LY-2857785
中文名称 | LY-2857785 |
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中文同义词 | CDK9,CDK8和CDK7抑制剂(LY2857785);反式-N1-(4-(3-异丙基-2-甲基-2H-吲唑-5-基)嘧啶-2-基)-N4-(四氢-2H-吡喃-4-基)环己烷-1,4-二胺;化合物LY2857785 |
英文名称 | LY2857785 |
英文同义词 | LY2857785;LY2857785 (LY 2857785;1,4-Cyclohexanediamine, N1-[4-[2-methyl-3-(1-methylethyl)-2H-indazol-5-yl]-2-pyrimidinyl]-N4-(tetrahydro-2H-pyran-4-yl)-, trans-;trans-N1-(4-(3-Isopropyl-2-methyl-2H-indazol-5-yl)pyrimidin-2-yl)-N4-(tetrahydro-2H-pyran-4-yl)cyclohexane-1,4-diamine;Cyclin dependent kinase,LY 2857785,CDK,Apoptosis,LY2857785,Inhibitor,inhibit,LY-2857785 |
CAS号 | 1619903-54-6 |
分子式 | C26H36N6O |
分子量 | 448.6 |
EINECS号 | |
相关类别 | 细胞生物学试剂 |
Mol文件 | 1619903-54-6.mol |
结构式 |
LY-2857785 性质
沸点 | 671.0±65.0 °C(Predicted) |
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密度 | 1.29±0.1 g/cm3(Predicted) |
储存条件 | 2-8°C(protect from light) |
溶解度 | 不溶于水;温和加热时,乙醇溶液中≥13.87 mg/mL; DMSO 中≥2.63 mg/mL,温和加热和超声波 |
形态 | 粉末 |
酸度系数(pKa) | 10.05±0.40(Predicted) |
颜色 | 白色至米白色 |
CDK9 0.011 μM (IC 50 ) |
CDK8 0.016 μM (IC 50 ) |
CDK7 0.246 μM (IC 50 ) |
LY2857785 shows good selectivity against a panel of 114 protein kinases, with only 5 other protein kinases inhibited with potency (IC 50 ) less than 0.1 μM, and a total of 14 kinases less than 1 μM. At the cellular level, LY2857785 inhibits CTD P-Ser2 and CTD P-Ser5 in U2OS cells at IC 50 s 0.089 (n=13) and 0.042 (n=1) μM, respectively. However, LY2857785 only induces a moderate G 2 -M DNA content increase, from 35% to 55%, with EC 50 0.135 μM. LY2857785 shows potent compound exposure- and time-dependent cell proliferation inhibition in MV-4-11, RPMI8226, and L363 cells. When incubated between 4 to 24 hours, the cell growth inhibition potency reaches a maximal effect at 8 hours with IC 50 s 0.04, 0.2, and 0.5 μM for MV-4-11, RPMI8226, and L363 cells, respectively. LY2857785-induced cancer cell apoptosis is also time dependent, reaching maximal potency at 8 hours with IC 50 0.5 μM in L363 cells.
In HCT116 xenograft tumor-bearing mice, LY2857785 demonstrates dose-dependent RNAP II CTD P-Ser2 inhibition potently with TED50 of 4.4 mg/kg and TEC50 of 0.36 μM. LY2857785 also shows significant duration of CTD P-Ser2 inhibition for 3 to 6 hours at TED70 (8 mg/kg) in HCT116 and MV-4-11 nude mice xenograft models. In the nude rat MV-4-11 xenograft model, LY2857785 similarly shows dose-dependent CTD P-Ser2 inhibition for 8 hours at TED70 (7 mg/kg) and TED90 (10 mg/kg). LY2857785 demonstrates the most dramatic tumor regression in the AML MV-4-11 xenograft tumor model either by i.v. bolus in mice or i.v. infusion in rats.
安全信息
更新日期 | 产品编号 | 产品名称 | CAS号 | 包装 | 价格 |
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2024/04/30 | HY-12293 | LY-2857785 LY2857785 | 1619903-54-6 | 2mg | 1100元 |
2024/04/30 | HY-12293 | LY-2857785 LY2857785 | 1619903-54-6 | 5mg | 1800元 |