2rbe: Difference between revisions

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Revision as of 19:34, 20 March 2008

File:2rbe.jpg

, resolution 1.900Å

Ligands:

and

Gene:

HSD11B1, HSD11, HSD11L (Homo sapiens)

Activity:

11-beta-hydroxysteroid dehydrogenase, with EC number 1.1.1.146

Coordinates:

save as pdb, mmCIF, xml

The discovery of 2-anilinothiazolones as 11beta-HSD1 inhibitors

OverviewOverview

A series of 2-anilinothiazolones were prepared as inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). The most potent compounds contained a 2-chloro or 2-fluoro group on the aniline ring with an isopropyl substituent on the 5-position of the thiazolone ring (compounds 2 and 3, respectively). The binding mode was determined through the X-ray co-crystal structure of the enzyme with compound 3. This compound was also approximately 70-fold selective over 11beta-HSD2 and was orally bioavailable in rat pharmacokinetic studies. However, compound 3 was >580-fold less active in the 11beta-HSD1 cell assay when tested in the presence of 3% human serum albumin.

About this StructureAbout this Structure

2RBE is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

The discovery of 2-anilinothiazolones as 11beta-HSD1 inhibitors., Yuan C, St Jean DJ Jr, Liu Q, Cai L, Li A, Han N, Moniz G, Askew B, Hungate RW, Johansson L, Tedenborg L, Pyring D, Williams M, Hale C, Chen M, Cupples R, Zhang J, Jordan S, Bartberger MD, Sun Y, Emery M, Wang M, Fotsch C, Bioorg Med Chem Lett. 2007 Nov 15;17(22):6056-61. Epub 2007 Sep 25. PMID:17919905

Page seeded by OCA on Thu Mar 20 18:34:24 2008

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

OCA

@@ Line 1: / Line 1: @@
-[[Image:2rbe.jpg|left|200px]]<br /><applet load="2rbe" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:2rbe.jpg|left|200px]]
-caption="2rbe, resolution 1.900&Aring;" />
-'''The discovery of 2-anilinothiazolones as 11beta-HSD1 inhibitors'''<br />
+ {{Structure
+|PDB= 2rbe |SIZE=350|CAPTION= <scene name='initialview01'>2rbe</scene>, resolution 1.900&Aring;
+|SITE=
+|LIGAND= <scene name='pdbligand=ZMG:'>ZMG</scene> and <scene name='pdbligand=NDP:NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE'>NDP</scene>
+|ACTIVITY= [http://en.wikipedia.org/wiki/11-beta-hydroxysteroid_dehydrogenase 11-beta-hydroxysteroid dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.146 1.1.1.146]
+|GENE= HSD11B1, HSD11, HSD11L ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+}}
+'''The discovery of 2-anilinothiazolones as 11beta-HSD1 inhibitors'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-RBE 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=ZMG:'>ZMG</scene> and <scene name='pdbligand=NDP:'>NDP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/11-beta-hydroxysteroid_dehydrogenase 11-beta-hydroxysteroid dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.146 1.1.1.146] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RBE OCA].
+RBE is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RBE OCA].
 ==Reference==
-The discovery of 2-anilinothiazolones as 11beta-HSD1 inhibitors., Yuan C, St Jean DJ Jr, Liu Q, Cai L, Li A, Han N, Moniz G, Askew B, Hungate RW, Johansson L, Tedenborg L, Pyring D, Williams M, Hale C, Chen M, Cupples R, Zhang J, Jordan S, Bartberger MD, Sun Y, Emery M, Wang M, Fotsch C, Bioorg Med Chem Lett. 2007 Nov 15;17(22):6056-61. Epub 2007 Sep 25. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17919905 17919905]
+The discovery of 2-anilinothiazolones as 11beta-HSD1 inhibitors., Yuan C, St Jean DJ Jr, Liu Q, Cai L, Li A, Han N, Moniz G, Askew B, Hungate RW, Johansson L, Tedenborg L, Pyring D, Williams M, Hale C, Chen M, Cupples R, Zhang J, Jordan S, Bartberger MD, Sun Y, Emery M, Wang M, Fotsch C, Bioorg Med Chem Lett. 2007 Nov 15;17(22):6056-61. Epub 2007 Sep 25. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17919905 17919905]
 [[Category: 11-beta-hydroxysteroid dehydrogenase]]
 [[Category: Homo sapiens]]
@@ Line 35: / Line 44: @@
 [[Category: transmembrane]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:46:11 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:34:24 2008''