2f7x: Difference between revisions

Revision as of 18:18, 21 February 2008

Protein Kinase A bound to (S)-2-(1H-Indol-3-yl)-1-[5-((E)-2-pyridin-4-yl-vinyl)-pyridin-3-yloxymethyl]-ethylamine

OverviewOverview

A novel series of Akt/PKB inhibitors derived from a screening lead (1) has been prepared. The novel trans-3,4'-bispyridinylethylenes described herein are potent inhibitors of Akt/PKB with IC(50) values in the low double-digit nanomolar range against Akt1. Compound 2q shows excellent selectivity against distinct families of kinases such as tyrosine kinases and CAMK, and displays poor to modest selectivity against closely related kinases in the AGC and CMGC families. The cellular activities including inhibition of cell growth and phosphorylation of downstream target GSK3 are also described. The X-ray structure of compound 2q complexed with PKA in the ATP binding site was determined.

About this StructureAbout this Structure

2F7X is a Single protein structure of sequence from Bos taurus 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.

ReferenceReference

Discovery of trans-3,4'-bispyridinylethylenes as potent and novel inhibitors of protein kinase B (PKB/Akt) for the treatment of cancer: Synthesis and biological evaluation., Li Q, Li T, Zhu GD, Gong J, Claibone A, Dalton C, Luo Y, Johnson EF, Shi Y, Liu X, Klinghofer V, Bauch JL, Marsh KC, Bouska JJ, Arries S, De Jong R, Oltersdorf T, Stoll VS, Jakob CG, Rosenberg SH, Giranda VL, Bioorg Med Chem Lett. 2006 Mar 15;16(6):1679-85. Epub 2006 Jan 5. PMID:16403626

Page seeded by OCA on Thu Feb 21 17:18:35 2008

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

OCA

@@ Line 1: / Line 1: @@
-[[Image:2f7x.gif|left|200px]]<br /><applet load="2f7x" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:2f7x.gif|left|200px]]<br /><applet load="2f7x" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="2f7x, resolution 1.90&Aring;" />
 '''Protein Kinase A bound to (S)-2-(1H-Indol-3-yl)-1-[5-((E)-2-pyridin-4-yl-vinyl)-pyridin-3-yloxymethyl]-ethylamine'''<br />
 ==Overview==
-A novel series of Akt/PKB inhibitors derived from a screening lead (1) has, been prepared. The novel trans-3,4'-bispyridinylethylenes described herein, are potent inhibitors of Akt/PKB with IC(50) values in the low, double-digit nanomolar range against Akt1. Compound 2q shows excellent, selectivity against distinct families of kinases such as tyrosine kinases, and CAMK, and displays poor to modest selectivity against closely related, kinases in the AGC and CMGC families. The cellular activities including, inhibition of cell growth and phosphorylation of downstream target GSK3, are also described. The X-ray structure of compound 2q complexed with PKA, in the ATP binding site was determined.
+A novel series of Akt/PKB inhibitors derived from a screening lead (1) has been prepared. The novel trans-3,4'-bispyridinylethylenes described herein are potent inhibitors of Akt/PKB with IC(50) values in the low double-digit nanomolar range against Akt1. Compound 2q shows excellent selectivity against distinct families of kinases such as tyrosine kinases and CAMK, and displays poor to modest selectivity against closely related kinases in the AGC and CMGC families. The cellular activities including inhibition of cell growth and phosphorylation of downstream target GSK3 are also described. The X-ray structure of compound 2q complexed with PKA in the ATP binding site was determined.
 ==About this Structure==
-F7X is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with 4EA 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2F7X OCA].
+F7X is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=4EA:'>4EA</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=2F7X OCA].
 ==Reference==
@@ Line 15: / Line 15: @@
 [[Category: Single protein]]
 [[Category: Arries, S.]]
-[[Category: Bauch, J.L.]]
+[[Category: Bauch, J L.]]
-[[Category: Bouska, J.J.]]
+[[Category: Bouska, J J.]]
 [[Category: Claibone, A.]]
 [[Category: Dalton, C.]]
-[[Category: Giranda, V.L.]]
+[[Category: Giranda, V L.]]
 [[Category: Gong, J.]]
-[[Category: Jakob, C.G.]]
+[[Category: Jakob, C G.]]
-[[Category: Johnson, E.F.]]
+[[Category: Johnson, E F.]]
-[[Category: Jong, R.De.]]
+[[Category: Jong, R De.]]
 [[Category: Klinghofer, V.]]
 [[Category: Li, Q.]]
@@ Line 29: / Line 29: @@
 [[Category: Liu, X.]]
 [[Category: Luo, Y.]]
-[[Category: Marsh, K.C.]]
+[[Category: Marsh, K C.]]
 [[Category: Oltersdorf, T.]]
-[[Category: Rosenberg, S.H.]]
+[[Category: Rosenberg, S H.]]
 [[Category: Shi, Y.]]
-[[Category: Stoll, V.S.]]
+[[Category: Stoll, V S.]]
-[[Category: Zhu, G.D.]]
+[[Category: Zhu, G D.]]
 [[Category: 4EA]]
 [[Category: akt inhibitors]]
 [[Category: protein kinase a]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 10:25:05 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:18:35 2008''