SU9516

• CAT Number: I003386
• CAS Number: 377090-84-1
• Molecular Formula: C13H11N3O2
• Molecular Weight: 241.3
• Purity: ≥95%
• Target: Cyclin-Dependent Kinases
• Solubility: 10 mM in DMSO
• Storage: Store at 4°C
• IC50: 22 nM/40 nM(CDK2/CDK1) [1]
• InChIKey: QNUKRWAIZMBVCU-WCIBSUBMSA-N

SU-9516 is a selective CDK2 inhibtor with IC50 of 22 nM; less potent for CDK1/CDK4(IC50=40/200 nM), no inhibition on PKC, EGFR, p38MAPK etc.IC50 value: 22 nM/40 nM(CDK2/CDK1) [1]Target: CDK2 inhibitorin vitro: SU9516 is a potent inhibitor for cdk 2 and that it is 9-fold and 1.8-fold more selective for cdk2 than cdk4 and cdk1, respectively. Treatment with SU9516 (5 μM) inhibited (P ≤ 0.05) both cdk2-specific (27–64%) and cdk4-specific (26–49%) phosphorylation of pRb in SW480 cells at all (24, 48, and 72 h) time points. RKO cells remained blocked in G2-M at 20 h post-serum induction and -addition of SU9516. SU9516 produced a dose-dependent G1 accumulation in EGF-stimulated cells [1]. Treatment with 5 microM SU9516 prevented dissociation of pRb from E2F1 in all cell lines (HT-29>RKO>SW480). Treatment effects were time-dependent, demonstrating greater inhibition at 48 hr versus 24hr in HT-29 cells. Furthermore, E2F species were sequestered in complexes with p107, p130, DP-1, and cyclins A and E. After a 24-hr treatment with 5 microM SU9516, cyclin D1 and cdk2 levels decreased by 10-60% [2]. Exposure of U937 and other leukemia cells to SU9516 concentrations > or =5 microM rapidly (i.e., within 4 h) induced cytochrome c release, Bax mitochondrial translocation, and apoptosis in association with pronounced down-regulation of the antiapoptotic protein Mcl-1 [3].in vivo:

Reference

1:SU9516 Increases α7β1 Integrin and Ameliorates Disease Progression in the mdx Mouse Model of Duchenne Muscular Dystrophy. Sarathy A, Wuebbles RD, Fontelonga TM, Tarchione AR, Mathews Griner LA, Heredia DJ, Nunes AM, Duan S, Brewer PD, Van Ry T, Hennig GW, Gould TW, Dulcey AE, Wang A, Xu X, Chen CZ, Hu X, Zheng W, Southall N, Ferrer M, Marugan J, Burkin DJ.Mol Ther. 2017 Apr 5. pii: S1525-0016(17)30121-1. doi: 10.1016/j.ymthe.2017.03.022. [Epub ahead of print] PMID: 28391962 2:CDK inhibitor SU9516 induces tetraploid blastocyst formation from parthenogenetically activated porcine embryos. Guo Q, Jin L, Zhu HY, Li XC, Zhang YC, Xing XX, Zhang GL, Xuan MF, Luo QR, Luo ZB, Wang JX, Kang JD, Yin XJ.Biotechnol Lett. 2017 Mar 17. doi: 10.1007/s10529-017-2321-6. [Epub ahead of print] PMID: 28315059 3:A Novel High-Throughput 3D Screening System for EMT Inhibitors: A Pilot Screening Discovered the EMT Inhibitory Activity of CDK2 Inhibitor SU9516. Arai K, Eguchi T, Rahman MM, Sakamoto R, Masuda N, Nakatsura T, Calderwood SK, Kozaki K, Itoh M.PLoS One. 2016 Sep 13;11(9):e0162394. doi: 10.1371/journal.pone.0162394. eCollection 2016. PMID: 27622654 Free PMC Article4:Cyclin-dependent kinase inhibitor SU9516 enhances sensitivity to methotrexate in human T-cell leukemia Jurkat cells. Uchiyama H, Sowa Y, Wakada M, Yogosawa M, Nakanishi R, Horinaka M, Shimazaki C, Taniwaki M, Sakai T.Cancer Sci. 2010 Mar;101(3):728-34. doi: 10.1111/j.1349-7006.2009.01449.x. Epub 2009 Nov 27. PMID: 20059476 Free Article5:The three-substituted indolinone cyclin-dependent kinase 2 inhibitor 3-[1-(3H-imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one (SU9516) kills human leukemia cells via down-regulation of Mcl-1 through a transcriptional mechanism. Gao N, Kramer L, Rahmani M, Dent P, Grant S.Mol Pharmacol. 2006 Aug;70(2):645-55. Epub 2006 May 3. PMID: 16672643 Free Article6:SU9516: biochemical analysis of cdk inhibition and crystal structure in complex with cdk2. Moshinsky DJ, Bellamacina CR, Boisvert DC, Huang P, Hui T, Jancarik J, Kim SH, Rice AG.Biochem Biophys Res Commun. 2003 Oct 24;310(3):1026-31. PMID: 14550307 7:SU9516, a cyclin-dependent kinase 2 inhibitor, promotes accumulation of high molecular weight E2F complexes in human colon carcinoma cells. Yu B, Lane ME, Wadler S.Biochem Pharmacol. 2002 Oct 1;64(7):1091-100. PMID: 12234612 8:A novel cdk2-selective inhibitor, SU9516, induces apoptosis in colon carcinoma cells. Lane ME, Yu B, Rice A, Lipson KE, Liang C, Sun L, Tang C, McMahon G, Pestell RG, Wadler S.Cancer Res. 2001 Aug 15;61(16):6170-7. PMID: 11507069 Free Article