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Virtual Screening and Molecular Docking: Discovering Novel c-KIT Inhibitors

Author(s):

Fernanda Mello Tavares, Angela Cristina Gomes, Edson Mareco Assunção, João Luiz Sobral de Medeiros, Marcus T. Scotti, Luciana Scotti* and Hamilton Mitsugu Ishiki  

Abstract:


Gastrointestinal stromal tumors (GISTs) are unusual cancers which begin in specialized cells in the gastrointestinal tract wall. Various strategies involving single-agents, combinations, and rapid complementary inhibitor cycling are now being used to control such tumors. Based on promising early clinical trial experience, certain novel KIT, and PDGFRA tyrosine kinase inhibitors have begun advanced clinical development. Resistance to tyrosine kinase inhibitors has brought immense difficulties, with patients now requiring additional therapeutic options. This review describes and discusses the last five years (2016-2020) in developing novel c-KIT kinase inhibitors using virtual screening and docking approaches. Computational techniques can be used to complement experimental studies to identify new candidate molecules for therapeutic use. Molecular modeling strategies allow analysis of the required characteristics that compounds must have to effectively bind c-KIT. Through such analyses, it is possible to both discover and design novel inhibitors against cancer-related proteins that play a critical role in tumor development (including of mutant strains). Docking showed potential in the detection of the key residues responsible for ligand recognition and are very helpful to understand the interactions in the active site that can be used to develop new compounds/classes of anticancer drugs and help millions of cancer patients.

Keywords:

novel c-Kit inhibitors, drug design, molecular docking

Affiliation:

Post graduate Program in Health Sciences, University of Western São Paulo (UNOESTE), Presidente Prudente, SP, Post graduate Program in Environmental and Regional Development Studies, University of Western São Paulo (UNOESTE) Presidente Prudente, SP, Post graduate Program in Environmental and Regional Development Studies, University of Western São Paulo (UNOESTE) Presidente Prudente, SP, University of Marília, SP, Cheminformatics Laboratory-Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba-Campus I 58051-970, João Pessoa, PB, Cheminformatics Laboratory-Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba-Campus I 58051-970, João Pessoa, PB, Post graduate Program in Health Sciences, University of Western São Paulo (UNOESTE), Presidente Prudente, SP



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