3bgl
From Proteopedia
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|PDB= 3bgl |SIZE=350|CAPTION= <scene name='initialview01'>3bgl</scene>, resolution 2.225Å | |PDB= 3bgl |SIZE=350|CAPTION= <scene name='initialview01'>3bgl</scene>, resolution 2.225Å | ||
|SITE= <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> | |SITE= <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> | ||
| - | |LIGAND= <scene name='pdbligand=RID:'>RID</scene> | + | |LIGAND= <scene name='pdbligand=RID:(3R,5R)-7-[2-(4-FLUOROPHENYL)-5-(1-METHYLETHYL)-4-(MORPHOLIN-4-YLSULFONYL)-3-PHENYL-1H-PYRROL-1-YL]-3,5-DIHYDROXYHEPTANOIC+ACID'>RID</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= HMGCR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= HMGCR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2q1l|2Q1L]], [[2q6b|2Q6B]], [[2q6c|2Q6C]], [[2r4f|2R4F]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bgl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bgl OCA], [http://www.ebi.ac.uk/pdbsum/3bgl PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=3bgl RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
| + | |||
| + | ==Disease== | ||
| + | Known disease associated with this structure: Statins, attenuated cholesterol lowering by OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142910 142910]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Park, W K.C.]] | [[Category: Park, W K.C.]] | ||
[[Category: Pavlovsky, A.]] | [[Category: Pavlovsky, A.]] | ||
| - | [[Category: RID]] | ||
[[Category: alternative splicing]] | [[Category: alternative splicing]] | ||
[[Category: cholesterol biosynthesis]] | [[Category: cholesterol biosynthesis]] | ||
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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 Mon Mar 31 05:26:02 2008'' |
Revision as of 02:26, 31 March 2008
| |||||||
| , resolution 2.225Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , , and | ||||||
| Ligands: | |||||||
| Gene: | HMGCR (Homo sapiens) | ||||||
| Activity: | Hydroxymethylglutaryl-CoA reductase (NADPH), with EC number 1.1.1.34 | ||||||
| Related: | 2Q1L, 2Q6B, 2Q6C, 2R4F
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Hepatoselectivity of Statins: Design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors
Contents |
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.
Disease
Known disease associated with this structure: Statins, attenuated cholesterol lowering by OMIM:[142910]
About this Structure
3BGL is a Single protein structure of sequence from Homo sapiens. 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 Mon Mar 31 05:26:02 2008
Categories: Homo sapiens | Hydroxymethylglutaryl-CoA reductase (NADPH) | Single protein | Finzel, B C. | Park, W K.C. | Pavlovsky, A. | Alternative splicing | Cholesterol biosynthesis | Endoplasmic reticulum | Glycoprotein | Hmg-coa | Lipid synthesis | Membrane | Nadph | Oxidoreductase | Peroxisome | Polymorphism | Statin | Steroid biosynthesis | Transmembrane
