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Signature-based approaches for informed drug repurposing: targeting CNS disorders


CNS disorders, and in particular psychiatric illnesses, lack definitive disease-altering therapeutics. The limited understanding of the mechanisms driving these illnesses with the slow pace and high cost of drug development exacerbates this issue. For these reasons, drug repurposing – both a less expensive and time-efficient practice compared to de novo drug development – has been a promising strategy to overcome the paucity of treatments available for these debilitating disorders. While empirical drug-repurposing has been a routine practice in clinical psychiatry, innovative, informed, and cost-effective repurposing efforts using big data (“omics”) have been designed to characterize drugs by structural and transcriptomic signatures. These strategies, in conjunction with ontological integration, provide an important opportunity to address knowledge-based challenges associated with drug development for CNS disorders. In this review, we discuss various signature-based in silico approaches to drug repurposing, its integration with multiple omics platforms, and how this data can be used for clinically relevant, evidence-based drug repurposing. These tools provide an exciting translational avenue to merge omics-based drug discovery platforms with patient-specific disease signatures, ultimately facilitating the identification of new therapies for numerous psychiatric disorders.

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Fig. 1: Chronology of drug repurposing approaches.


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RS and REM outlined and wrote the manuscript. NDH and RSA participated in writing the GWAS section. KA participated in writing the signature-based repurposing and adverse drug reaction sections. ARH participated in writing the drug permeability and drug patent-related sections. JR participated in writing the precision medicine section. HME participated in writing the text-mining section. ASI, SAM, and JC participated in writing the drug classification section. JM participated in writing the structure-based repurposing section.

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Correspondence to Rammohan Shukla.

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Shukla, R., Henkel, N.D., Alganem, K. et al. Signature-based approaches for informed drug repurposing: targeting CNS disorders. Neuropsychopharmacol. 46, 116–130 (2021).

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