5OY4

GSK3beta complex with N-(6-(3,4-dihydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)acetamide

Summary for 5OY4

• Entry DOI: 10.2210/pdb5oy4/pdb
• Descriptor: Glycogen synthase kinase-3 beta, Proto-oncogene FRAT1, SULFATE ION, ... (5 entities in total)
• Functional Keywords: phosphoinositide-3-kinase delta inhibitor, pi3k delta inhibitor, kinase cross-screening, transferase
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm : P49841 Q92837
• Total number of polymer chains: 4
• Total formula weight: 152975.12

Authors

Bax, B.D.,Convery, M.A. (deposition date: 2017-09-07, release date: 2017-11-01, Last modification date: 2024-11-20)

Primary citation

Henley, Z.A.,Bax, B.D.,Inglesby, L.M.,Champigny, A.,Gaines, S.,Faulder, P.,Le, J.,Thomas, D.A.,Washio, Y.,Baldwin, I.R.
From PIM1 to PI3K delta via GSK3 beta : Target Hopping through the Kinome.
ACS Med Chem Lett, 8:1093-1098, 2017

PubMed Abstract: Selective inhibitors of phosphoinositide 3-kinase delta are of interest for the treatment of inflammatory diseases. Initial optimization of a 3-substituted indazole hit compound targeting the kinase PIM1 focused on improving selectivity over GSK3β through consideration of differences in the ATP binding pockets. Continued kinase cross-screening showed PI3Kδ activity in a series of 4,6-disubstituted indazole compounds, and subsequent structure-activity relationship exploration led to the discovery of an indole-containing lead compound as a potent PI3Kδ inhibitor with selectivity over the other PI3K isoforms.

PubMed: 29057057
DOI: 10.1021/acsmedchemlett.7b00296

Experimental method

X-RAY DIFFRACTION (3.2 Å)