alexa LEDGINs, non-catalytic site inhibitors of HIV-1 integrase: a patent review (2006 - 2014).
Infectious Diseases

Infectious Diseases

Journal of AIDS & Clinical Research

Author(s): Demeulemeester J, Chaltin P, Marchand A, De Maeyer M, Debyser Z, , Demeulemeester J, Chaltin P, Marchand A, De Maeyer M, Debyser Z,

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Abstract INTRODUCTION: 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. AREAS COVERED: 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). EXPERT OPINION: 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. This article was published in Expert Opin Ther Pat and referenced in Journal of AIDS & Clinical Research

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