BMS-986195 - Btk 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBMS-986195Cat. No.: HY-112161CAS No.: 1912445-55-6分式: CHFNO分量: 370.42作靶点: Btk作通路: Protein Tyrosine Kinase/RTK储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 100 mg/mL (269.96 mM)* means sol

2、uble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.6996 mL 13.4982 mL 26.9964 mL5 mM 0.5399 mL 2.6996 mL 5.3993 mL10 mM 0.2700 mL 1.3498 mL 2.6996 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，

3、当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.75 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.75 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/2 Master of S

4、mall Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (6.75 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 BMS-986195个有效的、布鲁顿酪氨酸激酶 (BTK) 的不可逆共价抑制剂，其 IC50 值 1 nM。IC50 & Target IC50: 1.体外研究 BMS-986195 is a potent and highly selective inhibitor of BTK, which acts by covalently modifying an active-site cys

5、teine residue. BMS-986195 is more than 5000-fold selective for BTK over all kinases outside of theTec family, and selectivity ranges from 9- to 1010-fold within the Tec family. BMS-986195 inactivates BTK inhuman whole blood with a rapid rate of inactivation (3.510-4nM-1min-1) and potently inhibits a

6、ntigen-dependent interleukin-6 production, CD86 expression and proliferation in B cells (IC50 1.体内研究 In mice, BMS-986195 demonstrates robust efficacy in murine models of RA including CIA and CAIA,protecting against clinically evident disease, histologic joint damage and bone mineral density loss. In

7、 bothmice and monkeys, maximal efficacy is observed at doses 0.5 mg/kg PO QD, which achieves 95%inactivation of BTK in vivo. At similar doses, BMS-986195 is also highly protective against nephritis in theNZB/W mouse model of lupus. To investigate the dynamics of BTK inactivation and resynthesis of B

8、TK,cynomolgus monkeys are given single or multiple doses of BMS-986195. 100% peak inactivation of BTK isobtained with a single administration of BMS-986195 at 0.5 mg/kg PO 1.REFERENCES1. JR Burke, et al. BMS-986195 Is a Highly Selective and Rapidly Acting Covalent Inhibitor of Brutons Tyrosine Kinase with RobustEfficacy at Low Doses in Preclinical Models of RA and Lupus Nephritis. 2017 ACR/ARHP Annual Meeting, September 18, 2017.McePdfHeightCaution: Product has not been fully validated for medical appli