2GHG

h-CHK1 complexed with A431994

Summary for 2GHG

• Entry DOI: 10.2210/pdb2ghg/pdb
• Related: 2AYP 2FGA
• Descriptor: Serine/threonine-protein kinase Chk1, 5-{5-[(S)-2-AMINO-3-(1H-INDOL-3-YL)-PROPOXYL]-PYRIDIN-3-YL}-3-[1-(1H-PYRROL-2-YL)-METH-(Z)-YLIDENE]-1,3-DIHYDRO-INDOL-2-ONE (3 entities in total)
• Functional Keywords: protein-inhibitor complex, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: O14757
• Total number of polymer chains: 1
• Total formula weight: 31544.28

Authors

Park, C. (deposition date: 2006-03-27, release date: 2007-03-27, Last modification date: 2024-02-14)

Primary citation

Zhu, G.D.,Gandhi, V.B.,Gong, J.,Luo, Y.,Liu, X.,Shi, Y.,Guan, R.,Magnone, S.R.,Klinghofer, V.,Johnson, E.F.,Bouska, J.,Shoemaker, A.,Oleksijew, A.,Jarvis, K.,Park, C.,De Jong, R.,Oltersdorf, T.,Li, Q.,Rosenberg, S.H.,Giranda, V.L.
Discovery and SAR of oxindole-pyridine-based protein kinase B/Akt inhibitors for treating cancers.
Bioorg.Med.Chem.Lett., 16:3424-3429, 2006

PubMed Abstract: We describe a series of potent and selective oxindole-pyridine-based protein kinase B/Akt inhibitors. The most potent compound 11n in this series demonstrated an IC(50) of 0.17nM against Akt1 and more than 100-fold selectivity over other Akt isozymes. The selectivity against other protein kinases was highly dependent on the C-3 substitutions at the oxindole scaffold, with unsubstituted 9e or 3-furan-2-ylmethylene (11n) more selective and 3-(1H-pyrrol-2-yl)methylene (11f) or 3-(1H-imidazol-2-yl)methylene (11k) less selective. In a mouse xenograft model, 9d, 11f, and 11n inhibited tumor growth but with accompanying toxicity.

PubMed: 16644221
DOI: 10.1016/j.bmcl.2006.04.005

Experimental method

X-RAY DIFFRACTION (3.5 Å)