2f7e: Difference between revisions
No edit summary |
No edit summary |
||
| Line 5: | Line 5: | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=2EA:(1S)-2-(1H-INDOL-3-YL)-1-{[(5-ISOQUINOLIN-6-YLPYRIDIN-3-YL)OXY]METHYL}ETHYLAMINE'>2EA</scene> | |LIGAND= <scene name='pdbligand=2EA:(1S)-2-(1H-INDOL-3-YL)-1-{[(5-ISOQUINOLIN-6-YLPYRIDIN-3-YL)OXY]METHYL}ETHYLAMINE'>2EA</scene> | ||
|ACTIVITY= [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] | |ACTIVITY= <span class='plainlinks'>[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] </span> | ||
|GENE= PRKACA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 Bos taurus]) | |GENE= PRKACA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 Bos taurus]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1ydr|1YDR]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2f7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f7e OCA], [http://www.ebi.ac.uk/pdbsum/2f7e PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2f7e RCSB]</span> | |||
}} | }} | ||
| Line 24: | Line 27: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Stoll, V S.]] | [[Category: Stoll, V S.]] | ||
[[Category: akt inhibitor]] | [[Category: akt inhibitor]] | ||
[[Category: protein kinase some]] | [[Category: protein kinase some]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:58:57 2008'' | ||
Revision as of 02:58, 31 March 2008
| |||||||
| , resolution 2.00Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | PRKACA (Bos taurus) | ||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Related: | 1YDR
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
PKA complexed with (S)-2-(1H-Indol-3-yl)-1-(5-isoquinolin-6-yl-pyridin-3-yloxymethyl-etylamine
OverviewOverview
Structure-based design and synthesis of the 3,4'-bispyridinylethylene series led to the discovery of 3-isoquinolinylpyridine 13a as a potent PKB/Akt inhibitor with an IC(50) of 1.3nM against Akt1. Compound 13a shows excellent selectivity against distinct families of kinases such as tyrosine kinases and CAMK, and displays poor to marginal selectivity against closely related kinases in the AGC and CMGC families. Moreover, 13a demonstrates potent cellular activity comparable to staurosporine, with IC(50) values of 0.42 and 0.59microM against MiaPaCa-2 and the Akt1 overexpressing FL5.12-Akt1, respectively. Inhibition of phosphorylation of the Akt downstream target GSK3 was also observed in FL5.12-Akt1 cells with an EC(50) of 1.5microM. The X-ray structures of 12 and 13a in complex with PKA in the ATP-binding site were determined.
About this StructureAbout this Structure
2F7E is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.
ReferenceReference
Synthesis and structure-activity relationship of 3,4'-bispyridinylethylenes: discovery of a potent 3-isoquinolinylpyridine inhibitor of protein kinase B (PKB/Akt) for the treatment of cancer., Li Q, Woods KW, Thomas S, Zhu GD, Packard G, Fisher J, Li T, Gong J, Dinges J, Song X, Abrams J, Luo Y, Johnson EF, Shi Y, Liu X, Klinghofer V, Des Jong R, Oltersdorf T, Stoll VS, Jakob CG, Rosenberg SH, Giranda VL, Bioorg Med Chem Lett. 2006 Apr 1;16(7):2000-7. Epub 2006 Jan 18. PMID:16413780
Page seeded by OCA on Mon Mar 31 02:58:57 2008