WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205715
Description: SGX523 is a novel, ATP-competitive kinase inhibitor remarkable for its exquisite selectivity for MET. SGX523 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 SGX523 stabilizes MET in a unique inactive conformation that is inaccessible to other protein kinases, suggesting an explanation for the selectivity. SGX523 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.
MedKoo Cat#: 205715
Chemical Formula: C18H13N7S
Exact Mass: 359.09531
Molecular Weight: 359.41
Elemental Analysis: C, 60.15; H, 3.65; N, 27.28; S, 8.92
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
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|
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