For research use only. Not for therapeutic Use.
TAK-960 dihydrochloride is an orally available, selective inhibitor of polo-like kinase 1 (PLK1), with an IC50 of 0.8 nM. TAK-960 dihydrochloride also shows inhibitory activities against PLK2 and PLK3, with IC50s of 16.9 and 50.2 nM, respectively. TAK-960 dihydrochloride inhibits proliferation of multiple cancer cell lines and exhibits significant efficacy against multiple tumor xenografts[1].
TAK-960 dihydrochloride treatment causes accumulation of G2-M cells, aberrant polo mitosis morphology, and increased phosphorylation of histone H3 (pHH3). TAK-960 dihydrochloride (2-1000 nM; 72 hours) inhibits proliferation of multiple cancer cell lines, with mean EC50 values ranging from 8.4 to 46.9 nM, but not in nondividing normal cells[1].
TAK-960 dihydrochloride (8 nM) leads to G2/M cell cycle arrest without significant cytotoxicity in HeLa cells[2].
TAK-960 dihydrochloride exhibits (10 mg/kg; p.o.; once daily for 2 weeks) significant efficacy against multiple tumor xenografts[1].
In animal models, TAK-960 dihydrochloride (p.o.) increases pHH3 in a dose-dependent manner and significantly inhibits the growth of HT-29 colorectal cancer xenografts[1].
| Catalog Number | I046335 |
| Synonyms | 4-[(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-8H-pyrimido[4,5-b][1,4]diazepin-2-yl)amino]-2-fluoro-5-methoxy-N-(1-methylpiperidin-4-yl)benzamide;dihydrochloride |
| Molecular Formula | C27H36Cl2F3N7O3 |
| Purity | ≥95% |
| InChI | InChI=1S/C27H34F3N7O3.2ClH/c1-35-10-8-16(9-11-35)32-24(38)18-12-22(40-3)20(13-19(18)28)33-26-31-14-21-23(34-26)37(17-6-4-5-7-17)15-27(29,30)25(39)36(21)2;;/h12-14,16-17H,4-11,15H2,1-3H3,(H,32,38)(H,31,33,34);2*1H |
| InChIKey | CEMOEYRTQUGSJV-UHFFFAOYSA-N |
| SMILES | CN1CCC(CC1)NC(=O)C2=CC(=C(C=C2F)NC3=NC=C4C(=N3)N(CC(C(=O)N4C)(F)F)C5CCCC5)OC.Cl.Cl |
| Reference | [1]. Hikichi Y, et al. TAK-960, a novel, orally available, selective inhibitor of polo-like kinase 1, shows broad-spectrum preclinical antitumor activity in multiple dosing regimens. Mol Cancer Ther. 2012 Mar;11(3):700-9. [2]. Inoue M, et al. PLK1 blockade enhances therapeutic effects of radiation by inducing cell cycle arrest at the mitotic phase. Sci Rep. 2015 Oct 27;5:15666. |
