SGX-523 | CAS#1022150-57-7 | MET inhibitor

MedKoo Cat#: 205715 | Name: SGX-523

Description:

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

SGX-523 is a novel, ATP-competitive kinase inhibitor remarkable for its exquisite selectivity for MET. SGX-523 potently inhibited MET with an IC50 of 4 nmol/L and is >1,000-fold selective versus the >200-fold selectivity of other protein kinases tested in biochemical assays. Crystallographic study revealed that SGX-523 stabilizes MET in a unique inactive conformation that is inaccessible to other protein kinases, suggesting an explanation for the selectivity. SGX-523 inhibited MET-mediated signaling, cell proliferation, and cell migration at nanomolar concentrations but had no effect on signaling dependent on other protein kinases, including the closely related RON, even at micromolar concentrations.

Chemical Structure

SGX-523

CAS#1022150-57-7

Theoretical Analysis

MedKoo Cat#: 205715

Name: SGX-523

CAS#: 1022150-57-7

Chemical Formula: C18H13N7S

Exact Mass: 359.0953

Molecular Weight: 359.41

Elemental Analysis: C, 60.15; H, 3.65; N, 27.28; S, 8.92

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 300.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,150.00	Ready to ship
1g	USD 3,650.00	2 Weeks

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Related CAS #

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Synonym

SGX523; SGX-523; SGX523.

IUPAC/Chemical Name

6-((6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)thio)quinoline

InChi Key

BCZUAADEACICHN-UHFFFAOYSA-N

InChi Code

InChI=1S/C18H13N7S/c1-24-11-13(10-20-24)16-6-7-17-21-22-18(25(17)23-16)26-14-4-5-15-12(9-14)3-2-8-19-15/h2-11H,1H3

SMILES Code

CN1N=CC(C2=NN3C(C=C2)=NN=C3SC4=CC=C5N=CC=CC5=C4)=C1

Appearance

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#CRB50724

QC Data

View QC data: current batch, Lot#CRB50724

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

SGX-523 is a selective MET inhibitor with an IC50 of 4 nM.

In vitro activity:

MET inhibition efficacy by SGX523 and EGFR-MET heterodimerization depends on the EGFR genotype, potentially influencing treatment outcomes due to its role in modulating tumor behavior. SGX523 significantly reduced H1975L858R/T790M cell proliferation and decreased ERK phosphorylation. This was not seen in H1975L858R or H1975WT cells. SGX523 only reduced stroma formation in H1975L858R. SGX523 reduced EGFR-MET dimerization in H1975L858R/T790M but induced dimer formation in H1975L858R with no effect in H1975WT Reference: PLoS One. 2017 Jan 31;12(1):e0170798. https://pubmed.ncbi.nlm.nih.gov/28141869/

In vivo activity:

Selective inhibition of MET kinase activity effectively hinders the growth of tumors activated by distinct MET activation mechanisms. SGX-523, administered to nude mice, exhibited potent inhibition of tumor growth at 10 mg/kg and induced clear regression at 30 mg/kg for U87MG tumors. In H441 tumors, dosing twice daily at 30 mg/kg also retarded growth with a concurrent reduction in tumor MET autophosphorylation levels. Reference: Mol Cancer Ther. 2009 Dec;8(12):3181-90. https://pubmed.ncbi.nlm.nih.gov/19934279/

	Solvent	mg/mL	mM
Solubility
	DMSO	10.1	28.10
	DMF	0.3	0.83

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 359.41 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. Zhang YW, Staal B, Essenburg C, Su Y, Kang L, West R, Kaufman D, Dekoning T, Eagleson B, Buchanan SG, Vande Woude GF. MET kinase inhibitor SGX523 synergizes with epidermal growth factor receptor inhibitor erlotinib in a hepatocyte growth factor-dependent fashion to suppress carcinoma growth. Cancer Res. 2010 Sep 1;70(17):6880-90. doi: 10.1158/0008-5472.CAN-10-0898. Epub 2010 Jul 19. Erratum in: Cancer Res. 2011 Apr 1;71(7):2804. PMID: 20643778. 2. Ortiz-Zapater E, Lee RW, Owen W, Weitsman G, Fruhwirth G, Dunn RG, Neat MJ, McCaughan F, Parker P, Ng T, Santis G. MET-EGFR dimerization in lung adenocarcinoma is dependent on EGFR mtations and altered by MET kinase inhibition. PLoS One. 2017 Jan 31;12(1):e0170798. doi: 10.1371/journal.pone.0170798. PMID: 28141869; PMCID: PMC5283661. 3. Cheng Z, Liu L, Zhang XJ, Lu M, Wang Y, Assfalg V, Laschinger M, von Figura G, Sunami Y, Michalski CW, Kleeff J, Friess H, Hartmann D, Hüser N. Peroxisome Proliferator-Activated Receptor gamma negatively regulates liver regeneration after partial hepatectomy via the HGF/c-Met/ERK1/2 pathways. Sci Rep. 2018 Aug 8;8(1):11894. doi: 10.1038/s41598-018-30426-5. PMID: 30089804; PMCID: PMC6082852. 4. Buchanan SG, Hendle J, Lee PS, Smith CR, Bounaud PY, Jessen KA, Tang CM, Huser NH, Felce JD, Froning KJ, Peterman MC, Aubol BE, Gessert SF, Sauder JM, Schwinn KD, Russell M, Rooney IA, Adams J, Leon BC, Do TH, Blaney JM, Sprengeler PA, Thompson DA, Smyth L, Pelletier LA, Atwell S, Holme K, Wasserman SR, Emtage S, Burley SK, Reich SH. SGX523 is an exquisitely selective, ATP-competitive inhibitor of the MET receptor tyrosine kinase with antitumor activity in vivo. Mol Cancer Ther. 2009 Dec;8(12):3181-90. doi: 10.1158/1535-7163.MCT-09-0477. PMID: 19934279.

In vitro protocol:

In vivo protocol:

1. Cheng Z, Liu L, Zhang XJ, Lu M, Wang Y, Assfalg V, Laschinger M, von Figura G, Sunami Y, Michalski CW, Kleeff J, Friess H, Hartmann D, Hüser N. Peroxisome Proliferator-Activated Receptor gamma negatively regulates liver regeneration after partial hepatectomy via the HGF/c-Met/ERK1/2 pathways. Sci Rep. 2018 Aug 8;8(1):11894. doi: 10.1038/s41598-018-30426-5. PMID: 30089804; PMCID: PMC6082852. 2. Buchanan SG, Hendle J, Lee PS, Smith CR, Bounaud PY, Jessen KA, Tang CM, Huser NH, Felce JD, Froning KJ, Peterman MC, Aubol BE, Gessert SF, Sauder JM, Schwinn KD, Russell M, Rooney IA, Adams J, Leon BC, Do TH, Blaney JM, Sprengeler PA, Thompson DA, Smyth L, Pelletier LA, Atwell S, Holme K, Wasserman SR, Emtage S, Burley SK, Reich SH. SGX523 is an exquisitely selective, ATP-competitive inhibitor of the MET receptor tyrosine kinase with antitumor activity in vivo. Mol Cancer Ther. 2009 Dec;8(12):3181-90. doi: 10.1158/1535-7163.MCT-09-0477. PMID: 19934279.

1: Zhang YW, Staal B, Essenburg C, Lewis S, Kaufman D, Vande Woude GF. Strengthening context-dependent anticancer effects on non-small cell lung carcinoma by inhibition of both MET and EGFR. Mol Cancer Ther. 2013 Aug;12(8):1429-41. doi: 10.1158/1535-7163.MCT-13-0016. Epub 2013 May 29. PubMed PMID: 23720767. 2: Kawakami H, Okamoto I, Arao T, Okamoto W, Matsumoto K, Taniguchi H, Kuwata K, Yamaguchi H, Nishio K, Nakagawa K, Yamada Y. MET amplification as a potential therapeutic target in gastric cancer. Oncotarget. 2013 Jan;4(1):9-17. PubMed PMID: 23327903; PubMed Central PMCID: PMC3702203. 3: Infante JR, Rugg T, Gordon M, Rooney I, Rosen L, Zeh K, Liu R, Burris HA, Ramanathan RK. Unexpected renal toxicity associated with SGX523, a small molecule inhibitor of MET. Invest New Drugs. 2013 Apr;31(2):363-9. doi: 10.1007/s10637-012-9823-9. Epub 2012 May 1. PubMed PMID: 22547164. 4: Xie Q, Bradley R, Kang L, Koeman J, Ascierto ML, Worschech A, De Giorgi V, Wang E, Kefene L, Su Y, Essenburg C, Kaufman DW, DeKoning T, Enter MA, O'Rourke TJ, Marincola FM, Vande Woude GF. Hepatocyte growth factor (HGF) autocrine activation predicts sensitivity to MET inhibition in glioblastoma. Proc Natl Acad Sci U S A. 2012 Jan 10;109(2):570-5. doi: 10.1073/pnas.1119059109. Epub 2011 Dec 27. PubMed PMID: 22203985; PubMed Central PMCID: PMC3258605. 5: Zhang YW, Staal B, Essenburg C, Su Y, Kang L, West R, Kaufman D, Dekoning T, Eagleson B, Buchanan SG, Vande Woude GF. MET kinase inhibitor SGX523 synergizes with epidermal growth factor receptor inhibitor erlotinib in a hepatocyte growth factor-dependent fashion to suppress carcinoma growth. Cancer Res. 2010 Sep 1;70(17):6880-90. doi: 10.1158/0008-5472.CAN-10-0898. Epub 2010 Jul 19. Erratum in: Cancer Res. 2011 Apr 1;71(7):2804. PubMed PMID: 20643778. 6: Diamond S, Boer J, Maduskuie TP Jr, Falahatpisheh N, Li Y, Yeleswaram S. Species-specific metabolism of SGX523 by aldehyde oxidase and the toxicological implications. Drug Metab Dispos. 2010 Aug;38(8):1277-85. doi: 10.1124/dmd.110.032375. Epub 2010 Apr 26. PubMed PMID: 20421447. 7: Guessous F, Zhang Y, diPierro C, Marcinkiewicz L, Sarkaria J, Schiff D, Buchanan S, Abounader R. An orally bioavailable c-Met kinase inhibitor potently inhibits brain tumor malignancy and growth. Anticancer Agents Med Chem. 2010 Jan;10(1):28-35. PubMed PMID: 20015006; PubMed Central PMCID: PMC3278215. 8: Buchanan SG, Hendle J, Lee PS, Smith CR, Bounaud PY, Jessen KA, Tang CM, Huser NH, Felce JD, Froning KJ, Peterman MC, Aubol BE, Gessert SF, Sauder JM, Schwinn KD, Russell M, Rooney IA, Adams J, Leon BC, Do TH, Blaney JM, Sprengeler PA, Thompson DA, Smyth L, Pelletier LA, Atwell S, Holme K, Wasserman SR, Emtage S, Burley SK, Reich SH. SGX523 is an exquisitely selective, ATP-competitive inhibitor of the MET receptor tyrosine kinase with antitumor activity in vivo. Mol Cancer Ther. 2009 Dec;8(12):3181-90. doi: 10.1158/1535-7163.MCT-09-0477. Epub . PubMed PMID: 19934279