title: LEDGINs, non-catalytic site inhibitors of HIV-1 integrase: a patent review (2006 - 2014).
abstract: BACKGROUND
  Integration of the viral genome into the host cell chromatin is a central step in the replication cycle of the HIV. Blocking the viral integrase (IN) enzyme therefore provides an attractive therapeutic strategy, as evidenced by the recent clinical approval of three IN strand transfer inhibitors. Viral resistance and cross-resistance among these inhibitors, however, warrant the search for compounds targeting HIV integration through alternative mechanisms of action.
  
  
  METHODS
  The most potent class of allosteric IN inhibitors was independently identified at the University of Leuven, Belgium, and at Boehringer Ingelheim, Canada. These compounds, coined LEDGINs (after the lens epithelium-derived growth factor/p75 cofactor binding pocket on IN) or non-catalytic site IN inhibitors (NCINIs) by the respective groups, have shown remarkable antiviral activity. This review provides a brief introduction to the compound class and discusses the recent patent literature (2006 to the present).
  
  
  CONCLUSIONS
  LEDGINs are still early in development. Trials with clinical candidate BI-224436 were put on hold despite promising results. Literature, however, reveals that almost all major pharmaceutical companies active in the treatment of HIV/AIDS have taken a significant interest in this class. As a result, several of these inhibitors may soon enter clinical trials.
authors.affiliation: KU Leuven, Laboratory for Biomolecular Modeling, Department of Chemistry , Leuven , Belgium.
authors.forename: Jonas
authors.initials: J
authors.lastname: Demeulemeester
authors.forename: Patrick
authors.initials: P
authors.lastname: Chaltin
authors.forename: Arnaud
authors.initials: A
authors.lastname: Marchand
authors.forename: Marc
authors.initials: M
authors.lastname: De Maeyer
authors.forename: Zeger
authors.initials: Z
authors.lastname: Debyser
authors.forename: Frauke
authors.initials: F
authors.lastname: Christ
mesh_terms: D055808:Drug Discovery; D019428:HIV Integrase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D057166:High-Throughput Screening Assays; D010330:Patents as Topic
chemical_list: D019428:HIV Integrase Inhibitors
keywords: AIDS; HIV; LEDGIN; allosteric; combination antiretroviral therapy; integrase; lens epithelium-derived growth factor/p75; maturation; non-catalytic site integrase inhibitor