title: Recent progress in discovery of small-molecule CCR5 chemokine receptor ligands as HIV-1 inhibitors.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, GlaxoSmithKline Research and Development, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA. wmk35860@gsk.com
authors.forename: Wieslaw
authors.initials: W
authors.lastname: Kazmierski
authors.forename: Neil
authors.initials: N
authors.lastname: Bifulco
authors.forename: Hanbiao
authors.initials: H
authors.lastname: Yang
authors.forename: Larry
authors.initials: L
authors.lastname: Boone
authors.forename: Felix
authors.initials: F
authors.lastname: DeAnda
authors.forename: Chris
authors.initials: C
authors.lastname: Watson
authors.forename: Terry
authors.initials: T
authors.lastname: Kenakin
mesh_terms: 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
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D008024:Ligands; D019713:Receptors, CCR5