Preclinical discovery and development of maraviroc for the treatment of HIV

Expert Opin Drug Discov. 2015 Jun;10(6):671-84. doi: 10.1517/17460441.2015.1041497. Epub 2015 Apr 30.

Abstract

Introduction: Maraviroc is a first-in-class antiretroviral (ARV) drug acting on a host cell target (CCR5), which blocks the entry of the HIV virus into the cell. Maraviroc is currently indicated for combination ARV treatment in adults infected only with CCR5-tropic HIV-1.

Areas covered: This drug discovery case history focuses on the key studies that led to the discovery and approval of maraviroc, as well as on post-launch clinical reports. The article is based on the data reported in published preclinical and clinical studies, conference posters and on drug package data.

Expert opinion: The profound understanding of HIV's entry mechanisms has provided a strong biological rationale for targeting the chemokine receptor CCR5. The CCR5-antagonist mariviroc, with its unique mode of action and excellent safety profile, is an important therapeutic option for HIV patients. In general, the authors believe that targeting host factors is a useful approach for combating new and re-emerging transmissible diseases, as well as pathogens that easily become resistant to common antiviral drugs. Maraviroc, offering a potent and safe cellular receptor-mediated pharmacological response to HIV, has paved the way for the development of a new generation of host-targeting antivirals.

Keywords: CCR5-receptor antagonist; HIV-1; antiretroviral therapy; entry inhibitor; maraviroc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use
  • CCR5 Receptor Antagonists / administration & dosage
  • CCR5 Receptor Antagonists / pharmacology
  • CCR5 Receptor Antagonists / therapeutic use*
  • Cyclohexanes / administration & dosage
  • Cyclohexanes / pharmacology
  • Cyclohexanes / therapeutic use*
  • Drug Approval
  • Drug Discovery / methods
  • Drug Evaluation, Preclinical / methods
  • Drug Therapy, Combination
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / drug effects
  • HIV-1 / isolation & purification
  • Humans
  • Maraviroc
  • Triazoles / administration & dosage
  • Triazoles / pharmacology
  • Triazoles / therapeutic use*

Substances

  • Anti-HIV Agents
  • CCR5 Receptor Antagonists
  • Cyclohexanes
  • Triazoles
  • Maraviroc