Reference Detail

Ref Type Journal Article
PMID (22188812)
Authors Hikichi Y, Honda K, Hikami K, Miyashita H, Kaieda I, Murai S, Uchiyama N, Hasegawa M, Kawamoto T, Sato T, Ichikawa T, Cao S, Nie Z, Zhang L, Yang J, Kuida K, Kupperman E
Title TAK-960, a novel, orally available, selective inhibitor of polo-like kinase 1, shows broad-spectrum preclinical antitumor activity in multiple dosing regimens.
Journal Molecular cancer therapeutics
Vol 11
Issue 3
Date 2012 Mar
URL
Abstract Text Polo-like kinase 1 (PLK1) is a serine/threonine protein kinase involved in key processes during mitosis. Human PLK1 has been shown to be overexpressed in various human cancers, and elevated levels of PLK1 have been associated with poor prognosis, making it an attractive target for anticancer therapy. TAK-960 [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] 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). Consistent with PLK1 inhibition, TAK-960 treatment caused accumulation of G(2)-M cells, aberrant polo mitosis morphology, and increased phosphorylation of histone H3 (pHH3) in vitro and in vivo. TAK-960 inhibited proliferation of multiple cancer cell lines, with mean EC(50) values ranging from 8.4 to 46.9 nmol/L, but not in nondividing normal cells (EC(50) >1,000 nmol/L). The mutation status of TP53 or KRAS and MDR1 expression did not correlate with the potency of TAK-960 in the cell lines tested. In animal models, oral administration of TAK-960 increased pHH3 in a dose-dependent manner and significantly inhibited the growth of HT-29 colorectal cancer xenografts. Treatment with once daily TAK-960 exhibited significant efficacy against multiple tumor xenografts, including an adriamycin/paclitaxel-resistant xenograft model and a disseminated leukemia model. TAK-960 has entered clinical evaluation in patients with advanced cancers.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
TAK-960 TAK-960 6 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
TAK-960 PLK1 Inhibitor 16 TAK-960 is an inhibitor of PLK1, which may result in cell growth inhibition and a reduction in tumor size (PMID: 22188812).
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown breast cancer not applicable TAK-960 Preclinical - Cell line xenograft Actionable In a preclinical study, breast cancer cells treated with TAK-960 demonstrated a decrease in tumor size in cell line xenograft models (PMID: 22188812). 22188812
Unknown unknown lung cancer not applicable TAK-960 Preclinical - Cell line xenograft Actionable In a preclinical study, lung cancer cells treated with TAK-960 demonstrated a decrease in tumor size in cell line xenograft models (PMID: 22188812). 22188812
Unknown unknown leukemia not applicable TAK-960 Preclinical - Cell line xenograft Actionable In a preclinical study, colorectal cancer cells treated with TAK-960 demonstrated cell growth inhibition, decreased tumor size, and increased median survival in both culture and cell line xenograft models (PMID: 22188812). 22188812
Unknown unknown ovarian cancer not applicable TAK-960 Preclinical - Cell line xenograft Actionable In a preclinical study, ovarian cancer cells treated with TAK-960 demonstrated cell growth inhibition and decreased tumor size in both culture and cell line xenograft models (PMID: 22188812). 22188812
Unknown unknown prostate cancer not applicable TAK-960 Preclinical - Cell line xenograft Actionable In a preclinical study, prostate cancer cells treated with TAK-960 demonstrated a decrease in tumor size in cell line xenograft models (PMID: 22188812). 22188812
Unknown unknown colorectal cancer not applicable TAK-960 Preclinical - Cell line xenograft Actionable In a preclinical study, colorectal cancer cells treated with TAK-960 demonstrated cell growth inhibition and decreased tumor size in both culture and cell line xenograft models (PMID: 22188812). 22188812