BioCentury
ARTICLE | Distillery Therapeutics

Cancer

September 19, 2017 7:21 PM UTC

In vitro and mouse studies identified a hedgehog pathway inhibitor that could help treat medulloblastoma. Optimization and testing in mouse fibroblast cell-based assays of a previously identified dihydrobenzooxazocin analog yielded a compound that inhibited the activity of the hedgehog pathway signaling component GLI1 with an IC50 of 23 nM. In cancer cells from a mouse model of medulloblastoma, the compound decreased proliferation and decreased expression of GLI1 and PTCH1, another hedgehog pathway component, with potencies comparable to the SMO antagonist Erivedge vismodegib. In an another mouse model of medulloblastoma, the compound decreased GL1 and PTCH1 expression and tumor growth and increased tumor cell apoptosis compared with vehicle, without causing substantial body weight loss. Next steps could include testing the compound in animal models of SMO-resistant medulloblastoma.

The Genentech Inc. unit of Roche, Chugai Pharmaceutical Co. Ltd. and Curis Inc. market Erivedge to treat basal cell carcinoma (BCC), and have the compound in Phase II testing to treat acute myelogenous leukemia (AML), bone cancer, medulloblastoma and pancreatic cancer and Phase I testing to treat sarcoma and myelofibrosis...