Defactinib hydrochloride

SKU: orb1707391

Description

Defactinib hydrochloride is a potent and selective FAK inhibitor that suppresses autophosphorylation at Tyr397 in a time- and dose-dependent fashion. It is a valuable research tool for studying FAK's role in cancer cell migration, proliferation, and survival in both cellular and animal models of tumor progression.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 1073160-26-5
• MW: 546.95
• Purity: 98.78%
• Formula: C₂₀H₂₂ClF₃N₈O₃S
• SMILES: Cl.CNC(=O)c1ccc(Nc2ncc(c(NCc3nccnc3N(C)S(C)(=O)=O)n2)C(F)(F)F)cc1
• Target: FAK
• Solubility: DMSO:22.5 mg/mL (41.14 mM);H2O:0.1 mg/mL (0.18 mM);10% DMSO+40% PEG300+5% Tween-80+45% Saline:0.5 mg/mL (0.91 mM)

Bioactivity

• In Vivo:
  In the HeyA8 model, PTX monotherapy achieved an 87.4% decrease in tumor weight, while combination therapy yielded a superior 97.9% reduction (P=0.05 compared with PTX). Defactinib treatment at 25 mg/kg, administered orally twice daily, significantly decreased pFAK (Tyr397) levels, with effects reversing within 24 hours, establishing this dose for further experiments. For these, female nude mice with HeyA8 tumors in the peritoneal cavity were divided into four groups (n=10 each): 1) control group receiving vehicle and phosphate-buffered saline, 2) Defactinib (25 mg/kg orally, twice daily), 3) PTX weekly, and 4) both Defactinib and PTX. The SKOV3ip1 model demonstrated a 92.7% tumor weight reduction with the combination therapy compared to PTX alone (P<0.001).
• In Vitro:
  Defactinib suppresses pFAK (protein Focal Adhesion Kinase) expression within three hours, exhibiting a dose-dependent inhibition, particularly at the Tyr397 phosphorylation site, and showing a reduction in expression levels by 48 hours. It effectively diminishes FAK phosphorylation over time and in correlation with the administered dose. Additionally, Reverse Phase Protein Array (RPPA) analysis reveals that Defactinib lowers AKT and YB-1 levels in taxane-resistant cell lines. The inhibition of pFAK (Tyr397) by Defactinib is confirmed to be statistically significant and dose-responsive across various cell lines, as documented in source .

Storage & Handling

• Storage: keep away from direct sunlight | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Defactinib Hydrochloride, FAK, VS 6063 Hydrochloride, VS6063 Hydrochloride, VS-6063 hydrochloride, VS-6063 Hydrochloride, PF 04554878 hydrochloride, PF 04554878 Hydrochloride, PF04554878 Hydrochloride, PF-04554878 Hydrochloride

Compound Identifiers

PubChem CID

25117347