| CAS NO: | 1073154-85-4 |
| 规格: | ≥98% |
| 包装 | 价格(元) |
| 2mg | 询价 |
| 5mg | 询价 |
| 10mg | 询价 |
| 25mg | 询价 |
| 50mg | 询价 |
| 100mg | 询价 |
| 250mg | 询价 |
| 500mg | 询价 |
| 1g | 询价 |
| Molecular Weight (MW) | 510.49 |
|---|---|
| Formula | C20H21F3N8O3S |
| CAS No. | 1073154-85-4 |
| Storage | -20℃ for 3 years in powder form |
| -80℃ for 2 years in solvent | |
| Solubility (In vitro) | DMSO: 5 mg/mL (9.8 mM) |
| Water: <1 mg/mL | |
| Ethanol: <1 mg/mL | |
| Solubility (In vivo) | 5% DMSO+50% PEG 300+5% Tween 80+ddH2O: 5mg/mL |
| Synonyms | VS-6063; PF-04554878; VS6063; VS 6063; PF04554878; PF 04554878; PF4554878; Chemical Name: N-methyl-4-((4-(((3-(N-methylmethylsulfonamido)pyrazin-2-yl)methyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzamide SMILES Code: 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 |
| In Vitro | In vitro activity: In taxane-sensitive (SKOV3ip1) and taxane-resistant (SKOV3-TR) cell lines, Defactinib significantly inhibits pFAK (Tyr397) expression. The combination of Defactinib and paclitaxel synergistically decreases proliferation and increases apoptosis in SKOV3ip1, SKOV3-TR, HeyA8 and HeyA8-MDR cells. The combination of Defactinib and Y15 synergistically decreases viability, clonogenicity, and cell attachment in thyroid cancer cell lines. Kinase Assay: Defactinib inhibited FAK phosphorylation at the Tyr397 site in a time- and dose-dependent manner. The combination of Defactinib and paclitaxel markedly decreased proliferation and increased apoptosis, which resulted in 92.7% to 97.9% reductions in tumor weight. RPPA data showed that Defactinib reduced levels of AKT and YB-1 in taxane-resistant cell lines. FAK inhibition enhanced chemosensitivity in taxane-resistant cells by decreasing YB-1 phosphorylation and subsequently CD44 in an AKT-dependent manner. In human ovarian cancer samples, nuclear FAK expression was associated with increased nuclear YB-1 expression (χ2) = 37.7; P < .001). Coexpression of nuclear FAK and YB-1 was associated with statistically significantly worse median overall survival (24.9 vs 67.3 months; hazard ratio = 2.64; 95% confidence interval = 1.38 to 5.05; P = .006). Cell Assay: Ovarian cancer cells are treated with increasing concentrations of Defactinib for 96 hours and then subjected to the MTT assay. Results are confirmed with triplicate experiments. |
|---|---|
| In Vivo | In both PTX-sensitive and PTX-resistant models, Defactinib (50 mg/kg p.o.) enhances tumor growth inhibition by paclitaxel. |
| Animal model | Mice bearing SKOV3ip1, SKOV3-TR, HeyA8 or HeyA8-MDR tumors |
| Formulation & Dosage | Dissolved in PBS; 50 mg/kg; Administered through p.o. |
| References | J Natl Cancer Inst. 2013 Oct 2;105(19):1485-95; Oncotarget. 2014 Sep 15;5(17):7945-59. |
Y15 and PF-04554878 decreased cell viability in a dose-dependent manner in thyroid cancer cell lines. Oncotarget. 2014 Sep 15;5(17):7945-59. |
Y15 and PF-04554878 induced significant gene changes in medullary thyroid cancer TT cells. Oncotarget. 2014 Sep 15;5(17):7945-59. |
Y15 and PF-04554878 decreased clonogenicity in a dose-dependent manner in papillary thyroid cancer cell lines. Oncotarget. 2014 Sep 15;5(17):7945-59. |
In vitro biological effects of VS-6063 on taxane-sensitive and taxane-resistant cell lines. J Natl Cancer Inst. 2013 Oct 2;105(19):1485-95. |
In vivo effects of VS-6063 combined with paclitaxel (PTX). J Natl Cancer Inst. 2013 Oct 2;105(19):1485-95. |
VS-6063 restores YB-1–mediated paclitaxel (PTX) resistance. J Natl Cancer Inst. 2013 Oct 2;105(19):1485-95. |
VS-6063 downregulated YB-1 phosphorylation and nuclear translocation in taxane-resistant cells by an AKT-dependent pathway. J Natl Cancer Inst. 2013 Oct 2;105(19):1485-95. |
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