Uses
TAK-960 is a potent and selective inhibitor of polo-like kinase 1 (PLK1), a serine/threonine protein kinase involved in key processes during mitosis. TAK-960 has shown activity in several tumor cell lines, including those that express multidrug-resistant protein 1 (MDR1). TAK-960 treatments has shown significant efficacy against multiple tumor xenografts and is a potential chemotherapeutic agent for patients with advanced tumors.
Biological Activity
polo-like kinase 1 (plk1) is a serine/threonine protein kinase involved in key mitosis processes. human plk1 has been shown to be overexpressed in various human cancers. elevated levels of plk1 have been associated with poor prognosis, making it an attractive target for anticancer therapy. tak-960 is a novel, investigational, orally bioavailable, potent, and selective plk1 inhibitor.
in vitro
tak-960 treatment caused accumulation of g2–m cells, aberrant polo mitosis morphology, and increased the phosphorylation of histone h3. tak-960 inhibited proliferation of multiple cancer cell lines, with mean ec50 ranging from 8.4 to 46.9 nmol/l, but not in nondividing normal cells [1].
in vivo
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. once daily treatment tak-960 exhibited significant efficacy against multiple tumor xenografts, including an adriamycin/paclitaxel-resistant xenograft model and a disseminated leukemia model [1].
IC 50
8.4 to 46.9 nmol/l for multiple cancer cell lines
References
[1] 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. 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.
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