2PE2

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

Summary for 2PE2

• Entry DOI: 10.2210/pdb2pe2/pdb
• Related: 1H1W 1OKY 1OKZ 1UU3 1UU7 1UU8 1UU9 1UVR 1Z5M 2PE0 2PE1
• Descriptor: 3-phosphoinositide-dependent protein kinase 1, SULFATE ION, 3-[5-({5-[(AMINOCARBONYL)AMINO]-2-OXO-2H-INDOL-3-YL}METHYL)-1H-PYRROL-3-YL]-N-(2-PIPERIDIN-1-YLETHYL)BENZAMIDE, ... (5 entities in total)
• Functional Keywords: protein inhibitor complex, serine kinase, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: O15530
• Total number of polymer chains: 1
• Total formula weight: 34653.63

Authors

Whitlow, M.,Adler, M. (deposition date: 2007-04-01, release date: 2007-06-19, Last modification date: 2011-07-13)

Primary citation

Islam, I.,Brown, G.,Bryant, J.,Hrvatin, P.,Kochanny, M.J.,Phillips, G.B.,Yuan, S.,Adler, M.,Whitlow, M.,Lentz, D.,Polokoff, M.A.,Wu, J.,Shen, J.,Walters, J.,Ho, E.,Subramanyam, B.,Zhu, D.,Feldman, R.I.,Arnaiz, D.O.
Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: Optimization of BX-517.
Bioorg.Med.Chem.Lett., 17:3819-3825, 2007

PubMed Abstract: 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.

PubMed: 17544272
DOI: 10.1016/j.bmcl.2007.05.060

Experimental method

X-RAY DIFFRACTION (2.13 Å)