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CAS No.: 2387704-62-1

SR-4835 Catalog No. CSN25349

SR-4835 is a potent, highly selective and ATP competitive dual inhibitor of CDK12/CDK13 with IC50 of 99 nM, Kd of 98 nM for CDK12 and Kd of 4.9 nM for CDK13. It acts in synergy with DNA-damaging chemotherapy and PARP inhibitors and provokes triple-negative breast cancer (TNBC) cell death.

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实验方案

技术信息

生物活性

描述The cyclin-dependent kinases (CDKs) 12 and 13 phosphorylate the C-terminal domain of RNA polymerase II, regulating transcription and co-transcriptional processes. SR-4835 is a highly selective dual inhibitor of CDK12 and CDK13 (CDK12: IC₅₀=99 nM, K_d=98 nM; CDK13: K_d=4.9 nM). R-4835 was highly selective toward CDK12 and CDK13 when tested in a panel of over 450 kinases at 10 μM. SR-4835 blocked Ser2 phosphorylation with a half maximal effective concentration (EC₅₀) of 100 nM, consistent with in-cell targeting of CDK12/13. In cell proliferation studies, TNBC cell lines were found to be highly sensitive to SR-4835, with median EC₅₀ values in the low nanomolar range. Similarly, SR-4835 completely blocked clonogenic growth and survival of MDA-MB-231 cells in long-term growth assays. SR-4835 treatment of MDA-MB-231 cells reduced the expression of a cast of DNA damage response (DDR) genes as early as 6 h after treatment. Furthermore, SR-4835 treatment (30 or 90 nM) provoked DNA damage and triggered apoptosis. In vivo, there was a marked decrease in tumor growth in mice treated with SR-4835 (orally 20 mg/kg 5 days on, 2 days off [5:2] schedule) compared with vehicle-treated mice^[1].
作用机制SR-4835 interacts via hydrogen bonding with the hinge region of the kinase (Tyr-815, Met-816, and Asp-819)^[1].
参考文献

[1] Quereda V, Bayle S, Vena F, et al. Therapeutic Targeting of CDK12/CDK13 in Triple-Negative Breast Cancer. Cancer Cell. 2019;36(5):545-558.e7

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 2.0026 mL
- 10.0129 mL
- 20.0258 mL
- 5 mM
- 0.4005 mL
- 2.0026 mL
- 4.0052 mL
- 10 mM
- 0.2003 mL
- 1.0013 mL
- 2.0026 mL

技术信息

CAS号

2387704-62-1

储存条件

粉末: Inert atmosphere,Room Temperature

液体: -20°C:3-6 月 -80°C:12月

分子式

C21H20Cl2N10O

运输

蓝冰

分子量

499.36

别名

溶解度

DMSO	100.0 mg/mL (200.3 mM)
Water	Insoluble
Ethanol	Insoluble

动物实验配方

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