6AYD

Pim1 complexed with N-(6-(4-hydroxyphenyl)-1H-indazol-3-yl)cyclopropanecarboxamide

Summary for 6AYD

• Entry DOI: 10.2210/pdb6ayd/pdb
• Descriptor: Serine/threonine-protein kinase pim-1, N-[6-(4-hydroxyphenyl)-2H-indazol-3-yl]cyclopropanecarboxamide (3 entities in total)
• Functional Keywords: kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Isoform 2: Cytoplasm. Isoform 1: Cell membrane: P11309
• Total number of polymer chains: 1
• Total formula weight: 38355.47

Authors

Shewchuk, L.M.,Henley, Z.A. (deposition date: 2017-09-08, release date: 2017-12-27, Last modification date: 2023-10-04)

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 Å)