Defactinib-VS-6063-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEDefactinibCat. No.: HY-12289CAS No.: 1073154-85-4Synonyms: VS-6063; PF-04554878分式: CHFNOS分量: 510.49作靶点: FAK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 : 39

2、 mg/mL (76.40 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (4.07 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.08 mg/mL (4.07 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Defactinib (VS-6063; PF-04554878)种新型 FAK

3、抑制剂，抑制 FAK 在 Tyr397 位点磷酸化，这种作具有时间和剂量依赖性。IC50 & Target FAK 1体外研究 Defactinib (VS-6063) inhibits FAK phosphorylation at the Tyr397 site in a time- and dose-dependent manner.RPPA data shows that Defactinib reduces levels of AKT and YB-1 in taxane-resistant cell lines. Theexpression of pFAK (Tyr397) is s

4、tatistically significantly inhibited by Defactinib in a dose-dependent mannerin all cell lines. Defactinib inhibits pFAK (Tyr397) expression within 3 hours, with a gradual return ofexpression by 48 hours 1.体内研究 Defactinib (VS-6063) doses of 25 mg/kg twice a day or greater statistically significantly

5、 inhibits pFAK(Tyr397) at 3 hours, with return of expression noted by 24 hours. Therefore, administration of Defactinib at 25mg/kg twice a day is selected as the dosing schedule for subsequent therapy experiments. For therapyexperiments, female nude mice bearing HeyA8 tumors in the peritoneal cavity

6、 are randomly divided into 4groups (n=10 per group): 1) vehicle orally twice daily and phosphate-buffered saline intraperitoneally weekly(control); 2) Defactinib 25 mg/kg orally twice daily; 3) PTX intraperitoneally weekly; and 4) both VDefactinib25 mg/kg orally twice daily and PTX intraperitoneally

7、 weekly. There is an 87.4% reduction in tumor weight byPTX monotherapy in the HeyA8 model, and combination therapy resulted in the greatest tumor weightreduction, with a 97.9% reduction (P=0.05 compared with PTX). In the SKOV3ip1 model, a 92.7% tumorweight reduction is observed in the combination gr

8、oup compared with PTX (P 1.PROTOCOLAnimal Mice 1Administration 1 To determine the antitumor effects of Defactinib, SKOV3ip1, SKOV3-TR, HeyA8, and HeyA8-MDR cells areinjected intraperitoneally. One week after tumor cell injection, mice are randomly assigned to 4 groups of 10mice (control, PTX alone,

9、Defactinib alone, and PTX with Defactinib); treatment is initiated at 3-4 weeksfollowing injection. PTX at 2 mg/kg (SKOV3ip1 and SKOV3-TR) or 2.5 mg/kg (HeyA8 and HeyA8-MDR) isgiven intraperitoneally weekly; Defactinib at 25 mg/kg is given orally twice every day. Control mice receivedHBSS intraperit

10、oneally once a week and vehicle orally twice every day. Mice are monitored daily for adverseeffects of therapy and are killed on day 35 (SKOV3ip1 or SKOV3-TR), day 28 (HeyA8 or HeyA8-MDR), orwhen any of the mice seemed moribund. Total body weight, tumor incidence and mass, and the number oftumor nod

11、ules are recorded. Tumors are either fixed in formalin or embedded in paraffin or snap frozen inoptimal cutting temperature (OCT) compound in liquid nitrogen.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.MedChe

12、mE户使本产品发表的科研献 Science. 2017 Dec 1;358(6367). Nat Commun. 2019 Aug 16;10(1):3708. J Exp Clin Cancer Res. 2018 Jul 28;37(1):175. Sci Rep. 2019 May 20;9(1):7617. J Int Med Res. 2018 Apr;46(4):1311-1325.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Kang Y, et al. Role of focal adhesion kinase in regulating YB-1-mediated resistance in ovarian cancer. J Natl Cancer Inst. 2013 Oct2;105(19):1485-95.McePdfHeightCaut