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Hedgehog acyltransferase (HHAT); sonic hedgehog homolog (SHH); smoothened (SMO)

In vitro studies identified HHAT inhibitors that could help treat SHH-driven cancers. HHAT acts upstream of SMO in the hedgehog signaling pathway, potentially providing an alternative way to target the cancer-associated pathway. A high throughput screen identified hits that inhibited HHAT activity with low or submicromolar IC50 values. In cell lines, the lead inhibitor decreased SHH signaling compared with vehicle. Next steps include testing the HHAT inhibitors in preclinical models of SHH-driven cancers such as pancreatic cancer.
Erivedge vismodegib, a SMO inhibitor from Roche's Genentech Inc. unit and partners Chugai Pharmaceutical Co. Ltd. and Curis Inc., is marketed to treat basal cell carcinoma (BCC) and is in Phase II testing or earlier to treat other types of cancer.
At least four other companies have SMO inhibitors in Phase III testing or earlier to treat various cancers.

SciBX 6(9); doi:10.1038/scibx.2013.212
Published online March 7, 2013

Patent application filed; available for licensing

Petrova, E. et al. Nat. Chem. Biol.; published online Feb. 17, 2013;
Contact: Marilyn D. Resh, Memorial Sloan-Kettering Cancer Center,
New York, N.Y.