Defactinib (VS-6063, PF-04554878)
Cat. No.: DC7695
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Chemical Structure
1073154-85-4
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Field of application
Defactinib is a potent, selective, and orally active FAK inhibitor with demonstrated tolerability and preliminary clinical activity working as a single agent as well as in combination with paclitaxel.
| Cas No.: |
1073154-85-4 |
| Chemical Name: |
Defactinib |
| Synonyms: |
Defactinib;4-(4-{[(3-methanesulfonyl-methyl-amino)-pyrazin-2-ylmethyl]-amino}-5-(trifluoromethyl)-pyrimidin-2-ylamino)-N-methyl-benzamide;N-methyl-4-[[4-[[3-[methyl(methylsulfonyl)amino]pyrazin-2-yl]methylamino]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide;VS6063;VS-6063;N-Methyl-4-[[4-[[[3-[methyl(methylsulfonyl)amino]-2-pyrazinyl]methyl]amino]-5-(trifluoromethyl)-2-pyrimidinyl]amino]benzamide;VS 6063 |
| SMILES: |
O=C(NC)C1=CC=C(NC2=NC=C(C(F)(F)F)C(NCC3=NC=CN=C3N(C)S(=O)(C)=O)=N2)C=C1 |
| Formula: |
C20H21F3N8O3S |
| M.Wt: |
510.492751836777 |
| Sotrage: |
2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO |
| Description: |
Defactinib is a novel FAK inhibitor with potential antiangiogenic and antineoplastic activities. |
| In Vivo: |
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 VS-6063 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) VS-6063 25 mg/kg orally twice daily; 3) PTX intraperitoneally weekly; and 4) both VS-6063 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)[1]. |
| In Vitro: |
VS-6063 inhibits FAK phosphorylation at the Tyr397 site in a time- and dose-dependent manner. The combination of VS-6063 and Paclitaxel markedly decreases proliferation and increases apoptosis, which results in 92.7% to 97.9% reductions in tumor weight. RPPA data shows that VS-6063 reduces levels of AKT and YB-1 in taxane-resistant cell lines. The expression of pFAK (Tyr397) is statistically significantly inhibited by VS-6063 in a dose-dependent manner in all cell lines. VS-6063 inhibits pFAK (Tyr397) expression within 3 hours, with a gradual return of expression by 48 hours[1]. |
MSDS
COA
| LOT NO. |
DOWNLOAD |
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| 2018-0101 |
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| 2018-0101 |
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