Hydrophobic Tagging-Induced Degradation of PDEδ in Colon Cancer Cells
Menglu Guo, Shipeng He, Junfei Cheng, Yu Li, Guoqiang Dong, Chunquan Sheng
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.
Topics & Concepts
Degradation (telecommunications)Colorectal cancerCancerComputer scienceChemistryCancer researchMedicineInternal medicineTelecommunicationsHER2/EGFR in Cancer ResearchMonoclonal and Polyclonal Antibodies ResearchCancer therapeutics and mechanisms