Hydrophobic Tagging-Induced Degradation of PDEδ in Colon Cancer Cells.

Basic Information

ID: ALA5038671

Journal: ACS Med Chem Lett

Title: Hydrophobic Tagging-Induced Degradation of PDEδ in Colon Cancer Cells.

Authors: Guo M, He S, Cheng J, Li Y, Dong G, Sheng C.

Abstract: The development of KRAS-PDEδ protein-protein interaction (PPI) inhibitors is generally hampered by limited antitumor activity. Herein, the first hydrophobic tagging (HyT)-based PDEδ degraders were designed. Compound 17c efficiently bound to PDEδ and induced degradation of PDEδ in SW480 colon cancer cells. As compared with PDEδ inhibitor deltazinone, HyT-based degrader 17c exhibited improved antitumor activity toward KRAS mutant cancer cells. This study highlighted the potential of HyT as a valuable chemical tool for tumorigenic PDEδ knockdown, which could be developed into a promising strategy for antitumor drug discovery.

CiteXplore: 35178186

DOI: 10.1021/acsmedchemlett.1c00670

Patent ID: