CCR5 antagonist

A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity. Proc. Natl. AcadSci. USA 96 5698-5703. 

Lalezari J, Thompson M, Kumar P, PUiero P, Davey R, Patterson K, Shachoy-Clark A, Adkison K, Demarest J, Lou Y, Berrey M, Piscitelh S (2005a) Antiviral activity and safety of 873140, a novel CCR5 antagonist, during short-term monotherapy in HIV-infected adults. Aids 19 1443-1448... 

Westby M, Smith-Burchnell C, Mori J, Lewis M, Mosley M, Stockdale M, Dorr P, Ciaramella G, Perros M (2007) Reduced maximal inhibition in phenotypic susceptibility assays indicates that viral strains resistant to the CCR5 antagonist maraviroc utilize inhibitor-bound receptor for entry, J Virol 81 2359-2371... 

CCR5 expression likely plays a role in T-cell recruitment and may be involved in the development of autoimmune diseases. There is a negative association between the CCR5A32 mutation and rheumatoid arthritis (Prahalad 2006). Furthermore, additional studies reviewed elsewhere suggest the involvement of CCR5 in multiple sclerosis, diabetes, and transplant rejection (Ribeiro and Horuk 2005). As such, it is likely that CCR5 antagonists developed for the treatment of HIV-1 infection can also be used for other diseases. 

CCR5 CIA DBA/1 mice A nonpeptide CCR5 antagonist, TAK-779. Also inhibits CXCR3. 

Fatkenheuer G, Pozniak AL, Johnson MA, et al. Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1. Nat Med 2005 11(11) 1170-1172. 

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