Oxindol-3-ylidene inhibitors of AMP-activated protein kinase (AMPK)


The oral tyrosine kinase inhibitor sunitinib, used in the clinic to treat advanced renal cell carcinoma and gastrointestinal stromal tumors, is a potent AMPK inhibitor. However, sunitinib has been associated with clinical cardiac toxicity through non-specific binding to the AMPKα2 isoform. Dr. Philip Reigan and a team of researchers have revealed that the AMPKα1 isoform is predominantly expressed in cancer stem cells. Researchers are investigating increased selectivity for AMPK and the α1 isoform through structural modification of sunitinib. The potency of sunitinib and its selectivity for the α1 isoform supports its use as a basis for AMPK inhibitor development. Researchers have used a computation model of sunitinib docked into the crystal structure of AMPK to guide AMPK inhibitor development.


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For Information, Contact:
Mary Tapolsky
University of Colorado
Philip Reigan
Donald Backos
Christopher Matheson
Craig Jordan
Disease Areas:
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