Biological Activity of BMS-833923

Description:
IC50 Value: 6-35 nM [1]
BMS-833923 (or XL-139) is an orally bioavailable small-molecule SMO (Smoothened) inhibitor with potential antineoplastic activity. SMO antagonist BMS-833923 inhibits the sonic hedgehog (SHH) pathway protein SMO, which may result in a suppression of the SHH signaling pathway.
in vitro: In vitro, BMS-833923 inhibits the expression of downstream effectors in the HH pathway (GLI1 and PTCH1) in cell lines that express wild-type SMO and those which express activated mutant forms of SMO (IC50values of 6-35 nM). In FACS-based binding assays, BMS-833923 inhibits BODIPY cyclopamine binding to SMO in a dose-dependent manner with an IC50 of 21 nM [1].
in vivo: Pharmacodynamic studies show that BMS-833923 robustly inhibits HH pathway activity with along duration of action after a single oral dose in medulloblastoma and pancreatic carcinoma xenograft models. The pharmacodynamic effects of BMS-833923 observed in these models translate into tumor growth inhibition at well-tolerated doses [1].
Clinical trial: Dasatinib Combo With Smoothened (SMO) Antagonist (BMS-833923). Phase 2