A939572

A939572 is a potent, and orally bioavailable stearoyl-CoA desaturase1 (SCD1) inhibitor with IC₅₀ values of <4 nM and 37 nM for mSCD1 and hSCD1, respectively. IC50 & Target: IC50: <4 nM (mSCD1), 37 nM (hSCD1)^[1] In Vitro: A939572 exhibits robust in vivo activity with dose-dependent desaturation index lowering effects^[1]. A939572 is a small molecule that specifically inhibits SCD1 enzymatic activity. A939572 demonstrates a significant dose-dependent decrease in proliferation in Caki1, A498, Caki2, and ACHN at day 5 (IC₅₀s of 65 nM, 50 nM, 65 nM, and 6 nM, respectively). In A939572 (SCDi) treated Caki1 and A498 cells, all five ER stress related genes are expressed at significantly increased levels compared to DMSO+BSA control, and this elevated expression can be blocked with the addition of OA-BSA^[2]. In Vivo: Athymic nude (nu/nu) mice bearing A498 ccRCC xenografts are treated with A939572 (30mg/kg, p.o.) and Tem individually or in combination over the course of four weeks, and tumor volume (mm³) is recorded. A939572 and Tem monotherapy generate similar growth responses with approximately 20-30% reductions in tumor volume (vs. placebo control) being observed upon study completion, with values reaching statistical significance only within the last week of treatment. The combination group yields over a 60% decrease in tumor volume (vs. placebo control) by study completion with significant reductions recorded after approximately 1 week of treatment^[2].