Inolitazone (RS5444) a high-affinity PPARγ agonist. Inolitazone exhibits IC50 for growth inhibition is ~0.8 nM in vitro.

Inolitazone (10 nM) inhibits the growth of DRO cells through a PPARγ-dependent mechanism[1]. Inolitazone upregulates the cell cycle kinase inhibitor, p21WAF1/CIP1. Inolitazone (10 nM) activates PPARγ:RXRα-dependent transcription utilizing a PPRE response element fused to a luciferase reporter gene (PPRE3-tk-luc). Inolitazone specifically activates PPARγ, but not PPARα or PPARδ. Inolitazone (10 nM) following transient transfection with the appropriate PPAR isoform (γ, α, or δ) and PPAR response element linked to a luciferase reporter in RIE rat small intestinal cell line, which does not express PPARs, yields increased luciferase activity only in the presence of PPARγ and PPRE3-tk-luc[2].

In athymic nude mice prior to DRO tumor cell implantation, Inolitazone inhibits tumor growth in a dose responsive fashion. 0.025% Inolitazone inhibits growth on day 32 by 94.4%. In the 0.0025% treatment group, tumor growth is inhibited by 62.3% while the 0.00025% dose demonstrated no growth inhibitory activity as compared to control. Inolitazone treated animals demonstrate tumor growth inhibition of 68.9% in DRO tumors and 48.3% in ARO tumors on day 35. Inolitazone plus Paclitaxel demonstrate additive antiproliferative activity in cell culture and minimal ATC tumor growth[1].