Vismodegib | CAS:879085-55-9

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Name:Vismodegib; GDC-0449
Cat. No. :CS-0255
CAS No. :879085-55-9
Formula:C19H14Cl2N2O3S
M. Wt. : 421.30
Solubility:10 mM in DMSO

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].

Wong H, et al. Pharmacokinetic-pharmacodynamic analysis of vismodegib in preclinical models of mutational and ligand-dependent Hedgehog pathway activation. Clin Cancer Res. 2011, 17(14), 4682-4692. Zhang Y, et al. Hedgehog pathway inhibitor HhAntag691 is a potent inhibitor of ABCG2/BCRP and ABCB1/Pgp. Neoplasia. 2009, 11(1), 96-101. Elhenawy AA, et al. Possible antifibrotic effect of GDC-0449 (Vismodegib), a hedgehog-pathway inhibitor, in mice model of Schistosoma-induced liver fibrosis. Parasitol Int. 2017 Oct;66(5):545-554. Scales SJ, et al. Mechanisms of Hedgehog pathway activation in cancer and implications for therapy. Trends Pharmacol Sci. 2009, 30(6), 303-312. Tian F, et al. The hedgehog pathway inhibitor GDC-0449 alters intracellular Ca2+ homeostasis and inhibits cell growth in cisplatin-resistant lung cancer cells. Anticancer Res. 2012, 32(1), 89-94.