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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. | ||||||||||||
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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. |
Molecular Profile | Treatment Approach |
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Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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Poloxin-2 | PLK1 Inhibitor 18 | 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). |
Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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