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[摘要]：The prognosis for patients suffering from HIV-1 infection has improved since the introduction of highly active antiretroviral therapy. However, as the emergence of multidrug-resistant mutants often results in the failure of therapy, it seems mandatory to discover anti-HIV-1 agents with a novel mode of action. In this context, the essential steps of HIV-1 entry in the host cell offer several potential new targets for antiviral agents. In fact, an attempt to suppress R5 HIV-1 replication may be able to block viral transmission and delay disease progression. Therefore, chemokine CCR5 receptor antagonists have attracted a great deal of attention as novel anti-HIV-1 candidates. Cenicriviroc mesilate (TBR-652) is a highly potent and selective inhibitor of HIV-1 replication. In addition, cenicriviroc mesilate has the unique property of being a dual antagonist of the chemokine receptors CCR5, a coreceptor required for HIV infection, and CCR2, a coreceptor involved in metabolic and cardiovascular diseases. Ceniciriviroc mesilate is orally bioavailable and has a favorable pharmacokinetic profile in humans, and pharmacokinetic results support the feasibility of once-daily administration. It is also generally well tolerated, with no dose-limiting adverse events. |
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