Chemogenomics and bioinformatics approaches for prioritizing kinases as drug targets for neglected tropical diseases

Author(s)

Verde Bastos Borba, Joyce Villa ; Silva, Arthur Carvalho ; Nascimento Lima, Marilia Nunes ; Mendonca, Sabrina Silva ; Furnham, Nicholas ; Maranhao Costa, Fabio Trindade ; Andrade, Carolina Horta ; Donev, R

• Document type: Journal article
• Source: ADVANCES IN PROTEIN CHEMISTRY AND STRUCTURAL BIOLOGY, VOL 124: PROTEIN KINASES IN DRUG DISCOVERY; v. 124, p. 37-pg., 2021-01-01.

Abstract

Neglected tropical diseases (NTDs) are a group of twenty-one diseases classified by the World Health Organization that prevail in regions with tropical and subtropical climate and affect more than one billion people. There is an urgent need to develop new and safer drugs for these diseases. Protein kinases are a potential class of targets for developing new drugs against NTDs, since they play crucial role in many biological processes, such as signaling pathways, regulating cellular communication, division, metabolism and death. Bioinformatics is a field that aims to organize large amounts of biological data as well as develop and use tools for understanding and analyze them in order to produce meaningful information in a biological manner. In combination with chemogenomics, which analyzes chemical-biological interactions to screen ligands against selected targets families, these approaches can be used to stablish a rational strategy for prioritizing new drug targets for NTDs. Here, we describe how bioinformatics and chemogenomics tools can help to identify protein kinases and their potential inhibitors for the development of new drugs for NTDs. We present a review of bioinformatics tools and techniques that can be used to define an organisms kinome for drug prioritization, drug and target repurposing, multi-quinase inhibition approachs and selectivity profiling. We also present some successful examples of the application of such approaches in recent case studies. (AU)

• FAPESP's process: 17/18611-7 - Development of new tools for search and validation of molecular targets for therapy against Plasmodium vivax
• Grantee: Fabio Trindade Maranhão Costa
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/21854-4 - Kinase prioritization and discovery of compounds with anti-malarial activity against different stages of Plasmodium vivax using chemogenomics, bioinformatics, cheminformatics, and experimental evaluation tools
• Grantee: Joyce Villa Verde Bastos Borba
• Support Opportunities: Scholarships in Brazil - Post-Doctoral