BS-194(BS-194) - 药物靶点：CDK1 x CDK2 x CDK5 x CDK7 x CDK9_在研适应症：肿瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名-

靶点

CDK1 x CDK2 x CDK5 x CDK7 x CDK9

作用机制

CDK1抑制剂(细胞周期蛋白依赖性激酶1抑制剂)、CDK2抑制剂(细胞周期蛋白依赖性激酶2抑制剂)、CDK5抑制剂(细胞周期蛋白依赖性激酶5抑制剂)

+ [2]

治疗领域

肿瘤

在研适应症

肿瘤

非在研适应症-

原研机构

Imperial College London

在研机构

Imperial College London

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

100 项与 BS-194 相关的临床结果

登录后查看更多信息

100 项与 BS-194 相关的转化医学

登录后查看更多信息

100 项与 BS-194 相关的专利（医药）

登录后查看更多信息

1

项与 BS-194 相关的文献（医药）

2012-10-01·Journal of Molecular Recognition4区 · 生物学

Exploring the selectivity of a ligand complex with CDK2/CDK1: a molecular dynamics simulation approach

4区 · 生物学

Article

作者: Reddy, Karnati Konda ; Singh, Poonam ; Selvaraj, Chandrabose ; Chellaperumal, Palanisamy ; Tripathi, Sunil Kumar ; Singh, Sanjeev Kumar

Cyclin‐dependent kinases (CDKs) are core components of the cell cycle machinery that govern the transition between phases during cell cycle progression. Abnormalities in CDKs activity and regulation are common features of cancer, making CDK family members attractive targets for the development of anticancer drugs. Their inhibitors have entered in clinical trials to treat cancer. Very recently, Heathcote et al. (J. Med. Chem. 2010, 53:8508–8522) have found a ligand BS194 that has a high affinity with CDK2 (IC50 = 3 nm) but shows low affinity with CDK1 (IC50 = 30 nm). To understand the selectivity, we used homology modeling, molecular docking, molecular dynamics, and free‐energy calculation to analyze the interactions. A rational three‐dimensional model of the CDK1/BS194 complex is built. We found that Leu83 is a key residue that recognizes BS194 more effectively with CDK2 with good binding free energies rather than CDK1. Energetic analysis reveals that van der Waals interaction and non‐polar contributions to solvent are favorable in the formation of complexes and amine group of the ligand, which plays a crucial role for binding selectivity between CDK2 and CDK1. Copyright © 2012 John Wiley & Sons, Ltd.

100 项与 BS-194 相关的药物交易

登录后查看更多信息