The treatment of HIV-1/AIDS has achieved great success, partly owing to the clinical applications of HIV-1 integrase (IN) strand transfer inhibitors (INSTIs). After briefly introducing HIV-1/AIDS and its treatment, this chapter discusses the medical applications and limitations of five US Food and Drug Administration–approved INSTIs for the treatment of HIV/AIDS and preexposure prophylaxis for HIV-1. The development of authentic HIV-1 IN inhibitors, which include two main categories, INSTIs and IN-LEDGF/p75 allosteric inhibitors, is then reviewed. Pharmacophore and binding modes of INSTIs are provided, which are helpful for designing and identifying better novel INSTIs that may overcome the emergence of resistance to marketed INSTIs.
Privileged Scaffolds in Drug Discovery 2023, Pages 377-390,