SU6656

• CAT Number: I003183
• CAS Number: 330161-87-0
• Molecular Formula: C19H21N3O3S
• Molecular Weight: 371.5
• Purity: ≥95%
• Target: Src
• Solubility: DMSO :12 mg/ml
• Storage: Store at -20°C
• InChI: InChI=1S/C19H21N3O3S/c1-22(2)26(24,25)14-7-8-18-15(11-14)16(19(23)21-18)10-13-9-12-5-3-4-6-17(12)20-13/h7-11,20H,3-6H2,1-2H3,(H,21,23)/b16-10-
• InChIKey: LOGJQOUIVKBFGH-YBEGLDIGSA-N
• SMILES: O=C(/C1=CC2=CC3=C(CCCC3)N2)NC4=C1C=C(S(=O)(N(C)C)=O)C=C4

SU 6656 is a selective inhibitor of Src kinases, Including Src, Yes, Lyn, and Fyn (IC50 = 280, 20, 130, 170 nM, respectively).IC50 value:Target: Src kinases inhibitorin vitro: By comparing PDGF-stimulated tyrosine phosphorylation events in untreated and SU6656-treated cells, we found that some substrates (for example, c-Cbl, and protein kinase C delta) were Src family substrates whereas others (for example, phospholipase C-gamma) were not [1]. Selective inhibition of SFKs with SU6656 delocalized E-cadherin and disrupted cellular junctions without affecting E-cadherin expression and this effect was phenocopied by knockdown of Src or Yes [2]. Inhibiting Src kinase activity by SU6656 suppressed TGFβ-induced RhoA and ATF2 activation but not Smad2 phosphorylation [3]. SU6656, the selective inhibitor of the Src kinase activity, decreased up-regulation of the mTORC1 signalling and moreover, unlike rapamycin, it did not induce the activation of Akt/PKB and its downstream targets in HBL melanoma cells [4].in vivo: Ischemic postconditioning induced neuroprotective effects were significantly attenuated by pre-treatment of selective Src Kinase inhibitors SU-6656 (4 mg/kg i.p.) and PP1 (0.2 mg/kg i.p.) [5]. SU6656 and SKI-606 (bosutinib) enhanced immunotoxin killing of mesothelin-expressing cells by SS1P and CD22-expressing cells by HA22 (moxetumomab pasudotox). SU6656 also enhanced the antitumor effects of SS1P and HA22 in mouse xenograft tumor models [6].

Reference

1:Dual inhibition of Src family kinases and Aurora kinases by SU6656 modulates CTGF (connective tissue growth factor) expression in an ERK-dependent manner. Cicha I, Zitzmann R, Goppelt-Struebe M.Int J Biochem Cell Biol. 2014 Jan;46:39-48. doi: 10.1016/j.biocel.2013.11.014. Epub 2013 Nov 22. PMID: 24275091 2:Inhibition of mTORC1 by SU6656, the selective Src kinase inhibitor, is not accompanied by activation of Akt/PKB signalling in melanoma cells. Ondrušová L, Réda J, Záková P, Tuháčková Z.Folia Biol (Praha). 2013;59(4):162-7. PMID: 24093774 Free Article3:Inhibition of p21 and Akt potentiates SU6656-induced caspase-independent cell death in FRO anaplastic thyroid carcinoma cells. Kim SH, Kang JG, Kim CS, Ihm SH, Choi MG, Yoo HJ, Lee SJ.Horm Metab Res. 2013 Jun;45(6):408-14. doi: 10.1055/s-0033-1333716. Epub 2013 Feb 5. PMID: 23386415 4:Simultaneous inhibition of Src and Aurora kinases by SU6656 induces therapeutic synergy in human synovial sarcoma growth, invasion and angiogenesis in vivo. Arai R, Tsuda M, Watanabe T, Ose T, Obuse C, Maenaka K, Minami A, Ohba Y.Eur J Cancer. 2012 Oct;48(15):2417-30. doi: 10.1016/j.ejca.2011.12.028. Epub 2012 Jan 13. PMID: 22244830 5:Plasmodium induced by SU6656, an Src family kinase inhibitor, is accompanied by a contractile ring defect. Yoshida K, Ono M, Bito H, Mikami T, Sawada H.Cell Biochem Funct. 2012 Jan;30(1):33-40. doi: 10.1002/cbf.1814. Epub 2011 Oct 27. PMID: 22034098 6:Caspase-3-dependent mitotic checkpoint inactivation by the small-molecule inducers of mitotic slippage SU6656 and geraldol. Riffell JL, Jänicke RU, Roberge M.Mol Cancer Ther. 2011 May;10(5):839-49. doi: 10.1158/1535-7163.MCT-10-0909. Epub 2011 Mar 25. PMID: 21441410 Free Article7:Effects of inhibitor of Src kinases, SU6656, on differentiation of megakaryocytic progenitors and activity of alpha1,6-fucosyltransferase. Kaminska J, Klimczak-Jajor E, Skierski J, Bany-Laszewicz U.Acta Biochim Pol. 2008;55(3):499-506. Epub 2008 Sep 15. PMID: 18854874 Free Article8:Human B lymphocytes and non-Hodgkin/’s lymphoma cells become polyploid in response to the protein kinase inhibitor SU6656. Dussault N, Simard C, Néron S, Côté S.Blood Cells Mol Dis. 2007 Jul-Aug;39(1):130-4. Epub 2007 Apr 16. PMID: 17434768 9:SRC family kinase inhibitor SU6656 enhances antiangiogenic effect of irradiation. Cuneo KC, Geng L, Tan J, Brousal J, Shinohara ET, Osusky K, Fu A, Shyr Y, Wu H, Hallahan DE.Int J Radiat Oncol Biol Phys. 2006 Mar 15;64(4):1197-203. PMID: 16504759 10:Induction of polyploidization in leukemic cell lines and primary bone marrow by Src kinase inhibitor SU6656. Lannutti BJ, Blake N, Gandhi MJ, Reems JA, Drachman JG.Blood. 2005 May 15;105(10):3875-8. Epub 2005 Jan 27. PMID: 15677565 Free PMC Article