2ghg

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[[Image:2ghg.gif|left|200px]]
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{{Seed}}
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[[Image:2ghg.png|left|200px]]
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{{STRUCTURE_2ghg| PDB=2ghg | SCENE= }}
{{STRUCTURE_2ghg| PDB=2ghg | SCENE= }}
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'''h-CHK1 complexed with A431994'''
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===h-CHK1 complexed with A431994===
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==Overview==
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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.
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The line below this paragraph, {{ABSTRACT_PUBMED_16644221}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 16644221 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16644221}}
==About this Structure==
==About this Structure==
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[[Category: Park, C.]]
[[Category: Park, C.]]
[[Category: Protein-inhibitor complex]]
[[Category: Protein-inhibitor complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:06:46 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 08:51:55 2008''

Revision as of 05:51, 28 July 2008

Image:2ghg.png

Template:STRUCTURE 2ghg

h-CHK1 complexed with A431994

Template:ABSTRACT PUBMED 16644221

About this Structure

2GHG is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Discovery and SAR of oxindole-pyridine-based protein kinase B/Akt inhibitors for treating cancers., Zhu GD, Gandhi VB, Gong J, Luo Y, Liu X, Shi Y, Guan R, Magnone SR, Klinghofer V, Johnson EF, Bouska J, Shoemaker A, Oleksijew A, Jarvis K, Park C, Jong RD, Oltersdorf T, Li Q, Rosenberg SH, Giranda VL, Bioorg Med Chem Lett. 2006 Jul 1;16(13):3424-9. Epub 2006 Apr 27. PMID:16644221

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