product name BMS-833923
Description: BMS-833923 (also known as XL-139) is a potent, selective, and orally bioavailable small-molecule SMO (Smoothened) inhibitor with potential antineoplastic activity. BMS-833923 inhibits the sonic hedgehog (SHH) pathway protein SMO, which may result in a suppression of the SHH signaling pathway. BMS-833923 robustly inhibits HH pathway activity with along duration of action after a single oral dose in medulloblastoma and pancreatic carcinoma xenograft models.
References: Cancer Invest. 2013 Aug;31(7):480-9; Prostate. 2013 Dec;73(16):1810-23.
473.57
Formula
C30H27N5O
CAS No.
1059734-66-5
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 95 mg/mL (200.6 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
XL139
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19426294
| In Vitro |
In vitro activity: BMS-833923 reduces hedgehog pathway activity, decreases cell proliferation and induces apoptosis via the intrinsic pathway in esophageal adenocarcinoma (EAC) cell lines. BMS-833923 dose-dependently affects canonical and prostate hedgehog signature gene transcription in vitro. Kinase Assay: Cell Assay: BMS-833923 inhibited the expression of GLI1 and PTCH1 in cell lines expressing wild-type SMO or activated mutant SMO with IC50 values in the range from 6 to 35 nM. In the FACS-based binding assays, it does-dependently suppressed cyclopamine binding to SMO with IC50 value of 21 nM. In the esophageal adenocarcinoma cell lines OE19 and OE33, treatment of BMS-833923 significantly reduced cell proliferation with IC50 values of both 10 μM. Besides that, BMS-833923 was found to inhibit the growth of multiple myeloma cells and the proportion of ALDH+ cancer stem cells. It also inhibited the growth of many other tumor cells derived from patients with hematological malignancies including ALL, AML and CM. |
|---|---|
| In Vivo | In animal models with medulloblastoma and pancreatic carcinoma xenografts, administration of BMS-833923 at single oral dose showed robust inhibition of Hh pathway. In a rat model with gastroesophageal reflux disease, the administration of BMS-833923 at dose of 10 mg/kg/day resulted in the decreased development of both Barrett esophagus and esophageal adenocarcinoma by 35.7%. |
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| Formulation & Dosage | |
| References | Cancer Invest. 2013 Aug;31(7):480-9; Prostate. 2013 Dec;73(16):1810-23. |
