BMS-833923 (XL-139)
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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.


Chemical Structure

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BMS-833923 (XL-139)
CAS# 1059734-66-5

Theoretical Analysis

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

Price and Availability

Size Price Availability Quantity
25.0mg USD 150.0 Same day
50.0mg USD 250.0 Same day
100.0mg USD 450.0 Same day
200.0mg USD 750.0 Same day
500.0mg USD 1250.0 Same day
1.0g USD 1950.0 2 weeks
2.0g USD 2950.0 2 weeks
5.0g USD 4950.0 2 weeks
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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/

Solubility Data

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

Preparing Stock Solutions

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.

Recalculate based on batch purity %
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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1: Wilkinson SE, Furic L, Buchanan G, Larsson O, Pedersen J, Frydenberg M, Risbridger GP, Taylor RA. Hedgehog signaling is active in human prostate cancer stroma and regulates proliferation and differentiation of adjacent epithelium. Prostate. 2013 Dec;73(16):1810-23. doi: 10.1002/pros.22720. Epub 2013 Sep 16. PubMed PMID: 24105601.

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. PubMed PMID: 23915072.

3: Sandhiya S, Melvin G, Kumar SS, Dkhar SA. The dawn of hedgehog inhibitors: Vismodegib. J Pharmacol Pharmacother. 2013 Jan;4(1):4-7. doi: 10.4103/0976-500X.107628. PubMed PMID: 23662017; PubMed Central PMCID: PMC3643342.

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5: Gibson MK, Zaidi AH, Davison JM, Sanz AF, Hough B, Komatsu Y, Kosovec JE, Bhatt A, Malhotra U, Foxwell T, Rotoloni CL, Hoppo T, Jobe BA. Prevention of Barrett esophagus and esophageal adenocarcinoma by smoothened inhibitor in a rat model of gastroesophageal reflux disease. Ann Surg. 2013 Jul;258(1):82-8. doi: 10.1097/SLA.0b013e318270500d. PubMed PMID: 23108119.

6: Cortes J, Goldman JM, Hughes T. Current issues in chronic myeloid leukemia: monitoring, resistance, and functional cure. J Natl Compr Canc Netw. 2012 Oct 1;10 Suppl 3:S1-S13. PubMed PMID: 23055247.

7: Tang JY, Marghoob AA. Emerging treatments and signaling pathway inhibitors. Semin Cutan Med Surg. 2011 Dec;30(4 Suppl):S14-8. doi: 10.1016/j.sder.2011.11.002. Review. PubMed PMID: 22177102.



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