Atorvastatin
From Proteopedia
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2009 Sales: $12.7 Billion <ref>http://www.forbes.com/2008/06/18/pfizer-ranbaxy-lipitor-biz-healthcare-cx_mh_0618bizpfizer.html</ref> | 2009 Sales: $12.7 Billion <ref>http://www.forbes.com/2008/06/18/pfizer-ranbaxy-lipitor-biz-healthcare-cx_mh_0618bizpfizer.html</ref> | ||
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Atorvastatin is an inhibitor of [[HMG-CoA Reductase]], a highly regulated enzyme responsible for the committed step in cholesterol synthesis. Atorvastatin <scene name='HMG-CoA_Reductase/Statin_ator/7'>binds HMGR</scene> via a number of polar interactions with the "cis loop" of HMGR, particularly residues Ser 684, Asp 690, Lys 691, Lys 692, and hydrogen bond interactions between Glu 559 and Asp 767 with the O5-hydroxyl of the statins. Van der Waals interactions between Leu 562, Val 683, Leu 853, Ala 856, and Leu 857 of HMGR and hydrophobic ring structures of Atorvastatin contribute to binding as well.<ref>PMID:11349148</ref> These interactions help Atorvastatin outcompete outcompete HMG-CoA, the substrate of HMGR in binding to HMGR.<ref>PMID:7784310</ref> | Atorvastatin is an inhibitor of [[HMG-CoA Reductase]], a highly regulated enzyme responsible for the committed step in cholesterol synthesis. Atorvastatin <scene name='HMG-CoA_Reductase/Statin_ator/7'>binds HMGR</scene> via a number of polar interactions with the "cis loop" of HMGR, particularly residues Ser 684, Asp 690, Lys 691, Lys 692, and hydrogen bond interactions between Glu 559 and Asp 767 with the O5-hydroxyl of the statins. Van der Waals interactions between Leu 562, Val 683, Leu 853, Ala 856, and Leu 857 of HMGR and hydrophobic ring structures of Atorvastatin contribute to binding as well.<ref>PMID:11349148</ref> These interactions help Atorvastatin outcompete outcompete HMG-CoA, the substrate of HMGR in binding to HMGR.<ref>PMID:7784310</ref> | ||
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Revision as of 13:17, 8 November 2010
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Atorvastatin
Better Known As: Lipitor
Marketed By: Pfizer, Inc.
Major Indication: Hyperlipidemia & High Cholesterol (Hypercholesterolemia)
Date of FDA Approval: 1996
2009 Sales: $12.7 Billion [1]
Atorvastatin is an inhibitor of HMG-CoA Reductase, a highly regulated enzyme responsible for the committed step in cholesterol synthesis. Atorvastatin via a number of polar interactions with the "cis loop" of HMGR, particularly residues Ser 684, Asp 690, Lys 691, Lys 692, and hydrogen bond interactions between Glu 559 and Asp 767 with the O5-hydroxyl of the statins. Van der Waals interactions between Leu 562, Val 683, Leu 853, Ala 856, and Leu 857 of HMGR and hydrophobic ring structures of Atorvastatin contribute to binding as well.[2] These interactions help Atorvastatin outcompete outcompete HMG-CoA, the substrate of HMGR in binding to HMGR.[3]
- ↑ http://www.forbes.com/2008/06/18/pfizer-ranbaxy-lipitor-biz-healthcare-cx_mh_0618bizpfizer.html
- ↑ Istvan ES, Deisenhofer J. Structural mechanism for statin inhibition of HMG-CoA reductase. Science. 2001 May 11;292(5519):1160-4. PMID:11349148 doi:10.1126/science.1059344
- ↑ Corsini A, Maggi FM, Catapano AL. Pharmacology of competitive inhibitors of HMG-CoA reductase. Pharmacol Res. 1995 Jan;31(1):9-27. PMID:7784310
