Biological Activity
BMS-833923 (XL-139) is an orally bioavailable small-molecule inhibitor of Smoothened with potential antineoplastic activity; inhibits BODIPY cyclopamine binding to SMO in a dose-dependent manner with an IC50 of 21 nM.BMS-833923 inhibits the sonic hedgehog (SHH) pathway protein SMO, which may result in a suppression of the SHH signaling pathway.
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
References & source
1. Lee, H.K., Kim, H.W., Lee, I.Y., et al. G-749, a novel FLT3 kinase inhibitor, can overcome drug resistance for the treatment of acute myeloid leukemia. Blood 123(14), 2209-2219 (2014).
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.