Rational design of LEDGINs as first allosteric integrase inhibitors for the treatment of HIV infection

Belete A Desimmie; Jonas Demeulemeester; Frauke Christ; Zeger Debyser

doi:10.1016/j.ddtec.2012.10.002

Rational design of LEDGINs as first allosteric integrase inhibitors for the treatment of HIV infection

Drug Discov Today Technol. 2013 Dec;10(4):e517-22. doi: 10.1016/j.ddtec.2012.10.002.

Authors

Belete A Desimmie, Jonas Demeulemeester, Frauke Christ, Zeger Debyser

PMID: 24451643
DOI: 10.1016/j.ddtec.2012.10.002

Abstract

The interaction between lens epithelium-derived growth factor (LEDGF/p75) and HIV-1 integrase (IN) is an attractive target for antiviral development because its inhibition blocks HIV replication. Developing novel small molecules that disrupt the LEDGF/p75-IN interaction constitutes a promising new therapeutic strategy for the treatment of HIV. Here we will highlight recent advances in the design and development of small-molecule inhibitors binding to the LEDGF/p75 binding pocket of IN, referred to as LEDGINs.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Adaptor Proteins, Signal Transducing / metabolism*
Drug Design
HIV Infections / drug therapy*
HIV Integrase / metabolism*
HIV Integrase Inhibitors / therapeutic use*
HIV-1 / physiology
Humans
Transcription Factors / metabolism*

Substances

Adaptor Proteins, Signal Transducing
HIV Integrase Inhibitors
PSIP1 protein, human
Transcription Factors
HIV Integrase