PND1186 是一种高特异性的FAK可逆抑制剂，IC50为 1.5 nM。它选择性促进肿瘤细胞凋亡。

PND-1186 (VS-4718) is a reversible and specific FAK inhibitor (IC50: 1.5 nM).

在负荷4T1肿瘤的小鼠体内,PND-1186（100 mg/kg,s.c.）可诱导细胞凋亡,对4T1皮下肿瘤生长产生抑制作用.在负荷ID8肿瘤的小鼠体内,PND-1186（0.5 mg/mL,p.o.）还会抑制卵巢癌肿瘤的生长.

在体外,PND-1186对4T1乳腺癌能动性有抑制作用,且可促进悬浮状态的4T1凋亡,并使4T1软琼脂集落数量和大小减少。在HEY 和 OVCAR8细胞中,PND-1186促使G0-G1细胞周期阻滞,从而使细胞死亡。

In vitro kinase activity: 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.

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. (Only for Reference)

1061353-68-1

C25H26F3N5O3

501.5

PND1186;PND 1186;VS-4718;SR-2516

DMSO:23 mg/mL (45.9 mM)
Ethanol:<1 mgml
H2O:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years