Chemren Bio-Engineering Co., Ltd.

PND-1186 is a potent FAK inhibitor with IC50 of 1.5 nM.
IC50 Value: 1.5 nM [1]
Target: FAK
in vitro: PND-1186 has an IC50 of ~100 nM in breast carcinoma cells as determined by anti-phospho-specific immunoblotting to FAK Tyr-397. PND-1186 did not alter c Src or p130Cas tyrosine phosphorylation in adherent cells, yet functioned to restrain cell movement. Notably, 1.0 ?M 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 [1].
in vivo: Addition of PND-1186 to the drinking water of mice was well tolerated and inhibited ascites- and peritoneal membrane-associated ovarian carcinoma tumor growth associated with the inhibition of FAK Tyr-397 phosphorylation [1]. PND-1186 (100 mg/kg intraperitoneal, i.p.) showed promising pharmacokinetics (PK) and inhibited tumor FAK Tyr-397 phosphorylation for 12 hours. Oral administration of 150 mg/kg PND-1186 gave a more sustained PK profile verses i.p., and when given twice daily, PND-1186 significantly inhibited sygeneic murine 4T1 orthotopic breast carcinoma tumor growth and spontaneous metastasis to lungs [2].
Clinical trial: Phase I, Dose-Escalation Study of VS-4718 in Subjects With Metastatic Non-Hematological Malignancies. Phase 1
 

[1]. Tanjoni I, et al. PND-1186 FAK inhibitor selectively promotes tumor cell apoptosis in three-dimensional environments. Cancer Biol Ther. 2010 May 15;9(10):764-77.

[2]. Walsh C, et al. Oral delivery of PND-1186 FAK inhibitor decreases tumor growth and spontaneous breast to lung metastasis in pre-clinical models. Cancer Biol Ther. 2010 May 15;9(10):778-90.