BMS-833923 is an inhibitor of Smoothened with potential antineoplastic activity. It can also inhibit BODIPY cyclopamine binding to SMO with IC50 of 21 nM.
The Hedgehog (Hh) pathway plays an important role in embryonic development and adult tissue maintenance via the regulation of cell differentiation and proliferation. Smoothened (Smo), a member of the GPCR superfamily, belongs to class F (Frizzled family) and is the main transducer of the Hh signaling pathway. BMS-833923 (XL 139) is an inhibitor of Smoothened with potential antineoplastic activity. Esophageal adenocarcinoma (EAC) cell lines OE19 and OE33 treated with 10 μM and 25 μM BMS-833923 showed 50% and 100% cell death, and caspase-3 was activated in 25 μM BMS-833923-treated group. Hh targeted gene Gli1 in the nuclear fraction was significantly decreased in both cell lines treated with 10 μM BMS-833923 compared to untreated cells[3]. BMS-833923 (30 mg/kg) monotherapy for 7 days in nu/nu mice xenograft model of cholangiocarcinoma resulted in a reduction of tumor volume (60% ± 23%) but the most pronounced size reduction could be seen in the gemcitabine (40 mg/kg)/BMS-833923 combination group (32% ± 5%)[4].
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