Sharma Vikas, Gupta Mohit
School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India.
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, Oregon, USA.
Chem Biol Drug Des. 2022 Dec;100(6):968-980. doi: 10.1111/cbdd.14024. Epub 2022 Feb 14.
Protein kinases are key regulators of cellular signaling and play a critical role in oncogenesis. Inhibitors of protein kinases are pursued by both industry and academia as a promising target for cancer therapy. Within the protein kinases, the ATP site has produced more than 40 FDA-approved drugs. The ATP site is broadly composed of a hinge region, gatekeeper residues, DFG-loop, ribose pocket, and other hydrophobic regions. The hinge region in the ATP site can be used for designing potent inhibitors. In this review, we discuss some representative studies that will highlight the interactions of heterocyclic compounds with hinge regions of different kinases like BRAF kinase, EGRF kinase, MAP kinase, and Mps1 kinase.
蛋白激酶是细胞信号传导的关键调节因子，在肿瘤发生中起关键作用。蛋白激酶抑制剂作为一种有前景的癌症治疗靶点，受到了业界和学术界的关注。在蛋白激酶中，ATP结合位点已产生了40多种获美国食品药品监督管理局批准的药物。ATP结合位点主要由一个铰链区、守门残基、DFG环、核糖口袋和其他疏水区域组成。ATP结合位点中的铰链区可用于设计强效抑制剂。在这篇综述中，我们讨论了一些具有代表性的研究，这些研究将突出杂环化合物与不同激酶（如BRAF激酶、EGRF激酶、MAP激酶和Mps1激酶）的铰链区之间的相互作用。
