2rbe

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[[Image:2rbe.jpg|left|200px]]<br /><applet load="2rbe" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:2rbe.jpg|left|200px]]
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caption="2rbe, resolution 1.900&Aring;" />
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'''The discovery of 2-anilinothiazolones as 11beta-HSD1 inhibitors'''<br />
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{{Structure
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|PDB= 2rbe |SIZE=350|CAPTION= <scene name='initialview01'>2rbe</scene>, resolution 1.900&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=ZMG:'>ZMG</scene> and <scene name='pdbligand=NDP:NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE'>NDP</scene>
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|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]
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|GENE= HSD11B1, HSD11, HSD11L ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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}}
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'''The discovery of 2-anilinothiazolones as 11beta-HSD1 inhibitors'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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2RBE 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].
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2RBE 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==
==Reference==
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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]
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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: 11-beta-hydroxysteroid dehydrogenase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: transmembrane]]
[[Category: transmembrane]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:46:11 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:34:24 2008''

Revision as of 16:34, 20 March 2008

Image:2rbe.jpg


PDB ID 2rbe

Drag the structure with the mouse to rotate
, 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


Overview

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 Structure

2RBE is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from 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:17919905

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