PF-07104091 is a CDK2/cyclin E1 inhibitor, a selective ATP-site inhibitor targeting the cyclin-bound activated state of the kinase [1].
PF-07104091 is a CDK2/cyclin E1 inhibitor, a selective ATP-site inhibitor targeting the cyclin-bound activated state of the kinase [1]. PF-07104091(Example 13) inhibited CDK2/cyclin E1, GSK3β, CDK1/cyclin A2, CDK4/cyclin D1, CDK6/cyclin D3 and CDK9, with Kis of 1.16, 537.81, 110, 238, 465 and 117 nM, respectively. PF-07104091 has anti-tumor activity for cyclin E1-amplified cancers. [1].
PF-07104091 inhibited T47D and KPL1 cells with IC50s of 0.785 and 0.603 μM, respectively [2].
The combination of abemaciclib and PF-07104091decreased T47D and KPL1 cells survival compared to either single agent [2].
参考文献:
[1]. Behenna, D. C.; Freeman-Cook, K. D.; Hoffman, R. L.; Nagata, A.; Ninkovic, S.; Sutton, S. C. Preparation of aminopyrazolylcyclopentyl carbamate derivatives for use as CDK2 inhibitors. WO 2020157652, 2020.
[2]. Gharbi S I, Pelletier L A, Espada A, et al. Crystal structure of active CDK4-cyclin D and mechanistic basis for abemaciclib efficacy[J]. npj Breast Cancer, 2022, 8(1): 126.
PF-07104091 是一种 CDK2/cyclin E1 抑制剂，一种靶向激酶 [1] 的细胞周期蛋白结合激活状态的选择性 ATP 位点抑制剂。 PF-07104091（实施例 13）抑制 CDK2/细胞周期蛋白 E1、GSK3β；CDK1/细胞周期蛋白 A2、CDK4/细胞周期蛋白 D1、CDK6/细胞周期蛋白 D3 和 CDK9，Kis 分别为 1.16、537.81、110、238、465 和 117 nM . PF-07104091 对细胞周期蛋白 E1 扩增的癌症具有抗肿瘤活性。 [1].
PF-07104091 抑制 T47D 和 KPL1 细胞，IC50 分别为 0.785 和 0.603 μM，[2]。
与任一单一药物相比，abemaciclib 和 PF-07104091 的组合降低了 T47D 和 KPL1 细胞的存活率[2]。
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Preparation Method |
1000 cell/well were seeded in 384-well plate in 20 μL of RPMI 1640, or DMEM, respectively in 10% FBS at 37 °C, 5%CO2. Assay-ready plates containing 1:3 serial dilutions of compounds in 100% DMSO were prepared using acoustic dispensing technology (ECHO), final starting concentration was 20 μM. Compound-treated plates were incubated for 4 days (2 doubling times) and cell proliferation estimated using PI staining. |
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Reaction Conditions |
0-20μM for 4 days |
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Applications |
PF-07104091 inhibited T47D and KPL1 cells with IC50s of 0.785 and 0.603 μM, respectively. |
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参考文献: [1]: Gharbi S I, Pelletier L A, Espada A, et al. Crystal structure of active CDK4-cyclin D and mechanistic basis for abemaciclib efficacy[J]. npj Breast Cancer, 2022, 8(1): 126. | |
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