2pe2 | pdb_00002pe2
CRYSTAL STRUCTURE OF HUMAN PHOSPHOINOSITIDE-DEPENDENT PROTEIN KINASE 1 (PDK1) 3-{5-[2-Oxo-5-ureido-1,2-dihydro-indol-(3Z)-ylidenemethyl]-1H-pyrrol-3-yl}-N-(2-piperidin-1-yl-ethyl)-benzamide COMPLEX
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| 2pe2, resolution 2.13Å | |||||||||||||
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| Ligands: | SO4, 464 and GOL | ||||||||||||
| Gene: | PDPK1, PDK1 (Homo sapiens) | ||||||||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Overview
Based on the lead compound BX-517, a series of C-4' substituted indolinones have been synthesized and evaluated for PDK1 inhibition. Modification at C-4' of the pyrrole afforded potent compounds (7b and 7d) with improved solubility and ADME properties. In this letter, we describe the synthesis, selectivity profile, and pharmacokinetic data of selected compounds.
About this Structure
2PE2 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: optimization of BX-517., Islam I, Brown G, Bryant J, Hrvatin P, Kochanny MJ, Phillips GB, Yuan S, Adler M, Whitlow M, Lentz D, Polokoff MA, Wu J, Shen J, Walters J, Ho E, Subramanyam B, Zhu D, Feldman RI, Arnaiz DO, Bioorg Med Chem Lett. 2007 Jul 15;17(14):3819-25. Epub 2007 May 23. PMID:17544272
Page seeded by OCA on Thu Mar 20 18:11:53 2008
