Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site.
Article Details
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Weitz-Schmidt G, Welzenbach K, Brinkmann V, Kamata T, Kallen J, Bruns C, Cottens S, Takada Y, Hommel U
Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site.
Nat Med. 2001 Jun;7(6):687-92. doi: 10.1038/89058.
- PubMed ID
- 11385505 [ View in PubMed]
- Abstract
The beta2 integrin leukocyte function antigen-1 (LFA-1) has an important role in the pathophysiology of inflammatory and autoimmune diseases. Here we report that statin compounds commonly used for the treatment of hypercholesterolemia selectively blocked LFA-1-mediated adhesion and costimulation of lymphocytes. This effect was unrelated to the statins' inhibition of 3-hydroxy-3-methylglutaryl coenzyme-A reductase; instead it occurred via binding to a novel allosteric site within LFA-1. Subsequent optimization of the statins for LFA-1 binding resulted in potent, selective and orally active LFA-1 inhibitors that suppress the inflammatory response in a murine model of peritonitis. Targeting of the statin-binding site of LFA-1 could be used to treat diseases such as psoriasis, rheumatoid arthritis, ischemia/reperfusion injury and transplant rejection.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Lovastatin Integrin alpha-L Protein Humans UnknownInhibitorDetails Pitavastatin Integrin alpha-L Protein Humans UnknownNot Available Details Rosuvastatin Integrin alpha-L Protein Humans UnknownInhibitory allosteric modulatorDetails Simvastatin Integrin alpha-L Protein Humans UnknownInhibitory allosteric modulatorDetails