constitute 33% of the database. The identified hematological peptides can help mitigate the risks of radiation-induced blood conditions, such as neutropenia, blood clots, and sudden bleeding episodes during deep space missions. Peptides in the musculoskeletal category represent ∼13% of the database, with indications for mitigating microgravity-induced bone loss. Cardiopulmonary, metabolic, antimicrobial, and gastrointestinal drug categories each make up 10% of the database. Finally, peptides in the analgesic and central nervous system categories constitute ∼7% of the database each. Overall, the drug categories represented in the database align with the major risks to astronauts’ health during deep-space missions.
The majority (21/30) of the identified peptides in Table 2 are <100 amino acids long, with only four peptides exceeding 200 amino acids and all being <550 amino acids long (Figure 3A). It is important to note that their small size does not necessarily correlate with ease of recombinant expression. For example, small peptides can be prone to proteolytic degradation when expressed in microbial host systems (). Nevertheless, the majority (24/30) of the identified peptides have been recombinantly produced (Figure 3B). Our review of recombinant production focused on microbes, such as Escherichia coli or Bacillus subtilis, and yeast as host organisms as these systems are better suited for on-demand production in deep space due to a simpler process (compared to mammalian hosts) and the ability to transport some of these host organisms as durable spores. One limitation of microbial systems is their limited ability for post-translational modifications. Although human peptides and proteins commonly contain post-translational modifications, these are not always necessary for bioactivity. A remarkable example of this is filgrastim, an FDA-approved recombinant human granulocyte colony-stimulating factor (G-CSF) that was successfully produced in E. coli without glycosylation (Welte et al., 1996). Additionally, progress has been made to engineer prokaryotic glycosylation pathways into microbes (Valderrama-Rincon et al., 2012; Palma et al., 2024). Overall, the examples of recombinant production in microbes or yeast that we identified for the majority of the peptides in the database demonstrate the potential utility of a microbial-based system for on-demand pharmaceutical peptide production in deep space.
FIGURE 3
We demonstrated the expression of two peptides identified in Table 2, teriparatide and G-CSF, in B. subtilis (Vallota-Eastman et al., 2023). Our initial analysis focused on the need for G-CSF to treat severe neutropenia (low white blood count), a potentially severe medical condition that can result from a solar particle event (SPE) (). SPEs are unpredictable and can deliver a dose of radiation that is sufficient to cause severe neutropenia. To restore white blood cell count and prevent a possibly life-threatening infection, G-CSF would need to be administered within the first 3 days. highlighted that FDA-approved drugs for the treatment of neutropenia on Earth, such as G-CSF, could be life saving for the crew in deep space and, thus, should be considered for future medical toolkits.
Although we could not identify the recommended storage conditions and shelf life for five peptides that are in pre-clinical or early clinical trial stages, the majority of the peptides (17/30) require refrigeration or freezing for long-term storage (Figure 3C). Under recommended storage conditions, the average shelf life of the identified peptides (except the five where shelf-life information was not available) is ∼30 months, which is the expected duration of a long-term mission on the Martian surface (Figure 4A). However, refrigeration and freezing capabilities are likely to be limited during deep-space travel due to up-mass, volume, and power constraints. When these drugs cannot be stored refrigerated or frozen as recommended, the shelf life decreases dramatically, often from years to mere weeks (Table 3). The shelf life may also be further reduced due to the spaceflight environment (e.g., radiation) and if the drugs are removed from their original packaging. Additionally, the shelf life can be greatly reduced once a drug is opened or reconstituted, even when continued to be stored under recommended conditions.
FIGURE 4
TABLE 3
| Small-peptide drugs | Shelf life when frozen or refrigerated (as indicated) | Shelf life at room temperature (unless specified) | Decrease in shelf life |
|---|---|---|---|
| Tissue plasminogen activator | 12 months | 21 days | 94.2% |
| Erythropoietin | 18 months | 3 days | 99.5% |
| Insulin | 12 months | 28 days | 92.3% |
| Abaloparatide | 36 months | 30 days | 97.3% |
| Vasopressin | 24 months | 365 days | 50% |
| Ziconotide | 48 months | 60 days (at 37 °C) | 95.9% |
| Romiplostim | 36 months | 30 days | 97.3% |
Changes in shelf life when drugs are moved from sub−8 °C storage to room temperature (20 °C–25 °C). This table included drugs listed in Table 2 for which cold storage is recommended but for which information on room-temperature shelf life is also available.
When shelf life and recommended storage conditions are considered together, peptide drugs that expire before the planned return to Earth and require refrigeration or freezing would be impractical for deep-space missions, even if they are proven safe and effective in space and would, therefore, be ideal candidates for on-demand production using the Astropharmacy platform. Twelve of the peptides identified as potentially suitable for space meet these shelf life and storage criteria, including four hematological, three metabolic, two central nervous system, and one from each of the musculoskeletal, cardiopulmonary, and gastrointestinal drug categories (Figure 4B). As humans undertake long-duration interplanetary crewed missions, on-demand, on-site production may become the only option for providing pharmaceuticals to mitigate health risks.
3.3 Database limitations, utility, and future direction
It should be noted that the presented database is not an exhaustive list of useful peptide drugs for deep space, but rather a foundational list that is designed to be dynamic and built upon. To identify additional pharmaceutical peptides of interest for the database, a systematic review of all approved peptide drugs, followed by cross-referencing their indications with the identified human health risks in deep space (e.g., as identified by the Human Research Program), would be beneficial. One of the challenges encountered in generating the database is that some peptide drugs have multiple commercial alternatives, which may vary in shelf lives, storage conditions, and amino acid sequences. Additionally, we were unable to locate storage and shelf-life information for some of the identified peptides.
Although the database currently only includes peptide-based drugs, the addition of recombinant monoclonal antibodies (mAbs) could be explored in the future. The number of mAb treatments has sharply increased in recent years (), and mAbs have the potential to treat several conditions, from infectious diseases to osteoporosis. Furthermore, mAbs provide useful diagnostic capabilities by detecting biomarkers for various diseases or identifying the presence of events such as a heart attack (Quinteros et al., 2017). Currently, recombinant mAbs are mainly produced in mammalian cells, which provide the proper folding and glycosylation patterns. However, antibody fragments, which do not require the same post-translational modifications as full antibodies, have been produced in B. subtilis. These antibody fragments can have the same binding capacity as full antibodies, allowing for their clinical use (). Although the clinical efficacy of antibody fragments and their production in bacterial host systems is still being studied, integrating mAbs or antibody fragments into the Astropharmacy platform could open the door to a wider variety of therapeutics and diagnostic molecules available to astronauts. In addition to mAbs, the database and Astropharmacy capabilities can be expanded to include other “natural product” agents, for example, penicillin family antibiotics, antifungal agents, and some chemo agents.
Although Artificial Intelligence (AI) was not used in the production of this database, it could be a valuable tool in the future. AI could help comb through massive amounts of the literature and datasets to help identify drugs to add to the database, along with providing information such as drug stability and recombinant production capability. Importantly, AI models could be created to help predict the challenges of producing specific biologics in the database. A peptide production “difficulty estimate” could be generated from historical information from production trials, including details on peptide size, post-translational modifications, and integration of genetic and metabolic characteristics of the host expression system. Additionally, AI could be used to streamline the overall format, readability, and “look” of the database, optimizing it for users.
4 Conclusion
The medical kits onboard the ISS are composed of first-aid supplies and medications that target common ailments. Although these medications will still be needed on deep-space missions, there will also be a need for pharmaceutical countermeasures to address the unique health risks associated with deep-space travel. To our knowledge, this is the first study to compile a list of pharmaceutical peptides and proteins that have been used on Earth for the treatment of medical conditions that may also arise during deep-space missions. These peptides and proteins are commonly produced using recombinant organisms on Earth and thus have the potential to be produced on demand in deep space using platforms such as Astropharmacy. This could mitigate storage concerns and open the door for including peptide- and protein-based pharmaceuticals in the medicinal formulary for human deep-space missions. We aim to establish and demonstrate on-site, on-demand capabilities to produce the identified peptides using the Astropharmacy platform, whereas the compiled database can guide future research into the safety and efficacy of these peptides in space and serve as a useful resource for flight surgeons and those developing mission architectures for future human exploration of deep space.
Statements
Data availability statement
The original contributions presented in the study are included in the article/supplementary material; further inquiries can be directed to the corresponding author.
Author contributions
RB: Conceptualization, Methodology, Investigation, Writing – original draft. DO: Conceptualization, Methodology, Investigation, Writing – original draft. AK: Visualization, Writing – original draft. JS: Conceptualization, Visualization, Writing – review and editing. CB: Conceptualization, Investigation, Writing – review and editing. PW: Conceptualization, Methodology, Supervision, Writing – review and editing. DL: Conceptualization, Methodology, Supervision, Writing – review and editing. LR: Conceptualization, Methodology, Supervision, Writing – review and editing.
Funding
The author(s) declared that financial support was received for this work and/or its publication. This research was supported by the NASA Innovative Advanced Concepts (NIAC) program, funded by NASA’s Space Technology Mission Directorate. Phase II support was provided under proposal number 23-23NIACA2-P-0023, awarded through the 2023 NIAC Phase II Solicitation (80HQTR23NOA01-23NIAC-A2) for the project “A Flexible, Personalized, On-Demand Astropharmacy.” R.B. and D.O. were also supported by the NASA Rhode Island Space Grant Consortium’s Student Research Award in 2023 and 2024 and The Brown Undergraduate Teaching and Research Award in 2023.
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI statement
The author(s) declared that generative AI was not used in the creation of this manuscript.
Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
1
Abbexa (2025). Human Delta sleep-inducing peptide (dSIP) protein. Available online at: https://www.abbexa.com/human-dsip-protein.
2
AbbVie Inc (2024). Linzess (linacloride) capsules. Available online at: https://www.linzess.com/find-relief/how-to-take-linzess.
3
Acris Antibodies (2025). Recombinant human tissue plasminogen activator (TPA). Available online at: https://m1.acris-antibodies.com/pdf/PA1227_X_XC.pdf.
4
AfshinnekooE.ScottR. T.MacKayM. J.ParisetE.CekanaviciuteE.BarkerR.et al (2020). Fundamental biological features of spaceflight: advancing the field to enable deep-space exploration. Cell183 (5), 1162–1184. 10.1016/j.cell.2020.10.050
5
AghaeepoorM.AkbarzadehA.KobarfardF.ShabaniA. A.DehnaviE.Jamshidi AvalS.et al (2019). Optimization and high level production of recombinant synthetic streptokinase in E. coli using response surface methodology. Iran. Journal Pharmaceutical Research IJPR18 (2), 961–973. 10.22037/ijpr.2019.1100636
6
AkiyamaT.HorieK.HinoiE.HiraiwaM.KatoA.MaekawaY.et al (2020). How does spaceflight affect the acquired immune system?Npj Microgravity6 (1), 14. 10.1038/s41526-020-0104-1
7
Al ShaerD.Al MusaimiO.AlbericioF.de la TorreB. G. (2022). 2021 FDA TIDES (peptides and oligonucleotides) harvest. Pharmaceuticals15 (2), 222. 10.3390/ph15020222
8
American Regent Inc (2020). VASOPRESSIN. Available online at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212593s000lbl.pdf.
9
Amgen Inc (2008). Nplate (romiplostim). Available online at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/125268lbl.pdf.
10
AssiriA. S.El-GamalB. A.HafezE. E.HaidaraM. A. (2014). Production of recombinant streptokinase from Streptococcus pyogenes isolate and its potential for thrombolytic therapy. Saudi Medical Journal35 (12), 1482–1488. Available online at: http://www.ncbi.nlm.nih.gov/pubmed/25491213.
11
Australian Government (2008). Australian public assessment report (AUSPAR) for romiplostim. Available online at: https://www.tga.gov.au/sites/default/files/tga-bpi-pm-bpr-auspar-sample.pdf.
12
BaeC. S.YangD. S.LeeJ.ParkY. H. (1999). Improved process for production of recombinant yeast-derived monomeric human G-CSF. Appl. Microbiology Biotechnology52 (3), 338–344. 10.1007/s002530051529
13
BaeshenN. A.BaeshenM. N.SheikhA.BoraR. S.AhmedM. M. M.RamadanH. A. I.et al (2014). Cell factories for insulin production. Microb. Cell Factories13 (1), 141. 10.1186/s12934-014-0141-0
14
Bagheri-ZiariS.ShahbazzadehD.SardariS.SabatierJ. M.Pooshang BagheriK. (2021). Discovery of a new analgesic peptide, leptucin, from the Iranian scorpion, hemiscorpius lepturus. Molecules26 (9), 2580. 10.3390/molecules26092580
15
BarchettiK.DerobertmasureA.BoutouyrieP.SestiliP. (2024). Redefining space pharmacology: bridging knowledge gaps in drug efficacy and safety for deep space missions. Front. Space Technol.5, 1456614. 10.3389/frspt.2024.1456614
16
BashirS.SadafS.AhmadS.AkhtarM. W. (2015). Enhanced and secretory expression of human granulocyte colony stimulating factor by Bacillus subtilis SCK6. BioMed Research International2015, 636249. 10.1155/2015/636249
17
Biotechne R&D Systems (2024). Recombinant human GM-CSF GMP. Available online at: https://resources.rndsystems.com/pdfs/datasheets/215-gmp.pdf?v=20250701.
18
BlueR. S.BayuseT. M.DanielsV. R.WotringV. E.SureshR.MulcahyR. A.et al (2019a). Supplying a pharmacy for NASA exploration spaceflight: challenges and current understanding. Npj Microgravity5 (1), 14. 10.1038/s41526-019-0075-2
19
BlueR. S.ChancellorJ. C.AntonsenE. L.BayuseT. M.DanielsV. R.WotringV. E. (2019b). Limitations in predicting radiation-induced pharmaceutical instability during long-duration spaceflight. Npj Microgravity5 (1), 15. 10.1038/s41526-019-0076-1
20
BPS Bioscience (2025). Human Interleukin-11 recombinant. Available online at: https://bpsbioscience.com/human-interleukin-11-recombinant-90176-a.
21
ButlerM. S.HendersonI. R.CaponR. J.BlaskovichM. A. T. (2023). Antibiotics in the clinical pipeline as of December 2022. J. Antibiotics76, 431–447. 10.1038/s41429-023-00629-8
22
CarnellL. S. (2019). Spaceflight medical countermeasures: a strategic approach for mitigating effects from solar particle events. Int. J. Radiat. Biol.97, S125–S131. 10.1080/09553002.2020.1820603
23
CarriotJ.MackrousI.CullenK. E. (2021). Challenges to the vestibular system in space: how the brain responds and adapts to microgravity. Front. Neural Circuits15, 760313. 10.3389/fncir.2021.760313
24
Cell Guidance Systems (2025). Recombinant human G-CSF. Available online at: https://www.cellgs.com/products/recombinant-human-g-csf.html.
25
Chrysalis Biotherapeutics (2024). TP508 (chrysalin) peptide technology. Available online at: https://chrysbio.com/tp508-peptide-technology/.
26
ClarkT. K. (2019). “Effects of spaceflight on the vestibular system,” in Handbook of space pharmaceuticals (Cham: Springer International Publishing), 1–39. 10.1007/978-3-319-50909-9_2-1
27
ComfortP.McMahonJ. J.JonesP. A.CuthbertM.KendallK.LakeJ. P.et al (2021). Effects of spaceflight on musculoskeletal health: a systematic review and meta-analysis, considerations for interplanetary travel. Sports Med.51 (10), 2097–2114. 10.1007/s40279-021-01496-9
28
CrucianB. E.ChoukèrA.SimpsonR. J.MehtaS.MarshallG.SmithS. M.et al (2018). Immune system dysregulation during spaceflight: potential countermeasures for deep space exploration missions. Front. Immunol.9, 1437. 10.3389/fimmu.2018.01437
29
de la TorreB. G.AlbericioF. (2023). The pharmaceutical industry in 2022: an analysis of FDA drug approvals from the perspective of molecules. Molecules28 (3), 1038. 10.3390/molecules28031038
30
DiazT. E.IvesE. C.LazareD. I.BucklandD. M. (2024). Expiration analysis of the international space station formulary for exploration mission planning. Npj Microgravity10 (1), 76. 10.1038/s41526-024-00414-3
31
DonnorT.SarkarS. (2023). Insulin- pharmacology, therapeutic regimens and principles of intensive insulin therapy. Endotext. Available online at: https://www.ncbi.nlm.nih.gov/books/NBK278938/.
32
DrakeB. G.WattsK. D. (2014). Human exploration of Mars design reference architecture 5.0, addendum #2. Available online at: https://ntrl.ntis.gov/NTRL/dashboard/searchResults/titleDetail/N160003093.xhtml.
33
DuB.DanielsV. R.VaksmanZ.BoydJ. L.CradyC.PutchaL. (2011). Evaluation of physical and chemical changes in pharmaceuticals flown on space missions. AAPS J.13 (2), 299–308. 10.1208/s12248-011-9270-0
34
EconomouN. J.ZentnerI. J.LazoE.JakoncicJ.StojanoffV.WeeksS. D.et al (2013). Structure of the complex between teicoplanin and a bacterial cell-wall peptide: use of a carrier-protein approach. Acta Crystallogr. Sect. D. Biol. Crystallogr.69 (4), 520–533. 10.1107/S0907444912050469
35
Eichler-StahlbergA.WeisheitW.RueckerO.HeitzerM. (2009). Strategies to facilitate transgene expression in Chlamydomonas reinhardtii. Planta229 (4), 873–883. 10.1007/s00425-008-0879-x
36
Eli Lilly (2008). FORTEO. Available online at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021318s015lbl.pdf.
37
Endo Inc (2025). Vasostrict (vasopressin inhection, USP). Available online at: https://www.vasostrictrtu.com/.
38
EppelmannK.DoekelS.MarahielM. A. (2001). Engineered biosynthesis of the peptide antibiotic bacitracin in the surrogate host Bacillus subtilis. J. Biol. Chem.276 (37), 34824–34831. 10.1074/jbc.M104456200
39
European Medicines Agency (2018). Withdrawal assessment report: entolimod TMC. Available online at: https://www.ema.europa.eu/en/documents/withdrawal-report/withdrawal-assessment-report-entolimod-tmc_en.pdf.
40
FengF.HuP.ChenL.TangQ.LianC.YaoQ.et al (2013). Display of human proinsulin on the Bacillus subtilis spore surface for oral administration. Curr. Microbiol.67 (1), 1–8. 10.1007/s00284-013-0325-6
41
GajewskaM. E.SritharanS. S.Santoni-RugiuE.BendstrupE. M. (2018). Autoimmune pulmonary alveolar proteinosis in an adolescent successfully treated with inhaled rhGM-CSF (Molgramostim). Respir. Medicine Case Reports23, 167–169. 10.1016/j.rmcr.2018.02.005
42
Garrett-BakelmanF. E.DarshiM.GreenS. J.GurR. C.LinL.MaciasB. R.et al (2019). The NASA twins study: a multidimensional analysis of a year-long human spaceflight. Science364 (6436), eaau8650. 10.1126/science.aau8650
43
GenScript (2025). IL-18 BP, human. Available online at: https://www.genscript.com/protein/Z03168-IL_18_BP_Human.html.
44
GoudemandJ. (1998). Recombinant activated factor VII: a new treatment for hemophilia. Transfus. Clinique Biol.5 (4), 260–265. 10.1016/S1246-7820(98)80404-7
45
GruninaT. M.DemidenkoA. V.LyaschukA. M.PoponovaM. S.GalushkinaZ. M.SobolevaL. A.et al (2017). Recombinant human erythropoietin with additional processable protein domains: purification of protein synthesized in Escherichia coli heterologous expression system. Biochem. Mosc.82 (11), 1285–1294. 10.1134/S0006297917110062
46
GuoZ.ZhouG.HuW. (2022). Carcinogenesis induced by space radiation: a systematic review. Neoplasia32, 100828. 10.1016/j.neo.2022.100828
47
GuoL.ChenX.ZengH.TianN.LuW.ZhangJ.et al (2023). Production of recombinant human long-acting IL-18 binding protein: inhibitory effect on ulcerative colitis in mice. Appl. Microbiol. Biotechnol.107 (23), 7135–7150. 10.1007/s00253-023-12806-8
48
GuptaU.BaigS.MajidA.BellS. M. (2023). The neurology of space flight; how does space flight effect the human nervous system?Life Sci. Space Res.36, 105–115. 10.1016/j.lssr.2022.09.003
49
HeidaryM.KhosraviA. D.KhoshnoodS.NasiriM. J.SoleimaniS.GoudarziM. (2018). Daptomycin. J. Antimicrob. Chemother.73 (1), 1–11. 10.1093/jac/dkx349
50
HongD.MingqiangZ.MinL.ChangqingC.JifangM. (2000). Production of recombinant salmon calcitonin by amidation of precursor peptide using enzymatic transacylation and photolysis in vitro. Biochem. Biophysical Res. Commun.267 (1), 362–367. 10.1006/bbrc.1999.1961
51
IshizakiJ.TamakiM.ShinM.TsuzukiH.YoshikawaK.TeraokaH.et al (1992). Production of recombinant human glucagon in the form of a fusion protein in escherichia coli; recovery of glucagon by sequence-specific digestion. Appl. Microbiol. Biotechnol.36 (4), 483–486. 10.1007/BF00170188
52
JilaniT. N.SiddiquiA. H. (2025). Tissue plasminogen activator. StatPearls. Available online at: http://www.ncbi.nlm.nih.gov/pubmed/18208365.
53
KalolaU. K.PatelP.ChowdhuryY. S. (2025). Linaclotide, StatPearls. Available online at: http://www.ncbi.nlm.nih.gov/pubmed/23198977.
54
KantaraC.MoyaS. M.HouchenC. W.UmarS.UllrichR. L.SinghP.et al (2015). Novel regenerative peptide TP508 mitigates radiation-induced gastrointestinal damage by activating stem cells and preserving crypt integrity. Lab. Investig.95 (11), 1222–1233. 10.1038/labinvest.2015.103
55
KhanM. W.MusgraveS. C.JenkinsN. (1995). “Production and post-translational modification of tissue plasminogen activator (tPA) in namalwa cells,” in Animal cell technology: developments towards the 21st century (Dordrecht: Springer Netherlands), 397–401. 10.1007/978-94-011-0437-1_63
56
KrampertM.BernhagenJ.SchmuckerJ.HornA.SchmauderA.BrunnerH.et al (2000). Amyloidogenicity of recombinant human pro-islet amyloid polypeptide (ProIAPP). Chem. and Biol.7 (11), 855–871. 10.1016/S1074-5521(00)00034-X
57
KrittanawongC.SinghN. K.ScheuringR. A.UrquietaE.BershadE. M.MacaulayT. R.et al (2022). Human health during space travel: state-of-the-art review. Cells12 (1), 40. 10.3390/cells12010040
58
KrittanawongC.IsathA.KaplinS.VirkH. U. H.FoggS.WangZ.et al (2023). Cardiovascular disease in space: a systematic review. Prog. Cardiovasc. Dis.81, 33–41. 10.1016/j.pcad.2023.07.009
59
KunitskayaA.PiretJ. M.BuckleyN.Low-DécarieE. (2022). Meta-analysis of health research data from greater than three months international space station missions. Acta Astronaut.201, 420–430. 10.1016/j.actaastro.2022.09.019
60
LakowitzA.KrullR.BiedendieckR. (2017). Recombinant production of the antibody fragment D1.3 scFv with different bacillus strains. Microb. Cell Factories16 (1), 14. 10.1186/s12934-017-0625-9
61
Lee SatcherR.FiedlerB.GhaliA.DirschlD. R. (2024). Effect of spaceflight and microgravity on the musculoskeletal system: a review. J. Am. Acad. Orthop. Surg.32 (12), 535–541. 10.5435/JAAOS-D-23-00954
62
LFBS. A. (2024). SEVENFACT. Available online at: https://www.fda.gov/vaccines-blood-biologics/sevenfact.
63
LiY. (2011). Recombinant production of antimicrobial peptides in escherichia coli: a review. Protein Expr. Purif.80 (2), 260–267. 10.1016/j.pep.2011.08.001
64
LiX.CuiW.HullL.WangL.YuT.XiaoM. (2020). IL-18 binding protein (IL-18BP) as a novel radiation countermeasure after radiation exposure in mice. Sci. Rep.10 (1), 18674. 10.1038/s41598-020-75675-5
65
Lin-FaW.HumW. T.KalyanN. K.LeeS. G.HungP. P.DoiR. H. (1989). Synthesis and refolding of human tissue-type plasminogen activator in Bacillus subtilis. Gene84 (1), 127–133. 10.1016/0378-1119(89)90146-7
66
LipiäinenT.PeltoniemiM.SarkhelS.YrjönenT.VuorelaH.UrttiA.et al (2015). Formulation and stability of cytokine therapeutics. J. Pharm. Sci.104 (2), 307–326. 10.1002/jps.24243
67
MahmudaA.BandeF.Kadhim Al-ZihiryK. J.AbdulhaleemN.MajidR. A.HamatR. A.et al (2017). Monoclonal antibodies: a review of therapeutic applications and future prospects. Trop. J. Pharm. Res.16 (3), 713. 10.4314/tjpr.v16i3.29
68
MasrooriN.HalabianR.MohammadipourM.RoushandehA. M.RouhbakhshM.NajafabadiA. J.et al (2010). High-level expression of functional recombinant human coagulation factor VII in insect cells. Biotechnol. Lett.32 (6), 803–809. 10.1007/s10529-010-0227-7
69
MazzeoA.CarpenterP. (2009). “Stability studies for biologics,” in Handbook of stability testing in pharmaceutical development (New York, NY: Springer New York), 353–369. 10.1007/978-0-387-85627-8_17
70
McLaughlinM. B.AwosikaA. O.JialalI. (2025). Calcitonin, StatPearls. Available online at: http://www.ncbi.nlm.nih.gov/pubmed/25182228.
71
Medical Operations Directorate and Operations Division (2001). International space station integrated medical group (IMG) medical checklist. NASA/JSC-48522-E4.
72
Medicines Management Programme (2024). Best-value medicine (teriparatide): tetridar. Available online at: https://www.hse.ie/eng/about/who/cspd/medicines-management/best-value-medicines/teriparatide/bvm-tetridar-product-information-sheet.pdf.
73
MeermanM.Bracco GartnerT. C. L.BuikemaJ. W.WuS. M.SiddiqiS.BoutenC. V. C.et al (2021). Myocardial disease and long-distance space travel: solving the radiation problem. Front. Cardiovasc. Med.8, 631985. 10.3389/fcvm.2021.631985
74
MehtaP.BhayaniD. (2017). Impact of space environment on stability of medicines: challenges and prospects. J. Pharm. Biomed. Analysis136, 111–119. 10.1016/j.jpba.2016.12.040
75
MehtaH. M.MalandraM.CoreyS. J. (2015). G-CSF and GM-CSF in neutropenia. J. Immunol.195 (4), 1341–1349. 10.4049/jimmunol.1500861
76
MillerF. J.NiederhausC.BarlowK.GriffinD. (2007). “Intravenous solutions for exploration missions,” in 45th AIAA aerospace sciences meeting and exhibit (Reston, Virigina: American Institute of Aeronautics and Astronautics). 10.2514/6.2007-544
77
MirzaahmadiS.Asaadi-TehraniG.BandehpourM.DavoudiN.TahmasbiL.HosseinzadehN.et al (2011). Expression of recombinant human coagulation factor VII by the lizard Leishmania expression system. J. Biomedicine and Biotechnology2011, 873874. 10.1155/2011/873874
78
MohammadiE.Seyedhosseini-GhahehH.MahnamK.Jahanian-NajafabadiA.Mir Mohammad SadeghiH. (2019). Reteplase: structure, function, and production. Adv. Biomed. Res.8 (1), 19. 10.4103/abr.abr_169_18
79
MuX.QuL.YinL.WangL.LiuX.LiuD. (2024). Pichia pastoris secreted peptides crossing the blood-brain barrier and DSIP fusion peptide efficacy in PCPA-induced insomnia mouse models. Front. Pharmacol.15, 1439536. 10.3389/fphar.2024.1439536
80
MundadaL. V.ProrokM.DeFordM. E.FigueraM.CastellinoF. J.FayW. P. (2003). Structure-function analysis of the streptokinase amino terminus (residues 1–59). J. Biol. Chem.278 (27), 24421–24427. 10.1074/jbc.M301825200
81
NASA (2005). Medical kit - contents and reference. Available online at: https://www.nasa.gov/wp-content/uploads/2015/03/medical_kit_checklist_-_full_release.pdf.
82
NASA (2023). NASA-STD-3001 technical brief. Pharmaceutical care. Available online at: https://www.nasa.gov/wp-content/uploads/2023/03/pharmaceuticals-and-medications-tech-brief-ochmo.pdf.
83
NgoH. X.Garneau-TsodikovaS. (2018). What are the drugs of the future?MedChemComm9 (5), 757–758. 10.1039/C8MD90019A
84
NohD.BowerR. L.HayD. L.ZhyvoloupA.RaleighD. P. (2020). Analysis of amylin consensus sequences suggests that human amylin is not optimized to minimize amyloid formation and provides clues to factors that modulate amyloidogenicity. ACS Chemical Biology15 (6), 1408–1416. 10.1021/acschembio.9b01050
85
NorskP.AsmarA.DamgaardM.ChristensenN. J. (2015). Fluid shifts, vasodilatation and ambulatory blood pressure reduction during long duration spaceflight. J. Physiology593 (3), 573–584. 10.1113/jphysiol.2014.284869
86
Novartis (2014). MIACALCIN (calcitonin-salmon). Available online at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/017808s035lbl.pdf.
87
Novo Nordisk Medical (2025). GlucaGen analogues and insulins. Available online at: https://www.novonordiskmedical.com//product-information/storage-and-stability/glucagen-and-insulins.html.
88
Novus Biologicals (2025). Recombinant human V1a vasopressin R/AVPR1A GST (N-Term) protein. Available online at: https://www.novusbio.com/products/v1a-vasopressin-r-avpr1a-partial-recombinant-protein_h00000552-q01.
89
OhK.-S.DokyunN.KweonM.-H.SungH.-C. (2003). Expression and purification of delta sleep-inducing peptide in Escherichia coli. J. Microbiol. Biotechnol.13 (4), 620–623.
90
PalanikumarI.KatlaS.TaharaN.YuiM.ZhangR.EbiharaA.et al (2019). Heterologous expression, purification, and functional characterization of recombinant ovine angiotensinogen in the methylotrophic yeast Pichia pastoris. Biotechnol. Prog.35 (5), e2866. 10.1002/btpr.2866
91
PalmaJ. A.BunyatovM. I.HulbertS. W.JewettM. C.DeLisaM. P. (2024). Bacterial glycoengineering: cell-based and cell-free routes for producing biopharmaceuticals with customized glycosylation. Curr. Opin. Chem. Biol.81, 102500. 10.1016/j.cbpa.2024.102500
92
PatelZ. S.BrunstetterT. J.TarverW. J.WhitmireA. M.ZwartS. R.SmithS. M.et al (2020). Red risks for a journey to the red planet: the highest priority human health risks for a mission to Mars. Npj Microgravity6 (1), 33. 10.1038/s41526-020-00124-6
93
PennJ.LiX.WhitingA.LatifM.GibsonT.SilvaC. J.et al (2006). Heterologous production of daptomycin in streptomyces lividans. J. Industrial Microbiol. and Biotechnol.33 (2), 121–128. 10.1007/s10295-005-0033-8
94
PykhtinaM.MiroshnichenkoS.KulikovY.BeklemishevA. (2022). “Development bioactive of human recombinant GM-CSF produced in Pichia pastoris yeast,” in 2022 IEEE international multi-conference on engineering, computer and information sciences (SIBIRCON) (IEEE), 260–263. 10.1109/SIBIRCON56155.2022.10016782
95
QiuJ.SwartzJ. R.GeorgiouG. (1998). Expression of active human tissue-type plasminogen activator in Escherichia coli. Appl. Environ. Microbiol.64 (12), 4891–4896. 10.1128/AEM.64.12.4891-4896.1998
96
QuinterosD. A.BermudezJ. M.RavettiS.CidA.AllemandiD. A.PalmaS. D. (2017). “Therapeutic use of monoclonal antibodies: general aspects and challenges for drug delivery,” in Nanostructures for drug delivery (Elsevier), 807–833. 10.1016/B978-0-323-46143-6.00025-7
97
RaoL. S.NiphadkarM. P.PaliwalD.ShekhawatR.KhareA. G.UmaS.et al (2011). Expression, purification, and characterisation of nesiritide using an E. coli expression system. Biotechnol. Bioprocess Eng.16 (4), 688–697. 10.1007/s12257-010-0309-3
98
Rechon Life Science AB (2021). ZEGALOGUE. Available online at: https://www.zegalogue.com/content/dam/diabetes-patient/zegalogue/en/pdf/zegalogue-autoinjector-instruction-for-use.pdf.
99
ReichardJ. F.PhelpsS. E.LehnhardtK. R.YoungM.EasterB. D. (2023). The effect of long-term spaceflight on drug potency and the risk of medication failure. Npj Microgravity9 (1), 35. 10.1038/s41526-023-00271-6
100
RossinoG.MarcheseE.GalliG.VerdeF.FinizioM.SerraM.et al (2023). Peptides as therapeutic agents: challenges and opportunities in the green transition era. Molecules28 (20), 7165. 10.3390/molecules28207165
101
RyabyJ. T.ShellerM. R.LevineB. P.BramletD. G.LaddA. L.CarneyD. H. (2006). Thrombin peptide TP508 stimulates cellular events leading to angiogenesis, revascularization, and repair of dermal and musculoskeletal tissues. J. Bone Jt. Surg.88 (Suppl. l_3), 132–139. 10.2106/JBJS.F.00892
102
Sanofi (2019). Teicoplanin. Available online at: https://www.campus.sanofi/dam/jcr:d6cd874c-9dff-4757-b8df-3ea0f5e4b930/Targocid-Inj-PI.pdf.
103
Schlichter KadoshY.MuthuramanS.NisaaK.Ben-ZviA.Karsagi ByronD. L.ShaganM.et al (2024). Pseudomonas aeruginosa quorum sensing and biofilm attenuation by a di-hydroxy derivative of piperlongumine (PL-18). Biofilm8 (100215), 100215. 10.1016/j.bioflm.2024.100215
104
Scios Inc (2001). Natrecor (nesiritide). Available online at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/20920lbl.pdf.
105
ScullyR. R.MeyersV. E.JamesJ. T.Kahn-MayberryN. (2015). Risk of adverse health and performance effects of celestial dust exposure. Available online at: https://ntrs.nasa.gov/api/citations/20150016031/downloads/20150016031.pdf.
106
SeidlerR. D.MaoX. W.TaysG. D.WangT.Zu EulenburgP. (2024). Effects of spaceflight on the brain. Lancet Neurology23 (8), 826–835. 10.1016/S1474-4422(24)00224-2
107
Seoane-ViañoI.OngJ. J.BasitA. W.GoyanesA. (2022). To infinity and beyond: strategies for fabricating medicines in outer space. Int. J. Pharm. X4, 100121. 10.1016/j.ijpx.2022.100121
108
ShaghaghiZ.AlvandiM.NosratiS.HadeiS. K. (2021). Potential utility of peptides against damage induced by ionizing radiation. Future Oncol.17 (10), 1219–1235. 10.2217/fon-2020-0577
109
ShenM.FrishmanW. H. (2019). Effects of spaceflight on cardiovascular physiology and health. Cardiol. Rev.27 (3), 122–126. 10.1097/CRD.0000000000000236
110
SibongaJ.MatsumotoT.JonesJ.ShapiroJ.LangT.ShackelfordL.et al (2019). Resistive exercise in astronauts on prolonged spaceflights provides partial protection against spaceflight-induced bone loss. Bone128, 112037. 10.1016/j.bone.2019.07.013
111
SimonsenL. C.SlabaT. C.GuidaP.RusekA. (2020). NASA’s first ground-based galactic cosmic ray simulator: enabling a new era in space radiobiology research. PLOS Biol.18 (5), e3000669. 10.1371/journal.pbio.3000669
112
SinghV. K.SeedT. M. (2021). Entolimod as a radiation countermeasure for acute radiation syndrome. Drug Discov. Today26 (1), 17–30. 10.1016/j.drudis.2020.10.003
113
SkokowaJ.Hernandez AlvarezB.ColesM.RitterM.NasriM.HaafJ.et al (2022). A topological refactoring design strategy yields highly stable granulopoietic proteins. Nat. Commun.13 (1), 2948. 10.1038/s41467-022-30157-2
114
SternsR. H. (2020). “Water homeostasis in chronic kidney disease,” in Chronic renal disease (Elsevier), 615–632. 10.1016/B978-0-12-815876-0.00038-3
115
SusantadT.FuangthongM.TharakaramanK.Tit-OonP.RuchirawatM.SasisekharanR. (2021). Modified recombinant human erythropoietin with potentially reduced immunogenicity. Sci. Reports11 (1), 1491. 10.1038/s41598-020-80402-1
116
ThomasR. H.AllmondK. (2013). Linaclotide (linzess) for irritable bowel syndrome with constipation and for chronic idiopathic constipation. P and T A Peer-Reviewed Journal Formulary Management38 (3), 154–160. Available online at: http://www.ncbi.nlm.nih.gov/pubmed/23641133.
117
TomsiaM.CieślaJ.ŚmieszekJ.FlorekS.MaciongaA.MichalczykK.et al (2024). Long-term space missions’ effects on the human organism: what we do know and what requires further research. Front. Physiology15, 1284644. 10.3389/fphys.2024.1284644
118
TrinhN. T. M.ThuocT. L.ThaoD. T. P. (2021). Production of recombinant human G-CSF from non-classical inclusion bodies in Escherichia coli. Braz. Journal Microbiology Publ. Braz. Soc. Microbiol.52 (2), 541–546. 10.1007/s42770-020-00413-y
119
TzotzosS. J. (2016). Daptomycin - a new twist to an old tale. Available online at: https://www.eurpepsoc.com/wp-content/uploads/2016/12/Tzotzos_Dec_2016.pdf#:∼:text=Daptomycincontainsanumberof,andhasthesequence1WDNDTGODDADGDSmEKyn13.
120
U.S. Food and Drug Administration (2017). Information regarding insulin storage and switching between products in an emergency. Available online at: https://www.fda.gov/drugs/emergency-preparedness-drugs/information-regarding-insulin-storage-and-switching-between-products-emergency.
121
U.S. Food and Drug Administration (2018). FDA approves leukin for acute radiation syndrome. Available online at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/125268lbl.pdf.
122
Valderrama-RinconJ. D.FisherA. C.MerrittJ. H.FanY. Y.ReadingC. A.ChhibaK.et al (2012). An engineered eukaryotic protein glycosylation pathway in Escherichia coli. Nat. Chem. Biol.8 (5), 434–436. 10.1038/nchembio.921
123
Vallota-EastmanA.BuiC.WilliamsP. M.ValentineD. L.LoftusD.RothschildL. (2023). Bacillus subtilis engineered for aerospace medicine: a platform for on-demand production of pharmaceutical peptides. Front. Space Technol.4, 1181843. 10.3389/frspt.2023.1181843
124
VimbergV. (2021). Teicoplanin—A new use for an old drug in the COVID-19 era?Pharmaceuticals14 (12), 1227. 10.3390/ph14121227
125
WangH.LiuJ.YinY.WuJ.WangZ.MiaoD.et al (2014). Recombinant human parathyroid hormone related protein 1-34 and 1-84 and their roles in osteoporosis treatment. PloS One9 (2), e88237. 10.1371/journal.pone.0088237
126
WangL.WangN.ZhangW.ChengX.YanZ.ShaoG.et al (2022). Therapeutic peptides: current applications and future directions. Signal Transduct. Target. Ther.7 (1), 48. 10.1038/s41392-022-00904-4
127
WaniA.PrabhakarB.ShendeP. (2024). Strategic aspects of space medicine: a journey from conventional to futuristic requisites. Space Sci. and Technol.4, 0123. 10.34133/space.0123
128
WelteK.GabriloveJ.BronchudM. H.PlatzerE.MorstynG. (1996). Filgrastim (r-metHuG-CSF): the first 10 years. Blood88 (6), 1907–1929. 10.1182/blood.V88.6.1907.bloodjournal8861907
129
WishartD. S.KnoxC.GuoA. C.ShrivastavaS.HassanaliM.StothardP.et al (2006). DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res.34 (90001), D668–D672. 10.1093/nar/gkj067
130
WotringV. E. (2015). Medication use by U.S. crewmembers on the international space station. FASEB J.29 (11), 4417–4423. 10.1096/fj.14-264838
131
WotringV. E. (2016). Chemical potency and degradation products of medications stored over 550 Earth days at the international space station. AAPS J.18 (1), 210–216. 10.1208/s12248-015-9834-5
132
YamashitaS.ShibataN.Boku-IkedaA.AbeE.InayamaA.YamaguchiT.et al (2016). Escherichia coli-based production of recombinant ovine angiotensinogen and its characterization as a renin substrate. BMC Biotechnol.16 (1), 33. 10.1186/s12896-016-0265-x
133
YangA. S. (2015). Development of romiplostim: a novel engineered peptibody. Seminars Hematol.52 (1), 12–15. 10.1053/j.seminhematol.2014.10.007
134
YangH.PengT.WenX.ChenT.SunY.LiuS.et al (2021). A photolabile carboxyl protecting group for solid phase peptide synthesis. ChemistryOpen10 (4), 497–502. 10.1002/open.202000324
135
YeB.ShenW.ShiM.ZhangY.XuC.ZhaoZ. (2018). Intein-mediated backbone cyclization of entolimod confers enhanced radioprotective activity in mouse models. PeerJ6, e5043. 10.7717/peerj.5043
136
YinY.LiuJ.FanQ.ZhaoS.WuX.WangJ.et al (2023). Long-term spaceflight composite stress induces depression and cognitive impairment in astronauts—insights from neuroplasticity. Transl. Psychiatry13 (1), 342. 10.1038/s41398-023-02638-5
137
YuleS.RobertsonJ. M.MormannB.SminkD. S.LipsitzS.AbahujeE.et al (2023). Crew autonomy during simulated medical event management on long duration space exploration missions. Hum. Factors J. Hum. Factors Ergonomics Soc.65 (6), 1221–1234. 10.1177/00187208211067575
138
ZhangJ.LanN. (2018). Hirudin variants production by genetic engineered microbial factory. Biotechnol. Genet. Eng. Rev.34 (2), 261–280. 10.1080/02648725.2018.1506898
Summary
Keywords
space medicine, peptide medications, on-demand drug manufacturing, long-duration space missions, engineered microbes
Citation
Blum RC, Omrani D, Kunitskaya A, Snyder JE, Bui C, Williams PM, Loftus DJ and Rothschild LJ (2026) The database of peptide medications for human deep-space missions demonstrates the potential for on-demand “Astropharmacy”. Front. Space Technol. 6:1692554. doi: 10.3389/frspt.2025.1692554
Received
25 August 2025
Revised
13 October 2025
Accepted
24 December 2025
Published
24 February 2026
Volume
6 - 2025
Edited by
Rowena Christiansen, The University of Melbourne, Australia
Reviewed by
Ilaria Cinelli, Aerospace Medical Association, United States
Priya Patel, Saurashtra University, India
Updates
Copyright
© 2026 United States Government as represented by the Administrator of the National Aeronautics and Space Administration and Rebecca C. Blum, Dorra Omrani, Dr. Alina Kunitskaya, Dr. Jessica E. Snyder, Cynthia Bui, and Dr. Philip M. Williams. At least a portion of this work is authored by Dr. Lynn J. Rothschild and Dr. David J. Loftus on behalf of the U.S. Government and, as regards Dr. Rothschild and Dr. Loftus, U.S. copyright protection does not attach to separable portions of a Work authored solely by U.S. Government employees as part of their official duties. The U.S. Government is the owner of foreign copyrights in such separable portions of the Work and is a joint owner (with any non-U.S. Government author) of U.S. and foreign copyrights that may be asserted in inseparable portions the Work. The U.S. Government retains the right to use, reproduce, distribute, create derivative works, perform, and display portions of the Work authored solely or co-authored by a U.S. Government employee. Non-U.S. copyrights also apply.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Alina Kunitskaya, alinakunitskaya@gmail.com
† These authors have contributed equally to this work and share first authorship
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.