TAK-960

Catalog No.S1239 Batch:S123901

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Technical Data

Formula

C27H34F3N7O3
Molecular Weight 561.6 CAS No. 1137868-52-0
Solubility (25°C)* In vitro DMSO 13 mg/mL (23.14 mM)
Ethanol 3 mg/mL (5.34 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description TAK-960 is a novel, investigational, orally bioavailable, potent, and selective PLK1 inhibitor that has shown activity in several tumor cell lines, including those that express multidrug-resistant protein 1 (MDR1).
Targets
PLK1 [1]
In vitro

TAK-960 has shown activity in several tumor cell lines including those that express multidrug resistant protein 1 (MDR1). [1] Consistent with PLK1 inhibition, TAK-960 treatment gives rise to accumulation of G2/M cells, aberrant "polo" mitosis morphology, and increases phosphorylation of histone H3 (pHH3). [1] TAK-960 inhibits proliferation of multiple cancer cell lines, with mean EC50 values ranging from 8.4 to 46.9 nM, but not in non-dividing normal cells (EC50 >1,000 nM). The mutation status of TP53 or KRAS and MDR1 expression does not correlate with the potency of TAK-960 in the cell lines tested. [1]
In vivo

In animal models, oral administration of TAK-960 increases pHH3 in a dose-dependent manner and significantly inhibits the growth of HT-29 colorectal cancer xenografts. [1] Treatment with once-daily TAK-960 exhibits significant efficacy against multiple tumor xenografts, including an Doxorubicin/Paclitaxel-resistant xenograft model and a disseminated leukemia model. [1]
Features The discovery of TAK -960 provides an interesting example of how the addition of fluorine atoms during optimization significantly alters the attributes of the leads series.

Protocol (from reference)

Kinase Assay:

[1]
  • Biochemical kinase inhibition assays

    The inhibitory activity of TAK-960 is assessed by the TR-FRET assay, which measures the ATP-dependent phosphorylation of a biotinylated substrate peptide corresponding to residues 2470 through 2488 of the mammalian target of rapamycin protein (Biotin-AGAGTVPESIHSFIGDGLV). A total of 288 kinases are screened for TAK-960 inhibition (1 μM) using HotSpotSM technology and IC50 values for the selected kinases are determined.
Cell Assay:

[1]
  • Cell lines

    Human tumor cell lines including those with TP53 or KRAS mutations or MDR1 overexpression

  • Concentrations

    0.001-1μM

  • Incubation Time

    72 hours

  • Method

    Cells are seeded into 96-well plates at 3-30 × 103 cells/well in appropriate medium plus 10% fetal calf serum (FCS). After 24 hours, cells are treated with serial dilutions of TAK-960, and 72 hours later, the number of viable cells is assessed using the CellTiter-Glo Assay. Calculation of EC50 values and statistical analysis are done.
Animal Study:

[1]
  • Animal Models

    Athymic nude mice (BALB/cAJc1-nu/nu), severe combined immunodeficiency (SCID) mice (C.B17-Icr- scid/scid Jcl) or NOD-scid mice (NOD.CB17-Prkdc scid/J)

  • Dosages

    30 mg/kg

  • Administration

    Oral dosing

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.