3bgl

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spinqualitylabelsall models PDB ID 3bgl Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, 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 1 Overview 2 Disease 3 About this Structure 4 Reference

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

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