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Defactinib
Defactinib is a selective, and orally active focal adhesion kinase (FAK) inhibitor [1].?
FAK is a nonreceptor tyrosine kinase involved in many oncogenic pathways. Increased expression of FAK has been observed in a number of tumor types, including breast, colon, and ovarian cancers. It has been reported that FAK inhibition can sensitize cancer cells to chemotherapy [1].?
In Taxane-sensitive (HeyA8) and Taxane-resistant (HeyA8-MDR) cell lines, Defactinib at 0 ~ 10 μM significantly inhibited pFAK (Tyr397) expression in a dose-dependent manner. In addition, simultaneous exposure to doses of Paclitaxel and Defactinib at ratios of 1:1000 for HeyA8 and 1:10 for HeyA8-MDR showed a synergistic inhibitory effect on cell growth [1].?
In mice bearing HeyA8 tumors, there was a 97.9% reduction in tumor weight by the combination therapy (Defactinib: 25 mg/kg orally twice daily, Paclitaxel: 2.5 mg/kg intraperitoneally weekly), compared with an 87.4% reduction in tumor weight by Paclitaxel monotherapy. In the SKOV3ip1 model, a 92.7% tumor weight reduction was observed in the combination group (Defactinib: 25 mg/kg orally twice daily, Paclitaxel: 2 mg/kg intraperitoneally weekly) [1].?
Reference:
[1]. Kang Y, Hu W, Ivan C, et al. Role of focal adhesion kinase in regulating YB-1-mediated paclitaxel resistance in ovarian cancer. Journal of the National Cancer Institute, 2013, 105(19): 1485-1495.
| Storage | Store at -20°C |
| M.Wt | 510.49 |
| Cas No. | 1073154-85-4 |
| Formula | C20H21F3N8O3S |
| Solubility | insoluble in EtOH; insoluble in H2O; ≥160.2 mg/mL in DMSO |
| Chemical Name | N-methyl-4-[[4-[[3-[methyl(methylsulfonyl)amino]pyrazin-2-yl]methylamino]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide |
| SDF | Download SDF |
| Canonical SMILES | CNC(=O)C1=CC=C(C=C1)NC2=NC=C(C(=N2)NCC3=NC=CN=C3N(C)S(=O)(=O)C)C(F)(F)F |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment:[1] | |
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Cell lines |
Taxane-sensitive (HeyA8) and taxane-resistant (HeyA8-MDR) human epithelial ovarian cancer cell lines |
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Reaction Conditions |
0 ~ 10 μM defactinib |
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Applications |
In HeyA8 and HeyA8-MDR cell lines, defactinib at 0 ~ 10 μM significantly inhibited pFAK (Tyr397) expression in a dose-dependent manner. In addition, simultaneous exposure to doses of paclitaxel and defactinib at ratios of 1:1000 for HeyA8 and 1:10 for HeyA8-MDR showed a synergistic inhibitory effect on cell growth. |
| Animal experiment:[1] | |
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Animal models |
Female athymic nude mice (aged 8 ~ 12 weeks) |
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Dosage form |
25 mg/kg Twice daily by oral route |
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Applications |
In mice bearing HeyA8 tumors, there was a 97.9% reduction in tumor weight by the combination therapy (defactinib: 25 mg/kg orally twice daily; paclitaxel: 2.5 mg/kg intraperitoneally weekly), compared with an 87.4% reduction in tumor weight by paclitaxel monotherapy. In the SKOV3ip1 model, a 92.7% tumor weight reduction was observed in the combination group (defactinib: 25 mg/kg orally twice daily; paclitaxel: 2 mg/kg intraperitoneally weekly). |
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Note |
The technical data provided above is for reference only. |
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References: 1. Kang Y, Hu W, Ivan C, et al. Role of focal adhesion kinase in regulating YB-1-mediated paclitaxel resistance in ovarian cancer. Journal of the National Cancer Institute, 2013, 105(19): 1485-1495. |
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Quality Control & MSDS
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Chemical structure
