olomoucine

Olomoucine 是 Cdk2/cyclin A、Cdc2/CyclinB、CDK2/CyclinE、CDK5/p35 和 ERK1/p44 MAP 激酶的 ATP 竞争性抑制剂，IC50 分别为 7、7、7、3 和 25 µM。 Olomoucine 调节细胞周期并表现出抗黑色素肿瘤活性。

Olomoucine II 是一种高效的细胞周期蛋白依赖性激酶抑制剂，对 CDK1、CDK2、CDK4、CDK7 和 CDK9 的 IC50 分别为 7.6、0.1、19.8、0.45 和 0.06 μM。Olomoucine II 对多种其他激酶具有较高选择性，同时对 ERK2 和 ABCB1 保持可检测的活性。Olomoucine II 可在不同 p53 状态的癌细胞系中抑制细胞增殖，并在 ABCB1 表达的 HCT-8 细胞中与 daunorubicin 产生协同作用。此外，Olomoucine II 还能抑制 HSV-1、HSV-2、痘苗病毒、腺病毒 4 型及人巨细胞病毒的复制，是一种重要的抗病毒和抗癌研究工具。

9-Isopropylolomoucine (N9-Isopropylolomoucine) 是一种细胞周期蛋白依赖性激酶抑制剂，是一种硫嘌呤。

Potent cdk1 inhibitor (IC50 = 25 nM). Reduces Akt phosphorylation and increases mitochondrial damage in leukemia cells in vitro in combination with LY 294002. Yu et al (2013) The lethal effects of pharmacological cyclin-dependent kinase inhibitors in human leukemia cells proceed through a phosphatidylinositol 3-kinase/Akt-dependent process. Cancer Res. 63 1822 PMID:12702569 |Furet et al (2000) Structure-based design of potent CDK1 inhibitors derived from olomoucine. J.Comput.Aided Mol.Des. 14 403 PMID:10896313

Ibulocydine is a potent CDK inhibitor. Ibulocydine has high activity against Cdk7/cyclin H/Mat1 and Cdk9/cyclin T. Ibulocydine inhibited the growth of HCC cells more effectively than other Cdk inhibitors, including olomoucine and roscovitine, whereas ibulocydine as well as the other Cdk inhibitors and BMK-Y101 minimally influenced the growth of normal hepatocyte cells. Ibulocydine induced apoptosis in HCC cells, most likely by inhibiting Cdk7 and Cdk9. In vitro treatment of HCC cells with ibulocydine rapidly blocked phosphorylation of the carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase II, a process mediated by Cdk7/9. Anti-apoptotic gene products such as Mcl-1, survivin, and X-linked IAP (XIAP) are crucial for the survival of many cell types, including HCC. Following the inhibition of RNA polymerase II phosphorylation, ibulocydine caused rapid down-regulation of Mcl-1, survivin, and XIAP, thus inducing apoptosis. Furthermore, ibulocydine effectively ind......