TAK-960 HCl is a potent, orally bioavailable, selective polo-like kinase 1 (PLK1) inhibitor (antagonist) with IC50 of 0.8 nM. TAK-960 HCl also inhibits PLK2 and PLK3 with IC50 of 16.9 and 50.2 nM respectively. TAK-960 HCl suppresses the proliferation/growth of various tumor cell lines and has significant efficacy in various tumor xenografts.

Physicochemical Properties

Molecular Formula	C27H34F3N7O3.CLH
Molecular Weight	598.060115098953
Exact Mass	597.244
CAS #	1137868-96-2
Related CAS #	TAK-960;1137868-52-0;TAK-960 dihydrochloride;TAK-960 monohydrochloride;2108449-45-0
PubChem CID	91826087
Appearance	Typically exists as solid at room temperature
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	6
Heavy Atom Count	41
Complexity	903
Defined Atom Stereocenter Count	0
SMILES	O=C(NC1CCN(C)CC1)C2=CC(OC)=C(NC3=NC=C(N4C)C(N(C5CCCC5)CC(F)(F)C4=O)=N3)C=C2F.[H]Cl.[F,Cl,Br,I]
InChi Key	QZBHDFGFNVMONB-UHFFFAOYSA-N
InChi Code	InChI=1S/C27H34F3N7O3.ClH/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);1H
Chemical Name	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;hydrochloride
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	PLK1 0.8 nM (IC50) PLK2 16.9 nM (IC50) PLK3 50.2 nM (IC50) FAK/PTK2 19.6 nM (IC50) MLCK/MYLK 25.6 nM (IC50) FES/FPS 58.2 nM (IC50)
ln Vitro	Treatment with TAK-960 hydrochloride results in an accumulation of G2-M cells, abnormal polo mitotic morphology, and elevated histone H3 phosphorylation (pHH3). With mean EC50 values ranging from 8.4 to 46.9 nM, TAK-960 hydrochloride (2-1000 nM; 72 hours) inhibits the growth of several cancer cell lines, but not nondividing normal cells[1]. In HeLa cells, TAK-960 hydrochloride (8 nM) causes G2/M cell cycle arrest without appreciable cytotoxicity[2].
ln Vivo	TAK-960 hydrochloride shows notable activity against various tumor xenografts (10 mg/kg; po; once daily for 2 weeks)[1]. TAK-960 hydrochloride (po) strongly suppresses the growth of HT-29 colorectal cancer xenografts in animal models and elevates pHH3 in a dose-dependent manner[1].
Cell Assay	Cell Viability Assay[1] Cell Types: HT-29, HCT116, COLO320DM, HCT-15, RKO, SW480, K-562…. Hela, DU 145 cells Tested Concentrations: 2-1000 nM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibited proliferation of human cancer cell lines regardless of TP53 and KRAS mutation and MDR1 expression status.
Animal Protocol	Animal/Disease Models: nude mice or SCID (severe combined immunodeficient) mouse (bearing HCT116, PC-3, BT474, A549 , NCI-H1299, NCI-H1975, A2780, and MV4-11 cells)[1] Doses: 10 mg/kg Route of Administration: Po; one time/day for 2 weeks Experimental Results: Substantial antitumor activity and good tolerability.
References	[1]. 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]. PLK1 blockade enhances therapeutic effects of radiation by inducing cell cycle arrest at the mitotic phase. Sci Rep. 2015 Oct 27;5:15666.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.6721 mL	8.3604 mL	16.7207 mL
	5 mM	0.3344 mL	1.6721 mL	3.3441 mL
	10 mM	0.1672 mL	0.8360 mL	1.6721 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.