Recent progress in discovery of small-molecule CCR5 chemokine receptor ligands as HIV-1 inhibitors.
This review addresses key pharmacology and virology issues relevant in discovery and development of CCR5 antagonists as anti-HIV drugs, such as target validation, receptor internalization, allosterism, viral resistance and tropism. Recent progress in the discovery and development of CCR5 antagonists, SAR and clinical status are reviewed. Finally, modeling-based structure of CCR5 is discussed in the context of a small-molecule antagonism of the CCR5 receptor.
Kazmierski
Wieslaw
W
Department of Medicinal Chemistry, GlaxoSmithKline Research and Development, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA. wmk35860@gsk.com
Bifulco
Neil
N
Yang
Hanbiao
H
Boone
Larry
L
DeAnda
Felix
F
Watson
Chris
C
Kenakin
Terry
T
D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D001667:Binding, Competitive; D065100:CCR5 Receptor Antagonists; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D019713:Receptors, CCR5 / Q000502:physiology; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D008024:Ligands; D019713:Receptors, CCR5