OSU-T315 (ILK-IN-1) is a small Integrin-linked kinase (ILK) inhibitor with an IC50 of 0.6 μM, inhibiting PI3K/AKT signaling by dephosphorylation of AKT-Ser473 and other ILK targets (GSK-3β and myosin light chain)[1]. OSU-T315 abrogates AKT activation by impeding AKT localization in lipid rafts and triggers caspase-dependent apoptosis in an ILK-independent manner[2]. OSU-T315 causes cell death through apoptosis and autophagy[1]. IC50: 0.6μM; Integrin-linked kinase (ILK) inhibitor[1]
OSU-T315 (Compound 22; 0-5 μM; 24 hours) exhibits high in vitro potency against a panel of prostate and breast cancer cell lines with a IC50 range of 1-2.5 μM[1].OSU-T315 (0-4 μM; 24 hours) can reduce YB-1, HER2, and EGFR expression; shows a modest suppressive effect on phosphorylated S6 levels, exhibits dose-dependent suppressive effects on the levels of phospho-ERK1/2 and phospho-p38, while that of phospho-JNK remains unaltered in PC-3 cell[1]. OSU-T315 (0-4 μM; 24 hours) causes autophagy through ILK inhibition[1]. Cell Viability Assay [1] Cell Line: Prostate cancer cells: LNCaP, PC-3; breast cancer cells: MDA-MB-231, MDA-MB-468, SKBR3, MCF-7; PrEC and MEC cells
OSU-T315 (Oral gavage; 25 mg/kg, 50 mg/kg; single daily; 35 days) has a suppressive effect of on PC-3 xenograft tumor growth [1]. No other obvious toxicity is observed in mice[1]. Animal Model: Male NCr athymic nude mice with PC-3 tumor xenografts
[1]. Su-Lin Lee,et al Identification and Characterization of a Novel Integrin-Linked Kinase Inhibitor.J Med Chem. 2011 Sep 22; 54(18): 6364-6374 [2]. Liu TM, et al. OSU-T315: a novel targeted therapeutic that antagonizes AKT membrane localization and activation of chronic lymphocytic leukemia cells. Blood. 2015 Jan 8;125(2):284-95.