Polypharmacology is a research ‘hotspot’ at the intersection of medicinal chemistry, structural biology, clinical pharmacology, and molecular medicine. Having evolved from the specificity paradigm, it is generally accepted that drugs mostly exert their biological effects not by the sole interaction with one singular, defined target but by multiple individual interactions with multiple targets. This ‘multitarget paradigm’ particularly anticipates multiple interactions of drugs, often designated as multitargeting or promiscuity. From a clinical perspective, polypharmacological drugs provide an opportunity for additive or even synergistic biological effects. Thus, their unique polypharmacological profiles enable greater therapeutic benefit for patients.
One important field in polypharmacology is drug repurposing – the exploration of novel therapeutic indications for drugs already on the market. Through broad assessment in various in vitro assays and in vivo models, the polypharmacological profiles of these drugs can be uncovered, turning off-target effects from so-called dirty drugs into new clinical applications. Besides reducing drug development costs and approval processing times, this broad assessment, also referred to as drug profiling, increases data awareness and general safety while also reducing the risk for drug-drug interactions and the development of drug resistance mechanisms – turning drug annotation into actual medicinal meaning.
Another very important field in polypharmacology is target repurposing (also called target fishing) – the exploration of novel undruggable targets exploiting the knowledge accumulated with respect to phylogenetically and/or functionally related proteins or protein (super)families. By elucidating compound-based target relationships as well as protein structure similarity clusters, ligand- and structure-based approaches facilitate the drug development process.
ABC and SLC transporters fulfil important physiological functions, and dysregulation as well as genetic deficiency of most members are associated with both highly prevalent and orphan diseases. Beyond their biological function as mediators of solutes (as well as drugs) between (sub-)cellular compartments, ABC and SLC transporters constitute a remote communication network in which a role in signal transduction (‘transceptor’) has been suggested. Many of these transporters cannot or only barely be addressed by small-molecule ligands. Thus, their pathophysiology remains unclear to this date.
This Research Topic is intended to collect latest and high-class original research and review reports that complement and advance the chart of chemical, target, and bioactivity space in network polypharmacology of ABC and SLC transporters. Manuscripts from all disciplines are welcome, particularly from computational chemistry (molecular modelling, virtual screening, etc.), bioinformatics (big data, data analysis, etc.), structural biology (x-ray, cryo-EM, etc.), medicinal chemistry (hit identification, hit-to-lead optimisation, etc.), molecular pharmacology (functional assays, expression analysis, etc.) as well as molecular genomics (genome-wide association studies, genetic variant studies, etc.) and other multidisciplinary concepts. This will support network control, promote basic understanding, advance drug development, and ultimately lead to greater clinical success.
Polypharmacology is a research ‘hotspot’ at the intersection of medicinal chemistry, structural biology, clinical pharmacology, and molecular medicine. Having evolved from the specificity paradigm, it is generally accepted that drugs mostly exert their biological effects not by the sole interaction with one singular, defined target but by multiple individual interactions with multiple targets. This ‘multitarget paradigm’ particularly anticipates multiple interactions of drugs, often designated as multitargeting or promiscuity. From a clinical perspective, polypharmacological drugs provide an opportunity for additive or even synergistic biological effects. Thus, their unique polypharmacological profiles enable greater therapeutic benefit for patients.
One important field in polypharmacology is drug repurposing – the exploration of novel therapeutic indications for drugs already on the market. Through broad assessment in various in vitro assays and in vivo models, the polypharmacological profiles of these drugs can be uncovered, turning off-target effects from so-called dirty drugs into new clinical applications. Besides reducing drug development costs and approval processing times, this broad assessment, also referred to as drug profiling, increases data awareness and general safety while also reducing the risk for drug-drug interactions and the development of drug resistance mechanisms – turning drug annotation into actual medicinal meaning.
Another very important field in polypharmacology is target repurposing (also called target fishing) – the exploration of novel undruggable targets exploiting the knowledge accumulated with respect to phylogenetically and/or functionally related proteins or protein (super)families. By elucidating compound-based target relationships as well as protein structure similarity clusters, ligand- and structure-based approaches facilitate the drug development process.
ABC and SLC transporters fulfil important physiological functions, and dysregulation as well as genetic deficiency of most members are associated with both highly prevalent and orphan diseases. Beyond their biological function as mediators of solutes (as well as drugs) between (sub-)cellular compartments, ABC and SLC transporters constitute a remote communication network in which a role in signal transduction (‘transceptor’) has been suggested. Many of these transporters cannot or only barely be addressed by small-molecule ligands. Thus, their pathophysiology remains unclear to this date.
This Research Topic is intended to collect latest and high-class original research and review reports that complement and advance the chart of chemical, target, and bioactivity space in network polypharmacology of ABC and SLC transporters. Manuscripts from all disciplines are welcome, particularly from computational chemistry (molecular modelling, virtual screening, etc.), bioinformatics (big data, data analysis, etc.), structural biology (x-ray, cryo-EM, etc.), medicinal chemistry (hit identification, hit-to-lead optimisation, etc.), molecular pharmacology (functional assays, expression analysis, etc.) as well as molecular genomics (genome-wide association studies, genetic variant studies, etc.) and other multidisciplinary concepts. This will support network control, promote basic understanding, advance drug development, and ultimately lead to greater clinical success.
