About this Research Topic
Thus, to-date, CNS disorders present a huge unmet medical need that without disease-modifying treatments will create an increasingly heavy burden on the global health system. The human brain is uniquely complex, and the blood-brain barrier presents a protection system that presents a major challenge for medicinal chemists working in the CNS discovery space. Indeed, in the cases of Parkinson’s and Alzheimer’s disease, few novel treatments have obtained approval for clinical use. Challenging chemical properties required for CNS drug exposure and the complex pathologies of CNS disorders create a challenging task of identifying novel, high impact drug targets. With the CNS therapeutics market valuation of >$100 billion in 2022, the challenge of creating efficient disease modifying therapies for CNS disorders remains extreme, and thus experts in all areas of small molecule CNS drug development are welcomed to contribute to this research topic, to highlight the state-of-the-art approaches and to report their recent achievements in drug design and development.
The Research Topic aims to collect several article types (see below), that disclose and discuss the most recent advances and challenges in the discovery of CNS penetrant small molecules. Furthermore, we welcome articles that present the discovery of small molecules presenting novel pharmacology such as allosteric modulators, splicing modulators and protein degraders. Research that describes the utilization of different in silico approaches such as ligand-based and structure-based drug design are also highly encouraged. Moreover, development of chemical biology and/or chemical probes used to identify and validate CNS drug targets are welcome.
The manuscripts of interest (Original research, Reviews, Mini Reviews, Perspective, Opinion and Editorial) may include, but are not limited to:
• Development and Biological Evaluation of novel small molecules targeting CNS disorders.
• Development of novel small molecule approaches are of particular interest e.g. allosteric modulators, molecular glues, PROTACS and other protein degradation technologies.
• Computer-Aided Drug Design and in silico Identification of small molecules, supported by experimental validation.
• CNS Drug delivery modalities e.g. prodrugs, formulations and medicinal chemistry strategies to improve chemical properties and exposure.
• Chemical biology approaches to identifying novel CNS drug targets.
Keywords: CNS-penetrance, small molecules, PROTAC, molecular glue, allosteric, allosteric modulators, in silico drug design, neurodegenerative, cancer, dementia, Alzheimer's, Parkinsons
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.