Defactinib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Defactinib (VS-6063, PF-04554878) 是一种有效的、选择性的、口服活性的 FAK 抑制剂，在癌细胞系中以剂量依赖性方式选择性抑制 pFAK (Tyr397)。

Defactinib (VS-6063, PF-04554878) is a potent, selective and orally active FAK inhibitor, selectively inhibits pFAK (Tyr397) in a dose-dependent manner in cancer cell lines; shows no statistically significant changes in FAK phosphorylation at the other residues(Tyr 576/577, Tyr 925, or Tyr 861), also inhibits Pyk2 Tyr402 phosphorylation in HeyA8 cells; markedly decreases proliferation and increases apoptosis combined with paclitaxel, reduces levels of AKT and YB-1 in taxane-resistant cell lines; significantly reduces tumor growth, synergized with the mTOR inhibitor everolimus in xenograft models of pancreatic tumor.Lung Cancer Phase 2 Clinical(In Vitro):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. The expression of pFAK (Tyr397) is statistically significantly inhibited by Defactinib in a dose-dependent manner in all cell lines. Defactinib inhibits pFAK (Tyr397) expression within 3 hours, with a gradual return of expression by 48 hours. (In Vivo):Defactinib (VS-6063) doses of 25 mg/kg twice a day or greater statistically significantly inhibits pFAK (Tyr397) at 3 hours, with return of expression noted by 24 hours. Therefore, administration of Defactinib at 25 mg/kg twice a day is selected as the dosing schedule for subsequent therapy experiments. For therapy experiments, female nude mice bearing HeyA8 tumors in the peritoneal cavity are randomly divided into 4 groups (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 VDefactinib 25 mg/kg orally twice daily and PTX intraperitoneally weekly. There is an 87.4% reduction in tumor weight by PTX monotherapy in the HeyA8 model, and combination therapy resulted in the greatest tumor weight reduction, with a 97.9% reduction (P=0.05 compared with PTX). In the SKOV3ip1 model, a 92.7% tumor weight reduction is observed in the combination group compared with PTX (P<0.001).

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VS-6063 | VS6063 | PF04554878 | PF-04554878

Angiogenesis

FAK

FAK

Cancer

Lung Cancer

1073154-85-4

510.4927

C20H21F3N8O3S

>98% (HPLC)

DMSO: ≥ 39 mg/mL

CNC(=O)C1=CC=C(NC2=NC=C(C(NCC3=NC=CN=C3N(C)S(C)(=O)=O)=N2)C(F)(F)F)C=C1

Benzamide, N-methyl-4-[[4-[[[3-[methyl(methylsulfonyl)amino]-2-pyrazinyl]methyl]amino]-5-(trifluoromethyl)-2-pyrimidinyl]amino]-

(-20℃)

With Ice Pack

≥ 2 years