Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site.

Article Details

Citation

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
DrugTargetKindOrganismPharmacological ActionActions
LovastatinIntegrin alpha-LProteinHumans
Unknown
Inhibitor
Details
PitavastatinIntegrin alpha-LProteinHumans
Unknown
Not AvailableDetails
RosuvastatinIntegrin alpha-LProteinHumans
Unknown
Inhibitory allosteric modulator
Details
SimvastatinIntegrin alpha-LProteinHumans
Unknown
Inhibitory allosteric modulator
Details