2ghg: Difference between revisions
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New page: left|200px<br /> <applet load="2ghg" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ghg, resolution 3.50Å" /> '''h-CHK1 complexed wi... |
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[[Image:2ghg.gif|left|200px]]<br /> | [[Image:2ghg.gif|left|200px]]<br /><applet load="2ghg" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2ghg" size=" | |||
caption="2ghg, resolution 3.50Å" /> | caption="2ghg, resolution 3.50Å" /> | ||
'''h-CHK1 complexed with A431994'''<br /> | '''h-CHK1 complexed with A431994'''<br /> | ||
==Overview== | ==Overview== | ||
We describe a series of potent and selective oxindole-pyridine-based | 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. | ||
==About this Structure== | ==About this Structure== | ||
2GHG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with A53 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http:// | 2GHG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=A53:'>A53</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GHG OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: protein-inhibitor complex]] | [[Category: protein-inhibitor complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:31:42 2008'' | ||
