In Silico Chemogenomics Drug Repositioning Strategies for Neglected Tropical Diseases

Carolina    Horta    Andrade; Bruno    Junior    Neves; Cleber     Camilo    Melo-Filho; Juliana        Rodrigues; Diego    Cabral    Silva; Rodolpho    Campos    Braga; Pedro    Vitor Lemos    Cravo
doi:10.2174/0929867325666180309114824
Abstract

Only ~1% of all drug candidates against Neglected Tropical Diseases (NTDs) have reached clinical trials in the last decades, underscoring the need for new, safe and effective treatments. In such context, drug repositioning, which allows finding novel indications for approved drugs whose pharmacokinetic and safety profiles are already known, emerging as a promising strategy for tackling NTDs. Chemogenomics is a direct descendent of the typical drug discovery process that involves the systematic screening of chemical compounds against drug targets in high-throughput screening (HTS) efforts, for the identification of lead compounds. However, different to the one-drug-one-target paradigm, chemogenomics attempts to identify all potential ligands for all possible targets and diseases. In this review, we summarize current methodological development efforts in drug repositioning that use state-of-the-art computational ligand- and structure-based chemogenomics approaches. Furthermore, we highlighted the recent progress in computational drug repositioning for some NTDs, based on curation and modeling of genomic, biological, and chemical data. Additionally, we also present in-house and other successful examples and suggest possible solutions to existing pitfalls.
Keywords: Neglected tropical diseases, drug repositioning, chemogenomics, similarity search, machine learning, pharmacophores, protein alignment, docking.
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DOI https://dx.doi.org/10.2174/0929867325666180309114824	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
Current Medicinal Chemistry

In Silico Chemogenomics Drug Repositioning Strategies for Neglected Tropical Diseases

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