2rbe
From Proteopedia
(New page: 200px<br /><applet load="2rbe" size="350" color="white" frame="true" align="right" spinBox="true" caption="2rbe, resolution 1.900Å" /> '''The discovery of 2-...) |
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==Overview== | ==Overview== | ||
| - | A series of 2-anilinothiazolones were prepared as inhibitors of | + | 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== | ==About this Structure== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Jordan, S | + | [[Category: Jordan, S R.]] |
[[Category: Li, V.]] | [[Category: Li, V.]] | ||
[[Category: Zhang, J.]] | [[Category: Zhang, J.]] | ||
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[[Category: transmembrane]] | [[Category: transmembrane]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:46:11 2008'' |
Revision as of 16:46, 21 February 2008
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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 with and as ligands. Active as 11-beta-hydroxysteroid dehydrogenase, with EC number 1.1.1.146 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
Page seeded by OCA on Thu Feb 21 18:46:11 2008
Categories: 11-beta-hydroxysteroid dehydrogenase | Homo sapiens | Single protein | Jordan, S R. | Li, V. | Zhang, J. | NDP | ZMG | 3-layer(aba) sandwich | Alpha beta | Endoplasmic reticulum | Glycoprotein | Lipid metabolism | Membrane | Microsome | Nad(p)-binding rossmann-like domain | Nadp | Oxidoreductase | Polymorphism | Rossmann fold | Signal-anchor | Steroid metabolism | Transmembrane
