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TAK-960 PLK inhibitor

Cat.No.S1239

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).
TAK-960 PLK inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 561.6

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Quality Control

Batch: S123901 DMSO]13 mg/mL]false]Ethanol]3 mg/mL]false]Water]Insoluble]false Purity: 99.92%
99.92

Solubility

In vitro
Batch:

DMSO : 13 mg/mL (23.14 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 3 mg/mL

Water : Insoluble

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In vivo
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Chemical Information, Storage & Stability

Molecular Weight 561.6 Formula

C27H34F3N7O3

 Storage (From the date of receipt)
CAS No. 1137868-52-0 Download SDF Storage of Stock Solutions

Mechanism of Action

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.
Targets/IC50/Ki
PLK1
In vitro

TAK-960 has shown activity in several tumor cell lines including those that express multidrug resistant protein 1 (MDR1). Consistent with PLK1 inhibition, this compound treatment gives rise to accumulation of G2/M cells, aberrant "polo" mitosis morphology, and increases 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 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 this chemical in the cell lines tested.

Kinase Assay
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 this compound inhibition (1 μM) using HotSpotSM technology and IC50 values for the selected kinases are determined.
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. Treatment with once-daily this compound exhibits significant efficacy against multiple tumor xenografts, including an Doxorubicin-resistant xenograft model and a disseminated leukemia model.

References

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01179399 Terminated
Advanced Nonhematological Malignancies
Millennium Pharmaceuticals Inc.
 September 2010 Phase 1

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