2f7e: Difference between revisions

Revision as of 03:33, 4 May 2008

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 Sun May 4 03:33:12 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:2f7e.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 2f7e |SIZE=350|CAPTION= <scene name='initialview01'>2f7e</scene>, resolution 2.00&Aring;
+The line below this paragraph, containing "STRUCTURE_2f7e", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=2EA:(1S)-2-(1H-INDOL-3-YL)-1-{[(5-ISOQUINOLIN-6-YLPYRIDIN-3-YL)OXY]METHYL}ETHYLAMINE'>2EA</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|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>
+or leave the SCENE parameter empty for the default display.
-|GENE= PRKACA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 Bos taurus])
+-->
-|DOMAIN=
+{{STRUCTURE_2f7e|  PDB=2f7e  |  SCENE=  }}
-|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>
-}}
 '''PKA complexed with (S)-2-(1H-Indol-3-yl)-1-(5-isoquinolin-6-yl-pyridin-3-yloxymethyl-etylamine'''
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 [[Category: Single protein]]
 [[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 Sun May  4 03:33:12 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:58:57 2008''