CDK9 inhibitor 2 是一种特殊的细胞周期蛋白依赖性激酶 9 (CDK9) 抑制剂，提取自专利 WO/2012131594A1，化合物 CDKI(8)，在 H929 多发性骨髓瘤 (MM) 细胞系中的 IC50 分别为 5 nM 和 7 nM（72 小时） ) 和 A2058 皮肤细胞系（72 小时）。
CDK9-IN-2 is a special cyclin-dependent kinase 9 (CDK9) inhibitor, extracted from patent WO/2012131594A1, compound CDKI(8), has an IC50 of 5 nM and 7 nM in H929 multiple myeloma(MM) cell line (72 hours) and A2058 skin cell line (72 hours), respectively.
CDK9-IN-2 (200 nM) reduces the expression of MEPCE indicating that MEPCE is a pharmacodynamic (PD) marker for any CDK9 inhibitor. The expression of MCL1 protein is reduced 2 hours after treatment and is further reduced after 16 hour exposure to CDK9-IN-2 (500 nM)[1].
参考文献:
[1]. Michel Faure, et al. Pharmacodynamic markers associated with cyclin-dependent kinase inhibitors. From PCT Int. Appl. (2012), WO 2012131594A1.
Cell experiment: | H929, A2058, A375, U87MG, and NCIH441 cell lines are treated with CDK9-IN-2 at 500 nM (high) or 200 nM (low) at different time points. Five cell lines are analyzed: NCI-H929, a multiple myeloma cell line; NCI-H441 , a lung papillary adenocarcinoma cell line; A375, a melanoma cell line; A2058, a melanoma cell line and U-87-MG, a glioblastoma cell line. Cell lines are grown in the medium recommended by ATCC and treated as follows: NCI-H929: 2 hours: DMSO, 200 nM CDK9-IN-2 or 500nM CDK9-IN-2. NCI-H441 and A375: 0 timepoint: Untreated, harvested when compound is added to the other plates. 2 hours: DMSO, 200 nM CDK9-IN-2 or 500 nM CDK9-IN-2 or 500 nM CKDI(7) (3 plates each, total 12 plates).8 hours: DMSO, 200 nM CDK9-IN-2 or 500 nM CDK9-IN-2 or 500 nM CKDI(7) (3 plates each, total 12 plates).16 hours: DMSO, 200 nM CDK9-IN-2 or 500 nM CDK9-IN-2 or 500 nM CKDI(7) (3 plates each, total 12 plates). A2058 and U-87-MG: 0 timepoint: Untreated, harvested when compound is added to the other plates (3 plates). 2 hours: DMSO, 500 nM CDK9-IN-2 (3 plates each, total 6 plates). 8 hours: DMSO, 500 nM CDK9-IN-2 (3 plates each, total 6 plates).16 hours: DMSO, 500 nM CDK9-IN-2 (3 plates each, total 6 plates). The IC50s arethe analysed[1]. |
参考文献: [1]. Michel Faure, et al. Pharmacodynamic markers associated with cyclin-dependent kinase inhibitors. From PCT Int. Appl. (2012), WO 2012131594A1. | |
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