The Design, Synthesis and Potential Utility of Fluorescence Probes that Target DFG-out Conformation of p38[alpha] for High Throughput Screening Binding Assay

Journal Article · Mon Oct 18 00:00:00 EDT 2010 · Chem. Biol. Drug Des.

DOI:https://doi.org/10.1111/j.1747-0285.2009.00884.x· OSTI ID:1006146

Tecle, Haile; Feru, Frederic; Liu, Hu; Kuhn, Cyrille; Rennie, Glen; Morris, Mark; Shao, Jiangxing; Cheng, Alan C; Gikunju, Diana; Miret, Juan; Coli, Rocco; Xi, Simon ^[1]; Clugston, Susan L; Low, Simon; Kazmirski, Steven; Ding, Yuan-Hua; Cao, Qing; Johnson, Theresa L; Deshmukh, Gayatri D; DiNitto, Jonathan P ; Wu, Joe C; English, Jessie M; Pfizer,

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1. Hualin

The design, synthesis and utility of fluorescence probes that bind to the DFG-out conformation of p38{alpha} kinase are described. Probes that demonstrate good affinity for p38{alpha}, have been identified and one of the probes, PF-04438255, has been successfully used in an high throughput screening (HTS) assay to identify two novel non-classical p38{alpha} inhibitors. In addition, a cascade activity assay was utilized to validate the selective binding of these non-classical kinase inhibitors to the unactive form of the enzyme.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States)
• Sponsoring Organization: USDOE
• OSTI ID: 1006146
• Journal Information: Chem. Biol. Drug Des., Vol. 74, Issue (6) ; 12, 2009; ISSN 1747-0227
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE
AFFINITY
DESIGN
FLUORESCENCE
PHOSPHOTRANSFERASES
PROBES
SYNTHESIS
TARGETS