Identification and structure-activity relationships of substituted pyridones as inhibitors of Pim-1 kinase.

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Cheney IW, Yan S, Appleby T, Walker H, Vo T, Yao N, Hamatake R, Hong Z, Wu JZ

Identification and structure-activity relationships of substituted pyridones as inhibitors of Pim-1 kinase.

Bioorg Med Chem Lett. 2007 Mar 15;17(6):1679-83. Epub 2007 Jan 4.

PubMed ID

17251021 [ View in PubMed

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Abstract

A novel series of highly potent substituted pyridone Pim-1 kinase inhibitors is described. Structural requirements for in vitro activity are outlined as well as a complex crystal structure with the most potent Pim-1 inhibitor reported (IC(50)=50 nM). A hydrogen bond matrix involving the Pim-1 inhibitor, two water molecules, and the catalytic core, together with a potential weak hydrogen bond between an aromatic hydrogen on the R(1) phenyl ring and a main-chain carbonyl of Pim-1, accounts for the overall potency of this inhibitor.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
6-(5-BROMO-2-HYDROXYPHENYL)-2-OXO-4-PHENYL-1,2-DIHYDROPYRIDINE-3-CARBONITRILE	Serine/threonine-protein kinase pim-1	IC 50 (nM)	50	7.5	23	Details