AI Article Synopsis
- Lactoquinomycin and related compounds are identified as selective inhibitors of the AKT kinase, which is important in cancer cell signaling.
- Synthetic versions of these compounds were created, helping to outline their minimal active features and initial structure-activity relationships (SAR).
- The compounds show effectiveness against human tumor cells with active AKT and support a proposed mechanism where they work by bioreductive alkylation.
Article Abstract
The naturally occurring pyranonaphthoquinone (PNQ) antibiotic lactoquinomycin and related aglycones were found to be selective inhibitors of the serine-threonine kinase AKT. A set of synthetic PNQs were prepared and a minimum active feature set and preliminary SAR were determined. PNQ lactones inhibit the proliferation of human tumor cell lines containing constitutively activated AKT and show expected effects on cellular biomarkers. Biochemical data are presented supporting a proposed bioreductive alkylation mechanism of action.
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| http://dx.doi.org/10.1021/jm900075g | DOI Listing |
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