Dr. Philip Reigan and a team of researchers are developing novel oxindole-based inhibitors of 5' AMP-activated protein kinase (AMPK), a kinase with a critical function in metabolic regulation. An extension of developing AMPK inhibitors is to couple these inhibitors to a the cereblon (CRBN)-binding ligand, pomalidomide, as a PROteolysis TArgeting Chimera (PROTAC) strategy. This approach will enable binding of the inhibitor to AMPK and the conjugated PROTAC will target the protein for degradation in the cell. In addition to this approach, the team has also proposed to incorporate a nitroimidazole bioreductive prodrug moiety to the inhibitor and/or PROTAC group to develop a first in class series of hypoxia-activated PROTACs.
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