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1wbv
From Proteopedia
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IDENTIFICATION OF NOVEL P38 ALPHA MAP KINASE INHIBITORS USING FRAGMENT-BASED LEAD GENERATION.
Overview
We describe the structure-guided optimization of the molecular fragments, 2-amino-3-benzyloxypyridine 1 (IC(50) 1.3 mM) and, 3-(2-(4-pyridyl)ethyl)indole 2 (IC(50) 35 microM) identified using X-ray, crystallographic screening of p38alpha MAP kinase. Using two separate case, studies, the article focuses on the key compounds synthesized, the, structure-activity relationships and the binding mode observations made, during this optimization process, resulting in two potent lead series that, demonstrate significant increases in activity. We describe the process of, compound elaboration either through the growing out from fragments into, adjacent pockets or through the conjoining of overlapping fragments and, demonstrate that we have exploited the mobile conserved activation loop, consisting in ... [(full description)]
About this Structure
1WBV is a [Single protein] structure of sequence from [Homo sapiens] with LI3, DMS and GOL as [ligands]. Active as [[1]], with EC number [2.7.1.37]. Full crystallographic information is available from [OCA].
Reference
Identification of novel p38alpha MAP kinase inhibitors using fragment-based lead generation., Gill AL, Frederickson M, Cleasby A, Woodhead SJ, Carr MG, Woodhead AJ, Walker MT, Congreve MS, Devine LA, Tisi D, O'Reilly M, Seavers LC, Davis DJ, Curry J, Anthony R, Padova A, Murray CW, Carr RA, Jhoti H, J Med Chem. 2005 Jan 27;48(2):414-26. PMID:15658855
Page seeded by OCA on Mon Oct 29 18:58:27 2007
