Reference Detail

Ref Type Journal Article
PMID (26279064)
Authors Scharow A, Raab M, Saxena K, Sreeramulu S, Kudlinzki D, Gande S, Dotsch C, Kurunci-Csacsko E, Klaeger S, Kuster B, Schwalbe H, Strebhardt K, Berg T
Title Optimized Plk1 PBD Inhibitors Based on Poloxin Induce Mitotic Arrest and Apoptosis in Tumor Cells.
Journal ACS chemical biology
Vol 10
Issue 11
Date 2015 Nov 20
URL
Abstract Text Polo-like kinase 1 (Plk1) is a central regulator of mitosis and has been validated as a target for antitumor therapy. The polo-box domain (PBD) of Plk1 regulates its kinase activity and mediates the subcellular localization of Plk1 and its interactions with a subset of its substrates. Functional inhibition of the Plk1 PBD by low-molecular weight inhibitors has been shown to represent a viable strategy by which to inhibit the enzyme, while avoiding selectivity issues caused by the conserved nature of the ATP binding site. Here, we report structure-activity relationships and mechanistic analysis for the first reported Plk1 PBD inhibitor, Poloxin. We present the identification of the optimized analog Poloxin-2, displaying significantly improved potency and selectivity over Poloxin. Poloxin-2 induces mitotic arrest and apoptosis in cultured human tumor cells at low micromolar concentrations, highlighting it as a valuable tool compound for exploring the function of the Plk1 PBD in living cells.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Poloxin-2 Poloxin-2 1 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
Poloxin-2 PLK1 Inhibitor 16 Poloxin-2, an analog of Poloxin, is a small molecule inhibitor of PLK1, which may result in apoptotic activity and induction of cell-cycle arrest (PMID: 26279064).
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 Advanced Solid Tumor not applicable Poloxin-2 Preclinical - Cell culture Actionable In a preclinical study, human cancer cells demonstrated sensitivity to treatment with Poloxin-2 in culture, resulting in cell-cycle arrest and apoptotic induction (PMID: 26279064). 26279064