Identification of benzofuran-4,5-diones as novel and selective non-hydroxamic acid, non-peptidomimetic based inhibitors of human peptide deformylase.

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Antczak C, Shum D, Bassit B, Frattini MG, Li Y, de Stanchina E, Scheinberg DA, Djaballah H

Identification of benzofuran-4,5-diones as novel and selective non-hydroxamic acid, non-peptidomimetic based inhibitors of human peptide deformylase.

Bioorg Med Chem Lett. 2011 Aug 1;21(15):4528-32. doi: 10.1016/j.bmcl.2011.05.129. Epub 2011 Jun 12.

PubMed ID

21719286 [ View in PubMed

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Abstract

Selective inhibitors of human peptide deformylase (HsPDF) are predicted to constitute a new class of antitumor agents. We report the identification of benzofuran-4,5-diones as the first known selective HsPDF inhibitors and we describe their selectivity profile in a panel of metalloproteases. We characterize their structure-activity relationships for antitumor activity in a panel of cancer cell lines, and we assess their in vivo efficacy in a mouse xenograft model. Our results demonstrate that selective HsPDF inhibitors based on the benzofuran-4,5-dione scaffold constitute a novel class of antitumor agents that are potent in vitro and in vivo.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
2-[(Formyl-Hydroxy-Amino)-Methyl]-Heptanoic Acid [1-(2-Hydroxymethyl-Pyrrolidine-1-Carbonyl)-2-Methyl-Propyl]-Amide	Peptide deformylase, mitochondrial	IC 50 (nM)	2700	N/A	N/A	Details