2ghg
From Proteopedia
(New page: 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'' |
Revision as of 15:31, 21 February 2008
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h-CHK1 complexed with A431994
Overview
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
2GHG is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 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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