BMS-911543 - JAK 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBMS-911543Cat. No.: HY-15270CAS No.: 1271022-90-2分式: CHNO分量: 432.52作靶点: JAK作通路: Epigenetics; JAK/STAT Signaling; Stem Cell/Wnt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 : 25 mg/mL (57.80

2、 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.78 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.78 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 BMS-911543种选择性的 JAK2 抑制剂，IC50 值为 1.1 nM

3、，对 JAK1，JAK3 和 TYK2 的选择性相对较弱，IC50 值分别为 75，360 和 66 nM。IC50 & Target JAK2 Tyk2 JAK1 JAK31.1 nM (IC50) 66 nM (IC50) 75 nM (IC50) 360 nM (IC50)体外研究 BMS-911543 is a selective JAK2 inhibitor, with IC50s of 1.1 nM, less selective at JAK1, JAK3 and TYK2(IC50, 75, 360, 66 nM, respectively). BMS-911543 displ

4、ays IC50 of 25 M for all targets except PDE4(IC50, 5.6 M). BMS-911543 exhibits potent antiproliferative effect on the SET-2 and BaF3-V617Fengineered cell lines (both dependent upon JAK2 pathway), with IC50s of 60 and 70 nM, respectively, andsuch an effect on SET-2 and BaF3-V617F cells is correlated

5、with similar activity on constitutively activepSTAT5 (IC50, 80 and 65 nM, respectively) 1. BMS-911543 (20 M) is cytotoxic to murine or humanpancreatic ductal adenocarcinoma (PDAC) cell lines. BMS-911543 (5 and 10 M) also blocks T regulatorycell differentiation in vitro 2.体内研究 BMS-911543 is well tole

6、rated up to 100 mg/kg in rats (mean AUC0-72 h, 11300 Mh) and dogs (AUC0-24 h,610 Mh). A 15 mg/kg/day dose (Day 14 AUC0-24 h, 3200 Mh) is well tolerated 1 in two-week repeatdose studies in rats. BMS-911543 (30 mg/kg, p.o.) suppresses the growth of tumor and prolongs the mediansurvival in KPC-Brca1 mi

7、ce. BMS-911543 also selectively reduces pSTAT5 expression in pancreatic tumorsand decreases levels of intratumoral FoxP3+ T regulatory cells in mice administered BMS-911543 2.PROTOCOLCell Assay 2 Human and murine pancreatic ductal adenocarcinoma (PDAC) tumor cells or PSC are cultured in 96 wellplate

8、s and the following day treated with BMS-911543 or DMSO vehicle control for 48 hours. After 48 hours,MTT reagent (ATCC) is added for 2 hours at 37C. Samples are analyzed on a plate reader testing forabsorbance at 450 nM 2.MCE has not independently confirmed the accuracy of these methods. They are fo

9、r reference only.Animal Mice 2Administration 2 Pancreatic tumors are confirmed in KPC-Brca1 mice by bioluminescent imaging (BLI) at 5-6 weeks of age.Briefly, mice are maintained on isofluorane anesthesia and imaged 10-15 minutes following intraperitonealinjection of Luciferin on a heated platform. A

10、nimals with a pancreatic mass of approximately 50-100 mm3 arerandomized, and treatment is initiated the day following imaging. Mice are then treated for 2 weeks by dailyoral gavage at a dose of 30 mg/kg BMS-911543. Following 2 weeks of treatment, animals are euthanized viaCO2 asphyxiation followed b

11、y cardiac puncture. Plasma, splenocytes and tumor tissue are collected forfurther analysis. Pathology is assessed by H&E to determine differentiation state of the tissue as PanIN,papillary carcincoma or PDAC. For long term in vivo experiments, 8 week old KPC-Brca1 mice withadvanced disease are conti

12、nuously treated by oral gavage at 30 mg/kg of BMS-911543 until mice meetspecified early removal criteria 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE户使本产品发表的科研献 Sci Transl Med. 2018 Jul 18;10(450).

13、pii: eaaq1093. IUBMB Life. 2018 Jan;70(1):81-91.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Wan H, et al. Discovery of a Highly Selective JAK2 Inhibitor, BMS-911543, for the Treatment of Myeloproliferative Neoplasms. ACS MedChem Lett. 2015 Jul 12;6(8):850-5.2. Mace TA, et al. Single agent BMS-911543 Jak2 inhibitor has distinct inhibitory effects on STAT5 signaling in genetically engineered micewith pancreatic cancer. Oncotarget. 2015 Dec 29;6(42):44509-2