Gastrointestinal stromal tumors (GISTs) are unusual cancers, which are developed 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 shown 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 the 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 mutant strains). Docking showed potential in the detection of the key residues responsible for ligand recognition and is 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.

中文翻译：

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虚拟筛选和分子对接：发现新型 c-KIT 抑制剂。

胃肠道间质瘤 (GIST) 是一种不常见的癌症，它在胃肠道壁的特殊细胞中发育。涉及单药、组合和快速互补抑制剂循环的各种策略现在正被用于控制此类肿瘤。基于有希望的早期临床试验经验，某些新型 KIT 和 PDGFRA 酪氨酸激酶抑制剂已显示出先进的临床开发。对酪氨酸激酶抑制剂的耐药性带来了巨大的困难，患者现在需要额外的治疗选择。本综述描述并讨论了过去五年（2016-2020）使用虚拟筛选和对接方法开发新型 c-KIT 激酶抑制剂的过程。计算技术可用于补充实验研究，以确定用于治疗用途的新候选分子。分子建模策略允许分析化合物必须具有的有效结合 c-KIT 所需的特征。通过此类分析，有可能发现和设计针对在肿瘤发展中起关键作用的癌症相关蛋白（包括突变株）的新型抑制剂。对接在检测负责配体识别的关键残基方面显示出潜力，并且对于了解可用于开发新化合物/抗癌药物的新化合物/类别并帮助数百万癌症患者的活性位点中的相互作用非常有帮助。有可能发现和设计针对在肿瘤发展中起关键作用的癌症相关蛋白（包括突变株）的新型抑制剂。对接在检测负责配体识别的关键残基方面显示出潜力，并且对于了解可用于开发新化合物/抗癌药物的新化合物/类别并帮助数百万癌症患者的活性位点中的相互作用非常有帮助。有可能发现和设计针对在肿瘤发展中起关键作用的癌症相关蛋白（包括突变株）的新型抑制剂。对接在检测负责配体识别的关键残基方面显示出潜力，并且对于了解可用于开发新化合物/抗癌药物的新化合物/类别并帮助数百万癌症患者的活性位点中的相互作用非常有帮助。