Voruciclib hydrochloride 是一种具有口服活性和选择性 CDK 抑制剂，Ki 为 0.626 nM-9.1 nM。Voruciclib hydrochloride 可以有效阻断 MCL-1 的转录调节子 CDK9。Voruciclib hydrochloride 抑制多种弥漫性大 B 细胞淋巴瘤 (DLBCL) 模型中 MCL-1 的表达。
货号:ajcx39332
CAS:1000023-05-1
分子式:C22H20Cl2F3NO5
分子量：506.3
溶解度:DMSO : ≥ 250 mg/mL (493.78 mM)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

Voruciclib hydrochloride is an orally active and selective CDK inhibitor with Ki values of 0.626 nM-9.1 nM. Voruciclib hydrochloride potently blocks CDK9, the transcriptional regulator of MCL-1. Voruciclib hydrochloride represses expression of MCL-1 in multiple models of diffuse large B-cell lymphoma (DLBCL)[1].

Voruciclib hydrochloride (0.5-5 µM; 6 hours) shows targeted downregulation of MCL-1 in both ABC and GCB subtypes[1].Ki values for each target such as CDK9/cyc T2, CDK9/cyc T1, CDK6/cyc D1, CDK4/cyc D1, CDK1/cyc B, and CDK1/cyc A for Voruciclib hydrochloride are 0.626 nM, 1.68 nM, 2.92 nM, 3.96 nM, 5.4 nM, 9.1 nM, respectively[1].

Combination of Voruciclib hydrochloride (200 mpk; Oral gavage) and Venetoclax (10 mpk, 1 mpk, 50 mpk, 25 mpk in U2932, RIVA, SU-DHL-4 and NU-DHL-1, respectively) leads to enhance tumor growth inhibition compared to either drug alone in U2932, RIVA, SU-DHL-4 (six days per week for 4 weeks), and NU-DHL-1 models (five days per week for 3 weeks) of DLBCL[1].

[1]. Dey J, et al. Voruciclib, a clinical stage oral CDK9 inhibitor, represses MCL-1 and sensitizes high-risk Diffuse Large B-cell Lymphoma to BCL2 inhibition. Sci Rep. 2017 Dec 21;7(1):18007.

Protocol:

CDK9/CycT1 1.68nM(Ki)

CDK9/cycT2 0.626nM(Ki)

CDK6/cycD1 2.92nM(Ki)

CDK4/CycD1 3.96nM(Ki)

CDK1/cycB 5.4nM(Ki)

CDK1/cycA 9.1nM(Ki)