ILK-IN-2 (OSU-T315) is a novel potent, orally active ILK (integrin-linked kinase) inhibitor with IC50 of 0.6 μM.

ILK:0.6 μM

ILK-IN-25 exhibited high in vitro potency against a panel of prostate and breast cancer cell lines (IC(50), 1-2.5 μM), while normal epithelial cells were unaffected. ILK-IN-25 facilitated the dephosphorylation of Akt at Ser-473 and other ILK targets, including glycogen synthase kinase-3β and myosin light chain. Moreover, ILK-IN-25 suppressed the expression of the transcription/translation factor YB-1 and its targets HER2 and EGFR in PC-3 cells, which could be rescued by the stable expression of constitutively active ILK [1]. The cytotoxicity of ILK-IN-25 in normal B or T cells was significantly lower (LC50 > 10 μM). ILK-IN-25 had the effect of dose-dependent cytotoxicity toward 2 CLL-derived cell lines, Mec-1 and OSU-CLL (LC50 of 2-3 μM in both) after 24-hour treatment [2].

Athymic nude mice bearing established subcutaneous PC-3 tumors were treated with oral ILK-IN-25 once daily at 25 and 50 mg/kg or vehicle control. The daily administration of ILK-IN-25 at both doses was well tolerated. Treatment with oral ILK-IN-25 in either dose resulted in significant suppression of tumor growth relative to the vehicle control after 35 days of treatment (48% and 62% suppression for 25 and 50 mg/kg, respectively) [1].