JNJ-7706621

• CAT Number: I003572
• CAS Number: 443797-96-4
• Molecular Formula: C₁₅H₁₂F₂N₆O₃S
• Molecular Weight: 394.36
• Purity: ≥95%
• Target: Aurora Kinase
• Solubility: DMSO ≥75mg/mL Water <1.2mg/mL Ethanol ≥2.8mg/mL
• Storage: 3 years -20C powder
• IC50: 9 nM(CDK1/Cyclin B); 4 nM(CDK2/Cyclin A); 3 nM(CDK2/Cyclin E); 11 nM (Aurora-A)
• InChI: InChI=1S/C15H12F2N6O3S/c16-10-2-1-3-11(17)12(10)13(24)23-14(18)21-15(22-23)20-8-4-6-9(7-5-8)27(19,25)26/h1-7H,(H2,19,25,26)(H3,18,20,21,22)
• InChIKey: KDKUVYLMPJIGKA-UHFFFAOYSA-N
• SMILES: C1=CC(=C(C(=C1)F)C(=O)N2C(=NC(=N2)NC3=CC=C(C=C3)S(=O)(=O)N)N)F

JNJ-7706621 is pan-CDK inhibitor with the highest potency on CDK1/2 with IC50 of 9 nM/4 nM and showing >6-fold selectivity for CDK1/2 than CDK3/4/6; also potently inhibits Aurora A/B and has no activity on Plk1 and Wee1.IC50 Value: 9 nM(CDK1/Cyclin B); 4 nM(CDK2/Cyclin A); 3 nM(CDK2/Cyclin E); 11 nM (Aurora-A)Target: CDK1/2; Aurora A/Bin vitro: JNJ-7706621 shows some inhibition to VEGF-R2, FGF-R2, and GSK3β, with IC50 of 154-254 nM. JNJ-7706621 shows inhibitory effect on a panel of human cancer cell types, including HeLa, HCT-116, SK-OV-3, PC3, DU145, A375, MDA-MB-231, MES-SA, and MES-SA/Dx5, with IC50 of 112-514 nM, independent of p53, retinoblastoma, or P-glycoprotein status. JNJ-7706621 is several-fold less potent at inhibiting growth of normal cell types, including MRC-5, HASMC, HUVEC, and HMVEC, with IC50 of 3.67-5.42 μM. In HeLa or U937 cells, JNJ-7706621 (0.5-3 μM) delays exit from G1, arrests cells in G2-M, induces endoreduplication, activates apoptosis, and reduces colony formation. In a HeLa cell line, incremental treatment with increasing concentrations of JNJ-7706621 leads to a 16-fold resistance, which may be mediated by ABCG2.in vivo: In mouse xenograft model of A375 melanoma human tumor, JNJ-7706621 (100 or 125 mg/kg) causes tumor regression.

Reference

1:Growth suppression and mitotic defect induced by JNJ-7706621, an inhibitor of cyclin-dependent kinases and aurora kinases. Matsuhashi A, Ohno T, Kimura M, Hara A, Saio M, Nagano A, Kawai G, Saitou M, Takigami I, Yamada K, Okano Y, Shimizu K.Curr Cancer Drug Targets. 2012 Jul;12(6):625-39. PMID: 22463590 2:Active and passive tumor targeting of a novel poorly soluble cyclin dependent kinase inhibitor, JNJ-7706621. Danhier F, Ucakar B, Magotteaux N, Brewster ME, Préat V.Int J Pharm. 2010 Jun 15;392(1-2):20-8. doi: 10.1016/j.ijpharm.2010.03.018. Epub 2010 Mar 11. PMID: 20226846 3:Synthesis and evaluation of N-acyl sulfonamides as potential prodrugs of cyclin-dependent kinase inhibitor JNJ-7706621. Huang S, Connolly PJ, Lin R, Emanuel S, Middleton SA.Bioorg Med Chem Lett. 2006 Jul 15;16(14):3639-41. Epub 2006 May 6. PMID: 16682186 4:The in vitro and in vivo effects of JNJ-7706621: a dual inhibitor of cyclin-dependent kinases and aurora kinases. Emanuel S, Rugg CA, Gruninger RH, Lin R, Fuentes-Pesquera A, Connolly PJ, Wetter SK, Hollister B, Kruger WW, Napier C, Jolliffe L, Middleton SA.Cancer Res. 2005 Oct 1;65(19):9038-46. PMID: 16204078 Free Article