2. Academic Validation
  3. Hydrophobic Tagging-Induced Degradation of PDEδ in Colon Cancer Cells

Hydrophobic Tagging-Induced Degradation of PDEδ in Colon Cancer Cells

  • ACS Med Chem Lett. 2022 Jan 12;13(2):298-303. doi: 10.1021/acsmedchemlett.1c00670.
Menglu Guo 1,  Shipeng He 2,  Junfei Cheng 1,  Yu Li 1,  Guoqiang Dong 1,  Chunquan Sheng 1
Affiliations

Affiliations

  • 1 School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
  • 2 Institute of Translational Medicine, Shanghai University, Shanghai 200444, China.
PMID: 35178186 DOI: 10.1021/acsmedchemlett.1c00670
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.

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