Description
| Description | Defactinib hydrochloride is a novel inhibitor of FAK. Which inhibits FAK phosphorylation at the Tyr397 site in a time- and dose-dependent manner. |
| In vitro | Defactinib inhibits pFAK expression within 3 hours, with a gradual return of expression by 48 hours. Defactinib inhibits FAK phosphorylation at the Tyr397 site in a time- and dose-dependent manner. RPPA data displays 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 [1]. |
| In vivo | 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). Defactinib (25 mg/kg; twice a day or greater statistically; 3 hours) treatment significantly inhibits pFAK (Tyr397), 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. In the SKOV3ip1 model, a 92.7% tumor weight reduction is observed in the combination group compared with PTX (P<0.001)[1]. |
| Synonyms | PF 04554878 hydrochloride, VS-6063 hydrochloride |
| Molecular Weight |
546.95 |
| Formula | C20H22ClF3N8O3S |
| CAS No. | 1073160-26-5 |
Storage
Powder: -20°C for 3 years
In solvent: -80°C for 2 years
Solubility Information
DMSO: 22.5mg/mL (41.1mM),
Need ultrasonic
H2O: 0.1 mg/mL (insoluble)
( < 1 mg/ml refers to the product slightly soluble or insoluble )
