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Updated: May 26, 2026

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
Diketoacid inhibitors of HIV-1 integrase: from L-708,906 to raltegravir and beyond
K D Beare1, M J Coster, P J Rutledge
1School of Chemistry, The University of Sydney, NSW 2006, Australia.
Abstract:
HIV-1 integrase is one of the three viral enzymes essential to HIV replication. Consequently the development of therapeutics targeting this enzyme has been a major focus of antiretroviral research over the past two decades. Several classes of integrase inhibitors have been identified; of these the diketoacids (DKAs) show greatest promise: raltegravir (Merck & Co) has been approved by the US Food and Drug Administration (FDA) for HIV-1 therapy, while elvitegravir (Gilead Sciences/ Japan Tobacco) has reached phase III clinical trials. This review considers the development of DKA-based inhibitors from early screening studies through to the release of raltegravir. SAR data collated from numerous studies are compared and analysed, shedding light on the geometric and electronic requirements for effective binding to HIV-1 integrase. This information will in turn aid the rational design of future generations of integrase inhibitors.
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