Defactinib

SKU: orb1306800

Description

Defactinib (VS-6063) is a second-generation, ATP-competitive FAK inhibitor that blocks autophosphorylation at Tyr397. It demonstrates antitumor activity in research, showing efficacy in in vitro cell proliferation assays and in vivo models of cancer metastasis and tumor growth inhibition.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 1073154-85-4
• MW: 510.49
• Purity: 99.13%
• Formula: C₂₀H₂₁F₃N₈O₃S
• SMILES: CNC(=O)c1ccc(Nc2ncc(c(NCc3nccnc3N(C)S(C)(=O)=O)n2)C(F)(F)F)cc1
• Target: FAK
• Solubility: DMSO:50 mg/mL (97.95 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:5 mg/mL (9.79 mM)

Bioactivity

• Target IC50:
  TT cells:1.98 µM|B-CPAP cells:23.04 µM|A549 cells:4.09 μM|MDA-MB-231 cells:3.75 μM|HEK293 cells:4.07 μM|HCT116 cells:2.65 μM|MCF-10A cells:18.42 μM|L02 cells:4.66 μM|MCF-7 cells:5.81 μM|HUVECs:3.24 μM|TPC1 cells:> 50 µM|K1 cells:10.34 µM|HepG2 cells:3.69 μM|HCT15 cells:4.36 μM|BxPC-3 cells:3.25 μM
• In Vivo:
  METHODS: To assay antitumor activity in vivo, Defactinib (25 mg/kg orally twice daily) and PTX (2 mg/kg intraperitoneally once weekly) were administered to thymus-free nude mice bearing SKOV3ip1, SKOV3-TR, HeyA8 or HeyA8-MDR xenografts for 35 or 28 days. RESULTS: In the HeyA8 model, PTX monotherapy resulted in an 87.4% reduction in tumor weight, and combination therapy resulted in the greatest reduction in tumor weight, 97.9% compared with PTX. In the SKOV3ip1 model, tumor weight was reduced by 92.7% in the combination group compared to PTX.Treatment with PTX alone was ineffective in the HeyA8 MDR model and the SKOV3-TR model, but treatment with Defactinib resulted in a reduction in tumor weight of 42.6% and 67.1%, respectively, with the combination leading to an even greater reduction in tumor growth.
• In Vitro:
  METHODS: Thyroid cancer cell lines TT, K1, BCPAP and TPC1 were treated with Defactinib (1-50 µM) for 24 h and cell viability was measured by MTS assay. RESULTS: Defactinib reduced cell viability in a dose-dependent manner in TT, K1, BCPAP and TPC1 cell lines with IC50s of 1.98 µM, 10.34 µM, 23.04 µM and >50 µM, respectively. METHODS: Taxane-sensitive cell line HeyA8 and Taxane-resistant cell line HeyA8-MDR were treated with Defactinib (0.001-10 mM) for 1-48 h, and target protein expression levels were detected by Western Blot. RESULTS: Defactinib statistically significantly inhibited the expression of pFAK (Tyr397) in a dose-dependent manner. pFAK (Tyr397) expression was inhibited by Defactinib within 3 h and was gradually restored within 48 h. Defactinib was also shown to inhibit pFAK (Tyr397) expression in a dose-dependent manner.
• Cell Research:
  Ovarian cancer cells are treated with increasing concentrations of VS-6063 for 96 hours and then subjected to the MTT assay. Results are confirmed with triplicate experiments.(Only for Reference)

Storage & Handling

• Storage: store at low temperature | 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, inhibit, Focal adhesion kinase, FAK, Inhibitor, PF 04554878, PF04554878, PF-04554878, PTK2 protein tyrosine kinase 2, PTK2, VS 6063, VS6063, VS-6063

Compound Identifiers

PubChem CID

25117126