2Q6B

Design and synthesis of novel, conformationally restricted HMG-COA reductase inhibitors

Summary for 2Q6B

• Entry DOI: 10.2210/pdb2q6b/pdb
• Related: 2Q1L 2Q6C
• Descriptor: 3-hydroxy-3-methylglutaryl-coenzyme A reductase, SULFATE ION, (3R,5R)-7-[3-(4-FLUOROPHENYL)-1-ISOPROPYL-8-OXO-7-PHENYL-1,4,5,6,7,8-HEXAHYDROPYRROLO[2,3-C]AZEPIN-2-YL]-3,5-DIHYDROXYHEPTANOIC ACID, ... (4 entities in total)
• Functional Keywords: oxidoreductase, cholesterol biosynthesis, hmg-coa, nadph, statin
• Biological source: Homo sapiens (human)
• Cellular location: Endoplasmic reticulum membrane; Multi-pass membrane protein: P04035
• Total number of polymer chains: 4
• Total formula weight: 192392.89

Authors

Pavlovsky, A.,Pfefferkorn, J.A.,Harris, M.S.,Finzel, B.C. (deposition date: 2007-06-04, release date: 2007-07-17, Last modification date: 2024-02-21)

Primary citation

Pfefferkorn, J.A.,Choi, C.,Song, Y.,Trivedi, B.K.,Larsen, S.D.,Askew, V.,Dillon, L.,Hanselman, J.C.,Lin, Z.,Lu, G.,Robertson, A.,Sekerke, C.,Auerbach, B.,Pavlovsky, A.,Harris, M.S.,Bainbridge, G.,Caspers, N.
Design and synthesis of novel, conformationally restricted HMG-CoA reductase inhibitors.
Bioorg.Med.Chem.Lett., 17:4531-4537, 2007

PubMed Abstract: Using structure-based design, a novel series of conformationally restricted, pyrrole-based inhibitors of HMG-CoA reductase were discovered. Leading analogs demonstrated potent inhibition of cholesterol synthesis in both in vitro and in vivo models and may be useful for the treatment of hypercholesterolemia and related lipid disorders.

PubMed: 17574411
DOI: 10.1016/j.bmcl.2007.05.097

Experimental method

X-RAY DIFFRACTION (2 Å)