| InChI | InChI=1S/C28H38F3N5O2.C4H4O4/c1-19-16-35(14-15-36(19)24(17-38-5)22-6-8-23(9-7-22)28(29,30)31)27(4)10-12-34(13-11-27)26(37)25-20(2)32-18-33-21(25)3;5-3(6)1-2-4(7)8/h6-9,18-19,24H,10-17H2,1-5H3;1-2H,(H,5,6)(H,7,8)/b;2-1-/t19-,24-;/m0./s1 |
| Reference | 1. Expert Opin Drug Metab Toxicol. 2010 Sep;6(9):1139-50. doi:
10.1517/17425255.2010.510833.
<br><br>
Vicriviroc, a new CC-chemokine receptor 5 inhibitor for treatment of HIV:
properties, promises and challenges.
<br><br>
Lenz JC(1), Rockstroh JK.
<br>
Author information: <br>
(1)University of Bonn, Medicine I, Sigmund-Freudstr. 25, Bonn 53105, Germany.
<br>
IMPORTANCE OF THE FIELD: Although HIV has become a treatable disease with near to
normal life expectancy, the quest for the development of better tolerated drugs
with simple dosing schedules and a high barrier to the emergence of drug
resistance remains. Vicriviroc is a small-molecule chemokine receptor antagonist
that inhibits the binding of R5-tropic HIV-1 to host cells at the CC-chemokine
receptor 5 (CCR5) co-receptor, thus, preventing viral entry. CCR5 inhibitors are
believed to possibly decrease inflammation from the immune system and thereby
offer additional properties further to their antiretroviral efficacy.
AREAS COVERED IN THIS REVIEW: This review is based on a PubMed search covering
the years 2005 – 2010 for pharmacokinetic, pharmacological and clinical data of
vicriviroc.<br>
WHAT THE READER WILL GAIN: In this review, the pharmacokinetic, pharmacological
and clinical data of vicriviroc are presented. Moreover, the potential role of
vicriviroc in the growing HIV armamentarium is discussed.
TAKE HOME MESSAGE: Vicriviroc is being developed to be administered in
combination with a ritonavir-boosted protease inhibitor for patients with
R5-tropic virus. Early clinical trials have established the safety of vicriviroc
in both treatment-naive and -experienced R5-tropic HIV-1 infected individuals.
Recently, two Phase III clinical trials in treatment-experienced patients failed
to prove its superiority over available HIV medications. Phase III trials for
treatment-naive patients are still under planning. Clearly, more favorable study
results are needed to move vicriviroc into drug registration and approval.
<br><br>
2. Curr Opin Investig Drugs. 2009 Aug;10(8):845-59.
<br><br>
Vicriviroc, a CCR5 receptor antagonist for the potential treatment of HIV
infection.
<br><br>
Klibanov OM(1).
<br>
Author information: <br>
(1)Wingate University School of Pharmacy, Wingate, NC 28174-0159, USA.
[email protected]
<br>
Highly active antiretroviral therapy has revolutionized the care of patients with
HIV infection, but treatment is often complicated by the development of
antiretroviral resistance. CCR5 inhibitors are a novel class of antiretroviral
agents that block the CCR5 receptor, thereby preventing HIV-1 recognition and
entry into CD4+ macrophages and T-cells. Schering-Plough Corp is developing
vicriviroc, a CCR5 inhibitor that has demonstrated good oral bioavailability, has
a long half-life that allows once daily dosing, and is primarily metabolized by
cytochrome P450 CYP3A4. In vitro and clinical data suggest that vicriviroc has
excellent antiviral potency with minimal toxicity. Phase I and II clinical trials
demonstrated promising efficacy results when vicriviroc is administered to
patients infected with CCR5-tropic HIV-1. At the time of publication, phase III
trials were ongoing or planned to investigate the efficacy and safety of
vicriviroc in antiretroviral-naïve and -experienced patients infected with HIV-1.
<br>
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