product name PND-1186 (VS-4718)
Description: PND-1186 (also known as SR-2156, or VS-4718) is a potent and reversible and selective FAK inhibitor with IC50 of 1.5 nM. PND-1186 has an IC50 of ~100 nM in breast carcinoma cells. Notably, 1.0 µM PND-1186 (>5-fold above IC50) had limited effects on cell proliferation. However, under non-adherent conditions as spheroids and as colonies in soft agar, 0.1 M PND-1186 blocked FAK and p130Cas tyrosine phosphorylation, promoted caspase-3 activation, and triggered cell apoptosis.
References: Cancer Biol Ther. 2010 May 15;9(10):764-77; Mol Cancer Ther. 2014 Aug;13(8):2050-61.
501.5
Formula
C25H26F3N5O3
CAS No.
1061353-68-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 24 mg/mL (47.8 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5mg/mL
Synonyms
SR-2156, VS-4718
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19420257
| In Vitro |
In vitro activity: In vitro, PND-1186 inhibits 4T1 breast carcinoma motility, promotes 4T1 apoptosis in suspended conditions, and decreases 4T1 soft agar colony number and size. In HEY and OVCAR8 cells, VS-4718 promotes G0-G1 cell-cycle arrest followed by cell death. Kinase Assay: GST-FAK in vitro kinase activity is measured and compared to His-tagged FAK 411–686 using the K-LISA screening kit and poly(Glu:Tyr) (4:1) copolymer as a substrate immobilized on microtiter plates. IC50 values are determined with various concentrations of test compounds in a buffer containing 50 µM ATP and 10 mM MnCl2, 50 mM HEPES (pH 7.5), 25 mM NaCl, 0.01% BSA, and 0.1 mM Na orthovanadate for 5 min at room temperature. Serial diluted compounds are tested in triplicate. Substrate phosphorylation is measured using horseradish peroxidase-conjugated anti-pTyr antibodies with spetrophotometric color quantitation. IC50 values are determined using the Hill-Slope Model. Kinase selectivity profiling is performed by using the KinaseProfiler service. Cell Assay: For soft agar assays, 48-well plates are coated with a 1:4 mix of 2% agar (EM Science) in 0.2 mL growth media (bottom layer). 5×104 cells are plated per well (in triplicate) in a mixture of 0.3% agar in 0.2 mL growth media (top layer). After agar solidification, 0.2 mL growth media is added containing DMSO or PND-1186 (final concentration for 0.6 mL). In separate experiments, PND-1186 is added after 4 days. After 10 days, colonies are imaged in phase contrast, enumerated by counting 9 fields (3 fields per well), and total area determined using Image J. For all analyses, experimental points are performed in triplicate and repeated at least two times. |
|---|---|
| In Vivo | In mice bearing 4T1 tumors, PND-1186 (100 mg/kg s.c.) inhibits 4T1 subcutaneous tumor growth by induction of apoptosis. In mice bearing ID8 tumors, PND-1186 (0.5 mg/mL for p.o.) also causes ovarian carcinoma tumor growth inhibition. |
| Animal model | Mice bearing ID8 tumors or 4T1 tumors |
| Formulation & Dosage | Dissolved in polyethylene glycol 400 (PEG400) in PBS (1:1) for s.c.; 5% sucrose for p.o.; 100 mg/kg every 12 hours for s.c.; 0.5 mg/mL for p.o.; Administered via s.c. or p.o. |
| References | Cancer Biol Ther. 2010 May 15;9(10):764-77; Mol Cancer Ther. 2014 Aug;13(8):2050-61. |
