TAK-960

Cas：1137868-52-0 (free base)

Product Information：

TAK-960 is a n orally available PLK1 inhibitor with potential antineoplastic activity. Polo-like kinase 1 inhibitor TAK-960 selectively inhibits PLK1, inducing selective G2/M cell-cycle arrest followed by apoptosis in a variety of tumor cells while causing reversible cell-cycle arrest at the G1 and G2 stages without apoptosis in normal cells. PLK1 inhibition may result in the inhibition of proliferation in PLK1-overexpressed tumor cells. PLK1, named after the polo gene of Drosophila melanogaster, is a serine/threonine kinase crucial in the regulation of mitosis.

Chemical Formula: C27H34F3N7O3

Exact Mass: 561.26752

Molecular Weight: 561.59917

Elemental Analysis: C, 57.74; H, 6.10; F, 10.15; N, 17.46; O, 8.55

Synonym: 

TAK960

TAK 960

TAK960

Chemical Name:

4-((9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-yl)amino)-2-fluoro-5-methoxy-N-(1-methylpiperidin-4-yl)benzamide

InChi Key:

GWRSATNRNFYMDI-UHFFFAOYSA-N

InChi Code: InChI=1S/C27H34F3N7O3/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)

Smiles Code:

O=C(NC1CCN(C)CC1)C2=CC(OC)=C(NC3=NC=C(N4C)C(N(C5CCCC5)CC(F)(F)C4=O)=N3)C=C2F

Technical Data：

Appearance: White to beige 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

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

In Vitro：

TAK-960 treatment causes accumulation of G2-M cells, aberrant polo mitosis morphology, and increased phosphorylation of histone H3 (pHH3). TAK-960 (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.

TAK-960 (8 nM) leads to G2/M cell cycle arrest without significant cytotoxicity in HeLa cells.

In Vivo：

TAK-960 exhibits (10 mg/kg; p.o.; once daily for 2 weeks) significant efficacy against multiple tumor xenografts.

In animal models, TAK-960 (p.o.) increases pHH3 in a dose-dependent manner and significantly inhibits the growth of HT-29 colorectal cancer xenografts.

References：

1. Hennenberg M, Kuppermann P, Yu Q, Herlemann A, Tamalunas A, Wang Y, Rutz B, Ciotkowska A, Strittmatter F, Stief CG, Gratzke C. Inhibition of Prostate Smooth Muscle Contraction by Inhibitors of Polo-Like Kinases. Front Physiol. 2018 Jun 15;9:734. doi: 10.3389/fphys.2018.00734. PMID: 29962965; PMCID: PMC6013909.

2. Klauck PJ, Bagby SM, Capasso A, Bradshaw-Pierce EL, Selby HM, Spreafico A, Tentler JJ, Tan AC, Kim J, Arcaroli JJ, Purkey A, Messersmith WA, Kuida K, Eckhardt SG, Pitts TM. Antitumor activity of the polo-like kinase inhibitor, TAK-960, against preclinical models of colorectal cancer. BMC Cancer. 2018 Feb 5;18(1):136. doi: 10.1186/s12885-018-4036-z. PMID: 29402316; PMCID: PMC5800287.

3. Talati C, Griffiths EA, Wetzler M, Wang ES. Polo-like kinase inhibitors in hematologic malignancies. Crit Rev Oncol Hematol. 2016 Feb;98:200-10. doi: 10.1016/j.critrevonc.2015.10.013. Epub 2015 Nov 4. PMID: 26597019.

4. Inoue M, Yoshimura M, Kobayashi M, Morinibu A, Itasaka S, Hiraoka M, Harada H. PLK1 blockade enhances therapeutic effects of radiation by inducing cell cycle arrest at the mitotic phase. Sci Rep. 2015 Oct 27;5:15666. doi: 10.1038/srep15666. PMID: 26503893; PMCID: PMC4621528.

5. Nair JS, Schwartz GK. Inhibition of polo like kinase 1 in sarcomas induces apoptosis that is dependent on Mcl-1 suppression. Cell Cycle. 2015;14(19):3101-11. doi: 10.1080/15384101.2015.1078033. PMID: 26236920; PMCID: PMC4825583.

Products are for research use only. Not for human use.