tcsc0255 Vismodegib

Vismodegib is an orally active hedgehog pathway inhibitor with an IC₅₀ of 3 nM and also inhibits P-gp, ABCG2 with IC₅₀ values of 3.0 μM and 1.4 μM, respectively.

IC50 & Target: IC50: 3 nM (hedgehog), 3.0 μM (P-gp), 1.4 μM (ABCG2)

In Vitro: Vismodegib (HhAntag691) is an ABCG2 inhibitor and can increase the effective intracellular concentration of mitoxantrone, another ABCG2 substrate, through blocking its export in HEK293 cells. Vismodegib (HhAntag691, 10 µM), resensitizes MDCKII/Pgp cells and MDCKII/MRP1 cells to colchicine treatment^[2]. Vismodegib (25 μM or 50 μM) concentration dependently inhibits HCC and H1339 cells^[3].

In Vivo: Vismodegib is a novel small molecule HPI, often used for clinical trials^[1]. Vismodegib (0.3 to 75 mg/kg, p.o.) is highly efficacious in medulloblastoma allograft tumors. Vismodegib (> 46 mg/kg, p.o.) causes growth delay in patient-derived colorectal xenografts^[4].