WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 200535
CAS#: 1059734-66-5
Description: BMS-833923, also known as 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. SMO is a G-protein coupled receptor that lies just downstream of the SHH ligand cell surface receptor Patched-1 in the SHH pathway; in the absence of ligand Patched-1 inhibits SMO and ligand binding to Patched-1 results in increased levels of SMO. The SHH signaling pathway plays an important role in cellular growth, differentiation and repair; constitutive activation of this pathway is associated with uncontrolled cellular proliferation and has been observed in a variety of cancers.
MedKoo Cat#: 200535
Name: BMS-833923 (XL-139)
CAS#: 1059734-66-5
Chemical Formula: C30H27N5O
Exact Mass: 473.22156
Molecular Weight: 473.57
Elemental Analysis: C, 76.09; H, 5.75; N, 14.79; O, 3.38
Synonym: BMS833923; BMS-833923; BMS 833923; XL139; XL-139; XL 139.
IUPAC/Chemical Name: N-(2-methyl-5-((methylamino)methyl)phenyl)-4-((4-phenylquinazolin-2-yl)amino)benzamide.
InChi Key: KLRRGBHZCJLIEL-UHFFFAOYSA-N
InChi Code: InChI=1S/C30H27N5O/c1-20-12-13-21(19-31-2)18-27(20)33-29(36)23-14-16-24(17-15-23)32-30-34-26-11-7-6-10-25(26)28(35-30)22-8-4-3-5-9-22/h3-18,31H,19H2,1-2H3,(H,33,36)(H,32,34,35)
SMILES Code: O=C(NC1=CC(CNC)=CC=C1C)C2=CC=C(NC3=NC(C4=CC=CC=C4)=C5C=CC=CC5=N3)C=C2.
Appearance: white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | BMS-833923 (XL-139) is an inhibitor of Smoothened with potential antineoplastic activity; inhibits BODIPY cyclopamine binding to SMO in a dose-dependent manner with an IC50 of 21 nM. |
| In vitro activity: | To identify if the growth inhibitory effect of the Smoothened antagonist BMS-833923 on EGI-1 cells is Hh dependent, this study measured the expression of the Hh target genes PTCH1 and GLI1 in the treated EGI-1 cells. Evaluation with the ΔΔCt method revealed a slight decrease in pathway gene expression levels in cell probes treated with BMS-833923. Forty-eight hours after incubation, expression levels of both pathway components were reduced compared to the control group (GLI1: RQ-value = 0.89; PTCH1: RQ-value = 0.76). The suppression of the Hh-signaling pathway components was even more pronounced in the samples that were collected after 96 h (GLI1: RQ-value = 0.71; PTCH1: RQ-value = 0.66) (Fig. 4). Reference: Stem Cells Int. 2019 Nov 21;2019:3435901. https://pubmed.ncbi.nlm.nih.gov/31871467/ |
| In vivo activity: | To further study the role of BMS-833923 in regulating osteoblast differentiation in vivo, this study determined the amount of bone formed in vivo by hMSCs treated with BMS-833923 or DMSO vehicle-treated control, following subcutaneous implantation into immune deficient mice. BMS-833923-treated hMSCs exhibited a significant reduction in ectopic bone formation capacity (Figures 5(a)–5(b)). Quantitative histological analysis revealed 90% (n = 3, P < 0.0001) reduction of bone area (Figure 5(c)) and 30% reduction in collagen matrix formation (n = 3, P < 0.001) (Figure 5(d)). Reference: Stem Cells Int. 2019; 2019: 3435901. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6907053/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 56.67 | 119.67 | |
| DMF | 30.0 | 63.35 | |
| Ethanol | 30.0 | 63.35 | |
| Ethanol:PBS (pH 7.2) (1:7) | 0.1 | 0.21 |
The following data is based on the product molecular weight 473.57 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. AlMuraikhi N, Almasoud N, Binhamdan S, Younis G, Ali D, Manikandan M, Vishnubalaji R, Atteya M, Siyal A, Alfayez M, Aldahmash A, Kassem M, Alajez NM. Hedgehog Signaling Inhibition by Smoothened Antagonist BMS-833923 Reduces Osteoblast Differentiation and Ectopic Bone Formation of Human Skeletal (Mesenchymal) Stem Cells. Stem Cells Int. 2019 Nov 21;2019:3435901. doi: 10.1155/2019/3435901. PMID: 31871467; PMCID: PMC6907053. 2. Zaidi AH, Komatsu Y, Kelly LA, Malhotra U, Rotoloni C, Kosovec JE, Zahoor H, Makielski R, Bhatt A, Hoppo T, Jobe BA. Smoothened inhibition leads to decreased proliferation and induces apoptosis in esophageal adenocarcinoma cells. Cancer Invest. 2013 Aug;31(7):480-9. doi: 10.3109/07357907.2013.820317. PMID: 23915072. 3. Riedlinger D, Bahra M, Boas-Knoop S, Lippert S, Bradtmöller M, Guse K, Seehofer D, Bova R, Sauer IM, Neuhaus P, Koch A, Kamphues C. Hedgehog pathway as a potential treatment target in human cholangiocarcinoma. J Hepatobiliary Pancreat Sci. 2014 Aug;21(8):607-15. doi: 10.1002/jhbp.107. Epub 2014 Apr 15. PMID: 24733827. |
| In vitro protocol: | 1. AlMuraikhi N, Almasoud N, Binhamdan S, Younis G, Ali D, Manikandan M, Vishnubalaji R, Atteya M, Siyal A, Alfayez M, Aldahmash A, Kassem M, Alajez NM. Hedgehog Signaling Inhibition by Smoothened Antagonist BMS-833923 Reduces Osteoblast Differentiation and Ectopic Bone Formation of Human Skeletal (Mesenchymal) Stem Cells. Stem Cells Int. 2019 Nov 21;2019:3435901. doi: 10.1155/2019/3435901. PMID: 31871467; PMCID: PMC6907053. 2. Zaidi AH, Komatsu Y, Kelly LA, Malhotra U, Rotoloni C, Kosovec JE, Zahoor H, Makielski R, Bhatt A, Hoppo T, Jobe BA. Smoothened inhibition leads to decreased proliferation and induces apoptosis in esophageal adenocarcinoma cells. Cancer Invest. 2013 Aug;31(7):480-9. doi: 10.3109/07357907.2013.820317. PMID: 23915072. |
| In vivo protocol: | 1. AlMuraikhi N, Almasoud N, Binhamdan S, Younis G, Ali D, Manikandan M, Vishnubalaji R, Atteya M, Siyal A, Alfayez M, Aldahmash A, Kassem M, Alajez NM. Hedgehog Signaling Inhibition by Smoothened Antagonist BMS-833923 Reduces Osteoblast Differentiation and Ectopic Bone Formation of Human Skeletal (Mesenchymal) Stem Cells. Stem Cells Int. 2019 Nov 21;2019:3435901. doi: 10.1155/2019/3435901. PMID: 31871467; PMCID: PMC6907053. 2. Riedlinger D, Bahra M, Boas-Knoop S, Lippert S, Bradtmöller M, Guse K, Seehofer D, Bova R, Sauer IM, Neuhaus P, Koch A, Kamphues C. Hedgehog pathway as a potential treatment target in human cholangiocarcinoma. J Hepatobiliary Pancreat Sci. 2014 Aug;21(8):607-15. doi: 10.1002/jhbp.107. Epub 2014 Apr 15. PMID: 24733827. |
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