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BML-277

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Chemical Structure| 516480-79-8 同义名 : Chk2 Inhibitor II;C 3742;Checkpoint Kinase 2 Inhibitor II
CAS号 : 516480-79-8
货号 : A144417
分子式 : C20H14ClN3O2
纯度 : 99%+
分子量 : 363.797
MDL号 : MFCD08276917
存储条件：

粉末 Inert atmosphere,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 20 mg/mL(54.98 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • Chk2

    Chk2, IC50:15 nM
描述 Chk2 kinase is a key mediator of the DNA damage checkpoint. BML-277 is a Chk2 inhibitor with an IC50 value of 15nM. It rescued CD4+ and CD8+ cells from radiation-induced apoptosis in a dose-dependent manner with an EC50 of 3-7.6µM[2]. BML-277 at 1-10µM inhibited CHK2 phosphorylation at Thr68 at different time courses (30min, 1h, 2h, and 4h) in both Farage and SUDHL6 cells. Treatment of SUDHL4, SUDHL6, and Farage cells with 5μM BML-277 led to apoptosis of less than 30% cells. BML-277 at 1 and 5μM significantly diminished the physical interaction between ERK and CHK2 in Farage and SUDHL6 cells at 4h post-exposure. In SUDHL6, Farage, and OCI-LY3 cells, BML-277 at 1-10µM reduced CHK2 phosphorylation at Thr68 but increased ERK phosphorylation compared to the control cells. Intraperitoneal administration of BML-277 (1mg/kg) every other day for 20 days modestly inhibited tumor growth in mice bearing subcutaneous tumors of SUDHL6 cells compared to the vehicle-treated group. The combination treatment of BML-277 (1mg/kg) and ERK inhibitor (5mg/kg) for 20 days resulted in a significant reduction in Ki67 expression and tumor suppression in mice inoculated with SUDHL6 cells[3].
作用机制 BML-277 inhibits Chk2 in an ATP-competitive manner. The hydrogen bonding interactions are predicted to occur between the 5-amide group of the benzimidazole moiety and the backbone amide nitrogen and carbonyl group of MET 90[2].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.75mL

0.55mL

0.27mL

13.74mL

2.75mL

1.37mL

27.49mL

5.50mL

2.75mL
参考文献

[1]Arienti KL, Brunmark A, et al. Checkpoint kinase inhibitors: SAR and radioprotective properties of a series of 2-arylbenzimidazoles. J Med Chem. 2005 Mar 24;48(6):1873-85.

[2]Arienti KL, Brunmark A, Axe FU, et al. Checkpoint kinase inhibitors: SAR and radioprotective properties of a series of 2-arylbenzimidazoles. J Med Chem. 2005;48(6):1873-1885. doi:10.1021/jm0495935

[3]Dai B, Zhao XF, Mazan-Mamczarz K, et al. Functional and molecular interactions between ERK and CHK2 in diffuse large B-cell lymphoma. Nat Commun. 2011;2:402. Published 2011 Jul 19. doi:10.1038/ncomms1404