alexa Cenicriviroc, an orally active CCR5 antagonist for the potential treatment of HIV infection.


Journal of Antivirals & Antiretrovirals

Author(s): Klibanov OM, Williams SH, Iler CA

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Abstract Treatment of HIV-1-infected individuals is often complicated by the development of antiretroviral resistance, and novel antiretroviral agents with unique mechanisms of action and resistance profiles are needed to address this issue. CCR5 inhibitors represent a new class of antiretroviral agents that block the CCR5 receptor and prevent HIV-1 recognition and entry into CD4+ macrophages and T-cells. Tobira Therapeutics Inc is developing cenicriviroc (TBR-652, formerly TAK-652), a potent inhibitor of CCR5-tropic HIV-1 replication. Cenicriviroc has good oral bioavailability, a long t1/2 that allows once-daily dosing, and has demonstrated excellent antiviral potency with minimal toxicity in in vitro studies and phase I clinical trials. Encouraging efficacy results have been reported from phase II clinical trials in patients with CCR5-tropic HIV-1. The drug is also an inhibitor of the CCR2 receptor, which is known to be associated with inflammatory-related disease states, leading to Tobira initiating a phase I clinical trial in patients with rheumatoid arthritis. Cenicriviroc is a promising CCR5 inhibitor with potentially important anti-inflammatory effects, and warrants further investigation.
This article was published in Curr Opin Investig Drugs and referenced in Journal of Antivirals & Antiretrovirals

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