2o2u: Difference between revisions

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[[Image:2o2u.gif|left|200px]]<br />

[[Image:2o2u.gif|left|200px]]<br /><applet load="2o2u" size="350" color="white" frame="true" align="right" spinBox="true"

<applet load="2o2u" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="2o2u, resolution 2.450Å" />

'''Crystal structure of human JNK3 complexed with N-(3-cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)-2-fluorobenzamide'''<br />

==Overview==

The identification and exploration of a novel, potent and selective series, of N-(3-cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amide inhibitors of, JNK2 and JNK3 kinases is described. Compounds 5a and 11a were identified, as potent inhibitors of JNK3 (~~pIC(50)~~ 6.7 and 6.6, respectively), with, essentially equal potency against JNK2 (~~pIC(50)~~ 6.5). Selectivity within, the mitogen-activated protein kinase (MAPK) family, against JNK1, p38alpha, and ERK2, was observed for the series. X-ray crystallography of 5e and 8a, in JNK3 revealed a unique binding mode, with the 3-cyano substituent, forming an H-bond acceptor interaction with the hinge region of the, ATP-binding site.

The identification and exploration of a novel, potent and selective series of N-(3-cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amide inhibitors of JNK2 and JNK3 kinases is described. Compounds 5a and 11a were identified as potent inhibitors of JNK3 (pIC50 6.7 and 6.6, respectively), with essentially equal potency against JNK2 (pIC50 6.5). Selectivity within the mitogen-activated protein kinase (MAPK) family, against JNK1, p38alpha and ERK2, was observed for the series. X-ray crystallography of 5e and 8a in JNK3 revealed a unique binding mode, with the 3-cyano substituent forming an H-bond acceptor interaction with the hinge region of the ATP-binding site.

==Disease==

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==About this Structure==

2O2U 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 738 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=2O2U OCA].

2O2U 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=738:'>738</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O2U OCA].

==Reference==

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[[Category: kinase]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov 12 23~~:05:~~51 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:13:50 2008''

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@@ Line 1: / Line 1: @@
-[[Image:2o2u.gif|left|200px]]<br />
+[[Image:2o2u.gif|left|200px]]<br /><applet load="2o2u" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="2o2u" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="2o2u, resolution 2.450&Aring;" />
 '''Crystal structure of human JNK3 complexed with N-(3-cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)-2-fluorobenzamide'''<br />
 ==Overview==
-The identification and exploration of a novel, potent and selective series, of N-(3-cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amide inhibitors of, JNK2 and JNK3 kinases is described. Compounds 5a and 11a were identified, as potent inhibitors of JNK3 (pIC(50) 6.7 and 6.6, respectively), with, essentially equal potency against JNK2 (pIC(50) 6.5). Selectivity within, the mitogen-activated protein kinase (MAPK) family, against JNK1, p38alpha, and ERK2, was observed for the series. X-ray crystallography of 5e and 8a, in JNK3 revealed a unique binding mode, with the 3-cyano substituent, forming an H-bond acceptor interaction with the hinge region of the, ATP-binding site.
+The identification and exploration of a novel, potent and selective series of N-(3-cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amide inhibitors of JNK2 and JNK3 kinases is described. Compounds 5a and 11a were identified as potent inhibitors of JNK3 (pIC50 6.7 and 6.6, respectively), with essentially equal potency against JNK2 (pIC50 6.5). Selectivity within the mitogen-activated protein kinase (MAPK) family, against JNK1, p38alpha and ERK2, was observed for the series. X-ray crystallography of 5e and 8a in JNK3 revealed a unique binding mode, with the 3-cyano substituent forming an H-bond acceptor interaction with the hinge region of the ATP-binding site.
 ==Disease==
@@ Line 11: / Line 10: @@
 ==About this Structure==
-O2U 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 738 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2O2U OCA].
+O2U 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=738:'>738</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O2U OCA].
 ==Reference==
@@ Line 23: / Line 22: @@
 [[Category: kinase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 23:05:51 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:13:50 2008''