BMS-833923

BMS-833923 (XL-139) is an orally biocompatible Smoothened (Smo) inhibitor with anti-tumor activity. It can inhibit the binding of BODIPY cyclopamine to SMO in a dose-dependent manner with an IC₅₀ of 21 nM^[1]. In Vitro:BMS‐833923 inhibits the expression of downstream effectors in the HH pathway (GLI1 and PTCH1) wild‐type SMO and activated mutant forms of SMO expressing cells (IC₅₀: 6-35 nM)^[1].
BMS‐833923 (2.5-10 μM, 48 h) inhibits cell proliferation of both A549 and H1299 cells^[2].
BMS‐833923 (3 µM) inhibits osteoblast differentiation and mineralization of hMSCs, determined by decreased ALP activity and downregulation of osteoblast-related gene expression^[3].
In Vivo:BMS-833923 (15 mg/kg, oral gavage, daily) alone or together with Selumetinib (HY-50706) (10 mg/kg, oral gavage, daily) reduces tumor metastasis and the post-extravasation tumor growth in orthotopic mouse model of pancreatic cancer metastasis^[4].
BMS-833923 (30 mg/kg, p.o., seven consecutive days) alone or together with Gemcitabine (HY-17026) (40 mg/kg, i.p., at the 1st, 4th and 7th day) reduces tumor volume (to 60% and 32% respectively) in a nu/nu mice xenograft model of cholangiocarcinoma^[5].