| Protocol | 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 | Dissolved in PBS |
|---|
| Dosages | 50 mg/kg; Administered through p.o. |
|---|
These protocols are for reference only. InvivoChem does not
independently validate these methods.
Preparing Stock Solutions
| Solvent volume to be added |
Mass (the weight of a compound) |
| Mother liquor concentration |
1mg | 5mg | 10mg | 20mg |
| 1mM | 1.9589 mL | 9.7945 mL | 19.5890 mL | 39.1780 mL |
|---|
| 5mM | 0.3918 mL | 1.9589 mL | 3.9178 mL | 7.8356 mL |
|---|
| 10mM | 0.1959 mL | 0.9795 mL | 1.9589 mL | 3.9178 mL |
|---|
| 20mM | 0.0979 mL | 0.4897 mL | 0.9795 mL | 1.9589 mL |
|---|
|
Quality Control Documentation
|
|
: 
