The chemokine system and CCR5 antagonists: potential in HIV treatment and other novel therapies.
Since the recognition of human acquired immune deficiency syndrome, numerous classes of pharmacologic therapeutics have been developed to manage the disease. Current therapy includes co-administration of combinations of drugs classified by their mechanism of action as 'transcriptase inhibitors', 'protease inhibitors', 'integrase inhibitors' and the more recent 'fusion inhibitors'. This review focuses on the chemokine system and the recognition of chemokine receptors as targets for anti-human immunodeficiency virus (HIV) therapy. The FDA-approved chemokine (C-C motif) receptor 5 (CCR5) antagonist maraviroc (Selzentry) is discussed in detail, along with another compound vicriviroc, currently in clinical trials. The mechanism of action, pharmacokinetics, toxicity and current status of research on CCR5 antagonists is described. Further, potential therapeutic uses of these agents other than anti-HIV therapy are discussed.
Dhami
H
H
Temple University School of Pharmacy, Philadelphia, PA, USA.
Fritz
C E
CE
Gankin
B
B
Pak
S H
SH
Yi
W
W
Seya
M-J
MJ
Raffa
R B
RB
Nagar
S
S
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D065100:CCR5 Receptor Antagonists; D018925:Chemokines / Q000502:physiology*; D002986:Clinical Trials as Topic; D023581:HIV Fusion Inhibitors / Q000494:pharmacology; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000378:metabolism
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D018925:Chemokines; D023581:HIV Fusion Inhibitors; D019707:Receptors, Chemokine