Branebrutinib

产品说明书

Print
Chemical Structure| 1912445-55-6 同义名 : -
CAS号 : 1912445-55-6
货号 : A634234
分子式 : C20H23FN4O2
纯度 : 98%
分子量 : 370.421
MDL号 : MFCD31631584
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 145 mg/mL(391.45 mM)，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
描述 Bruton's tyrosine kinase (BTK), a non-receptor tyrosine kinase, is a member of the Tec family of kinases and is essential for B cell receptor (BCR) mediated signaling. BTK also plays a critical role in the downstream signaling pathways for the Fcγ receptor in monocytes, the Fcε receptor in granulocytes, and the RANK receptor in osteoclasts [1]. BMS-986195 is a highly potent, selective covalent, irreversible inhibitor of BTK with an IC50 value of 0.1 nM [1]. BMS-986195 was highly effective at inhibiting TNFα production with equivalent potency to those measured for the BCR-dependent end points in B cells. In human whole blood assays, it potently inhibited BCR-stimulated expression of CD69 on B cells with an IC50 of 11 nM [1]. When administered orally to BALB/c mice, BMS-986195 dose-dependently inactivated BTK in peripheral blood with a single dose of 0.5 mg/kg, providing 90% inactivation 4 h after dosing. In addition, BMS-986195 provided a dose-dependent protection against pitting, loss of bone mass, woven porous bone, and fusion of the small bones evident in the mice receiving only vehicle [1].
作用机制 The tetrahydrocarbazole NH and the carboxamide carbonyl of BMS-986195 are engaged in a hydrogen bonding interaction with Met477 in the hinge region of the active site of BTK .
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.70mL

0.54mL

0.27mL

13.50mL

2.70mL

1.35mL

27.00mL

5.40mL

2.70mL
参考文献

[1]Watterson SH, Liu Q, Beaudoin Bertrand M, Batt DG, Li L, Pattoli MA, Skala S, Cheng L, Obermeier MT, Moore R, Yang Z, Vickery R, Elzinga PA, Discenza L, D'Arienzo C, Gillooly KM, Taylor TL, Pulicicchio C, Zhang Y, Heimrich E, McIntyre KW, Ruan Q, Westhouse RA, Catlett IM, Zheng N, Chaudhry C, Dai J, Galella MA, Tebben AJ, Pokross M, Li J, Zhao R, Smith D, Rampulla R, Allentoff A, Wallace MA, Mathur A, Salter-Cid L, Macor JE, Carter PH, Fura A, Burke JR, Tino JA. Discovery of Branebrutinib (BMS-986195): A Strategy for Identifying a Highly Potent and Selective Covalent Inhibitor Providing Rapid in Vivo Inactivation of Bruton's Tyrosine Kinase (BTK). J Med Chem. 2019 Apr 11;62(7):3228-3250. doi: 10.1021/acs.jmedchem.9b00167. Epub 2019 Mar 29. PMID: 30893553.