Vismodegib

A potent and selective Hedgehog (Hh) pathway signaling inhibitor antagonizing SMO with a Ki of 1.3 nM) [1]. Alters intracellular Ca2+ homeostasis and inhibits growth of cisplatin-resistant lung cancer cells [2]. Inhibits two ABC transporters, ABCG2/BCRP and ABCB1/Pgp, IC50s=1.4 and 3.0 μM respectively [3]. Clinically useful for the treatment of basal cell carcinoma [4]. Inhibits proliferation and induces apoptosis in colon cancer cell lines.

References:

1) Rominger et al. (2009), Evidence for allosteric interactions of antagonist binding to the smoothened receptor;  J. Pharmacol. Exp. Therap., 329 995

2) Tian et al. (2012), the hedgehog pathway inhibitor GDC-0449 alters intracellular Ca2+ homeostasis and inhibits cell growth in cisplatin-resistant lung cancer cells;  Anticancer Res., 32 89

3) Zhang et al. (2009), Hedgehog pathway inhibitor HhAntag691 is a potent inhibitor of ABCG2/BCRP and ABCB1/Pgp;  Neoplasia, 11 96

4) Cirrone and Harris (2012), Vismodegib anf the hedgehog pathway: a new treatment for basal cell carcinoma;  Clin. Ther., 34 2039