3bgl
From Proteopedia
(New page: 200px<br /><applet load="3bgl" size="350" color="white" frame="true" align="right" spinBox="true" caption="3bgl, resolution 2.225Å" /> '''Hepatoselectivity o...) |
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==Overview== | ==Overview== | ||
| - | 4-Sulfamoyl pyrroles were designed as novel hepatoselective HMG-CoA | + | 4-Sulfamoyl pyrroles were designed as novel hepatoselective HMG-CoA reductase inhibitors (statins) to reduce myalgia, a statin-induced adverse effect. The compounds were prepared via a [3+2] cycloaddition of a Munchnone with a sulfonamide-substituted alkyne. We identified compounds with greater selectivity for hepatocytes compared to L6-myocytes than rosuvastatin and atorvastatin. There was an inverse correlation of myocyte potencies and ClogP values. A number of analogs were effective at reducing cholesterol in acute and chronic in vivo models but they lacked sufficient chronic in vivo activity to warrant further development. |
==About this Structure== | ==About this Structure== | ||
| - | 3BGL 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=RID:'>RID</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_reductase_(NADPH) Hydroxymethylglutaryl-CoA reductase (NADPH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.34 1.1.1.34] Known structural/functional Sites: <scene name='pdbsite=AC1:Rid Binding Site For Residue A 2'>AC1</scene>, <scene name='pdbsite=AC2:Rid Binding Site For Residue B 1'>AC2</scene>, <scene name='pdbsite=AC3:Rid Binding Site For Residue C 4'>AC3</scene> and <scene name='pdbsite=AC4:Rid Binding Site For Residue D 3'>AC4</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BGL OCA]. | + | 3BGL 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=RID:'>RID</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_reductase_(NADPH) Hydroxymethylglutaryl-CoA reductase (NADPH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.34 1.1.1.34] Known structural/functional Sites: <scene name='pdbsite=AC1:Rid+Binding+Site+For+Residue+A+2'>AC1</scene>, <scene name='pdbsite=AC2:Rid+Binding+Site+For+Residue+B+1'>AC2</scene>, <scene name='pdbsite=AC3:Rid+Binding+Site+For+Residue+C+4'>AC3</scene> and <scene name='pdbsite=AC4:Rid+Binding+Site+For+Residue+D+3'>AC4</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BGL OCA]. |
==Reference== | ==Reference== | ||
| - | Hepatoselectivity of statins: | + | Hepatoselectivity of statins: design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors., Park WK, Kennedy RM, Larsen SD, Miller S, Roth BD, Song Y, Steinbaugh BA, Sun K, Tait BD, Kowala MC, Trivedi BK, Auerbach B, Askew V, Dillon L, Hanselman JC, Lin Z, Lu GH, Robertson A, Sekerke C, Bioorg Med Chem Lett. 2008 Feb 1;18(3):1151-6. Epub 2007 Dec 5. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18155906 18155906] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Hydroxymethylglutaryl-CoA reductase (NADPH)]] | [[Category: Hydroxymethylglutaryl-CoA reductase (NADPH)]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Finzel, B | + | [[Category: Finzel, B C.]] |
| - | [[Category: Park, W | + | [[Category: Park, W K.C.]] |
[[Category: Pavlovsky, A.]] | [[Category: Pavlovsky, A.]] | ||
[[Category: RID]] | [[Category: RID]] | ||
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[[Category: transmembrane]] | [[Category: transmembrane]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:05:35 2008'' |
Revision as of 17:05, 21 February 2008
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Hepatoselectivity of Statins: Design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors
Overview
4-Sulfamoyl pyrroles were designed as novel hepatoselective HMG-CoA reductase inhibitors (statins) to reduce myalgia, a statin-induced adverse effect. The compounds were prepared via a [3+2] cycloaddition of a Munchnone with a sulfonamide-substituted alkyne. We identified compounds with greater selectivity for hepatocytes compared to L6-myocytes than rosuvastatin and atorvastatin. There was an inverse correlation of myocyte potencies and ClogP values. A number of analogs were effective at reducing cholesterol in acute and chronic in vivo models but they lacked sufficient chronic in vivo activity to warrant further development.
About this Structure
3BGL is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Hydroxymethylglutaryl-CoA reductase (NADPH), with EC number 1.1.1.34 Known structural/functional Sites: , , and . Full crystallographic information is available from OCA.
Reference
Hepatoselectivity of statins: design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors., Park WK, Kennedy RM, Larsen SD, Miller S, Roth BD, Song Y, Steinbaugh BA, Sun K, Tait BD, Kowala MC, Trivedi BK, Auerbach B, Askew V, Dillon L, Hanselman JC, Lin Z, Lu GH, Robertson A, Sekerke C, Bioorg Med Chem Lett. 2008 Feb 1;18(3):1151-6. Epub 2007 Dec 5. PMID:18155906
Page seeded by OCA on Thu Feb 21 19:05:35 2008
Categories: Homo sapiens | Hydroxymethylglutaryl-CoA reductase (NADPH) | Single protein | Finzel, B C. | Park, W K.C. | Pavlovsky, A. | RID | Alternative splicing | Cholesterol biosynthesis | Endoplasmic reticulum | Glycoprotein | Hmg-coa | Lipid synthesis | Membrane | Nadph | Oxidoreductase | Peroxisome | Polymorphism | Statin | Steroid biosynthesis | Transmembrane
