BMS-833923 | XL-139 | CAS#1059734-66-5

MedKoo Cat#: 200535 | Name: BMS-833923 (XL-139)

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

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

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: 473.2216

Molecular Weight: 473.57

Elemental Analysis: C, 76.09; H, 5.75; N, 14.79; O, 3.38

Price and Availability

Size	Price	Availability
10mg	USD 110.00	Ready to ship
25mg	USD 220.00	Ready to ship
50mg	USD 350.00	Ready to ship
100mg	USD 600.00	Ready to ship
200mg	USD 1,050.00	Ready to ship
500mg	USD 2,150.00	Ready to ship
1g	USD 3,450.00	2 weeks
2g	USD 5,850.00	2 weeks

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Related CAS #

No Data

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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#CRB40331

QC Data

View QC data: current batch, Lot#CRB40331

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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	mg/mL	mM
Solubility
	DMSO	56.7	119.67
	DMF	30.0	63.35
	Ethanol	30.0	63.35
	Ethanol:PBS (pH 7.2) (1:7)	0.1	0.21

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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.

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:

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.

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. 4: Ali FR, Lear JT. Systemic treatments for basal cell carcinoma (BCC): the advent of dermato-oncology in BCC. Br J Dermatol. 2013 Jul;169(1):53-7. doi: 10.1111/bjd.12311. Review. PubMed PMID: 23488543. 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.