| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| 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)
The primary biological target of TAK-960 hydrochloride is polo-like kinase 1 (PLK1), a serine/threonine kinase that plays a critical role in mitosis, including centrosome maturation, spindle assembly, and cytokinesis. TAK-960 hydrochloride also inhibits PLK2 (IC50 = 16.9 nM) and PLK3 (IC50 = 50.2 nM), as well as FAK/PTK2 (IC50 = 19.6 nM), MLCK/MYLK (IC50 = 25.6 nM), and FES/FPS (IC50 = 58.2 nM). Its primary mechanism of action is the inhibition of PLK1, leading to G2/M cell cycle arrest and apoptosis in cancer cells. |
|---|---|
| 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].
In vitro, TAK-960 hydrochloride treatment causes accumulation of G2-M cells, aberrant polo mitosis morphology, and increased phosphorylation of histone H3 (pHH3). It 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 hydrochloride (8 nM) leads to G2/M cell cycle arrest without significant cytotoxicity in HeLa cells. It inhibits the proliferation of human cancer cell lines regardless of TP53 and KRAS mutation and MDR1 expression status. |
| 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].
In vivo, TAK-960 hydrochloride (10 mg/kg; p.o.; once daily for 2 weeks) exhibits significant efficacy against multiple tumor xenografts, including HCT116, PC-3, BT474, A549, NCI-H1299, NCI-H1975, A2780, and MV4-11. It increases pHH3 in a dose-dependent manner and significantly inhibits the growth of HT-29 colorectal cancer xenografts. These results demonstrate its potent in vivo antitumor activity. |
| Enzyme Assay |
The non-cellular enzyme or receptor binding assay for TAK-960 hydrochloride involves measuring its inhibition of PLK1 kinase activity. This is typically performed using a biochemical assay with purified recombinant PLK1 enzyme and a synthetic peptide substrate. The assay measures the phosphorylation of the peptide using a fluorescent or radioactive method. In the presence of the inhibitor, the rate of phosphorylation is reduced. The IC50 value is determined from the dose-response curve.
|
| 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. The in vitro cellular assay for TAK-960 hydrochloride involves treating cancer cell lines (HT-29, HCT116, COLO320DM, HCT-15, RKO, SW480, K-562, HeLa, DU 145) with various concentrations of the compound (2-1000 nM) for 72 hours. Cell viability is assessed using standard assays such as MTT or SRB to determine the IC50. Cell cycle analysis is performed using flow cytometry to detect G2/M arrest. The phosphorylation of histone H3 is assessed by western blotting or immunofluorescence. |
| 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. The in vivo animal experiment workflow for TAK-960 hydrochloride uses nude mice or SCID mice bearing human tumor xenografts (HCT116, PC-3, BT474, A549, NCI-H1299, NCI-H1975, A2780, MV4-11). The compound is administered orally at 10 mg/kg once daily for 2 weeks. Tumor growth is monitored by measuring tumor volume. The effect on pHH3 levels in tumor tissue is assessed by immunohistochemistry or western blotting. These studies are used to evaluate the in vivo efficacy of TAK-960 hydrochloride. |
| References |
|
| 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)
|
| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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