Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10592826 | Bioorganic & Medicinal Chemistry Letters | 2014 | 4 Pages |
Abstract
The pyranonaphthoquinone (PNQ) lactone natural products, including 7-deoxykalafungin, have been reported to be potent and selective covalent inhibitors of AKT kinase. In this work we seek to identify structural features of the natural product scaffold that are essential for potency and selectivity. Using a deconstruction approach, we designed and prepared simplified analogues of 7-deoxykalafungin. Testing of the compounds for their ability to inhibit AKT and the closely related kinase PKA revealed that the 3,6-dihydro-2H-pyran ring of the PNQ lactones is required for potent and selective inhibition of AKT. We have also unexpectedly identified a new submicromolar inhibitor of PKA.
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Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Sudha Korwar, Thuy Nguyen, Keith C. Ellis,