BS-181 hydrochloride (BS-181 HCl) is a highly selective CDK7 inhibitor with IC50 of 21 nM. It is more than 40-fold selective for CDK7 than CDK1, 2, 4, 5, 6, or 9.

CDK7:21 nM

BS-181是一种小分子抑制剂，针对无细胞环境中的CDK7展现出较roscovitine更高的潜在活性，其IC 50为510 nM。在众多不同类别的CDKs和其他69种激酶中，BS-181对CDK7表现出高度的选择性抑制作用，对CDK2的抑制浓度低于1 μM，相较CDK7的抑制能力弱35倍（IC50为880 nM），对CDK1、CDK4、CDK5、CDK6和CDK9的抑制作用较弱，IC50值高于3.0 μM，仅在高浓度（>10 μM）下对其他类别的几种激酶显示出抑制作用。BS-181能促进细胞周期阻滞并抑制包括乳腺、肺、前列腺和结肠癌在内的多种肿瘤类型癌细胞的生长，IC50值范围为11.5-37 μM。在MCF-7细胞中，BS-181抑制了CDK7底物RNA聚合酶II COOH-末端域（CTD）的磷酸化，促进细胞周期阻滞和凋亡以抑制癌细胞系的生长。[1]

BS-181 在体内表现出稳定性，小鼠经过每千克体重10 mg的腹腔注射(i.p.)后，血浆消除半衰期为405分钟。BS-181 能够剂量依赖性地抑制裸鼠模型中MCF-7异种移植瘤的增长，在连续治疗2周后，每日10 mg/kg和20 mg/kg的剂量分别实现了25%和50%的肿瘤生长抑制，且未观察到明显的毒性。[1]

In vitro kinase inhibition.: Inhibition of CDK7 activity is measured by incubation of increasing amounts of BS-181 with purified recombinant CDK7/CycH/MAT1 complex, followed by measurement of free ATP remaining in the reaction using a luciferase assay, luciferase activity therefore providing a measure of inhibition of CDK7 activity for the determination of IC50.

MCF-7 cells are exposed to BS-181 for 24 hours. For the determination of cell cycle and apoptosis, cells are stained with propidium iodide or labeled with Annexin V-FITC, then labeled cells are acquired within 1 hour, by using the RXP cytomics software on a Beckman Coulter Elite ESP, and the data are analyzed using Flow Jo v7.2.5. For the assessment of CDKs, cells are lysed and analyzed by western blotting.(Only for Reference)