Defactinib, also known as VS-6063 and PF04554878, is an orally bioavailable, small-molecule focal adhesion kinase (FAK) inhibitor with potential antiangiogenic and antineoplastic activities. Defactinib inhibits FAK, which may prevent the integrin-mediated activation of several downstream signal transduction pathways, including those involving RAS/MEK/ERK and PI3K/Akt, thus inhibiting tumor cell migration, proliferation, survival, and tumor angiogenesis.
Chemical Formula: C20H22ClF3N8O3S
Molecular Weight: 546.9542
Elemental Analysis: C, 43.92; H, 4.05; Cl, 6.48; F, 10.42; N, 20.49; O, 8.78; S, 5.86
Chemical Name: N-Methyl-4-((4-(((3-(methyl(methylsulfonyl)amino)pyrazin-2-yl)methyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzamide monohydrochloride
InChi Code: InChI=1S/C20H21F3N8O3S.ClH/c1-24-18(32)12-4-6-13(7-5-12)29-19-28-10-14(20(21,22)23)16(30-19)27-11-15-17(26-9-8-25-15)31(2)35(3,33)34;/h4-10H,11H2,1-3H3,(H,24,32)(H2,27,28,29,30);1H
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
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.
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).
Roy-Luzarraga M, Hodivala-Dilke K. Molecular Pathways: Endothelial Cell FAK-A Target for Cancer Treatment. Clin Cancer Res. 2016 Aug 1;22(15):3718-24. doi: 10.1158/1078-0432.CCR-14-2021. PubMed PMID: 27262114.
Shimizu T, Fukuoka K, Takeda M, Iwasa T, Yoshida T, Horobin J, Keegan M, Vaickus L, Chavan A, Padval M, Nakagawa K. A first-in-Asian phase 1 study to evaluate safety, pharmacokinetics and clinical activity of VS-6063, a focal adhesion kinase (FAK) inhibitor in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2016 May;77(5):997-1003. doi: 10.1007/s00280-016-3010-1. PubMed PMID: 27025608; PubMed Central PMCID: PMC4844649.
Jones SF, Siu LL, Bendell JC, Cleary JM, Razak AR, Infante JR, Pandya SS, Bedard PL, Pierce KJ, Houk B, Roberts WG, Shreeve SM, Shapiro GI. A phase I study of VS-6063, a second-generation focal adhesion kinase inhibitor, in patients with advanced solid tumors. Invest New Drugs. 2015 Oct;33(5):1100-7. doi: 10.1007/s10637-015-0282-y. PubMed PMID: 26334219.
François RA, Maeng K, Nawab A, Kaye FJ, Hochwald SN, Zajac-Kaye M. Targeting Focal Adhesion Kinase and Resistance to mTOR Inhibition in Pancreatic Neuroendocrine Tumors. J Natl Cancer Inst. 2015 May 12;107(8). pii: djv123. doi: 10.1093/jnci/djv123. PubMed PMID: 25971297; PubMed Central PMCID: PMC4554194.
Lee BY, Timpson P, Horvath LG, Daly RJ. FAK signaling in human cancer as a target for therapeutics. Pharmacol Ther. 2015 Feb;146:132-49. doi: 10.1016/j.pharmthera.2014.10.001. Review. PubMed PMID: 25316657.
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