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

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.

SUBMITTER: Guo M

PROVIDER: S-EPMC8842115 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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

Guo Menglu M He Shipeng S Cheng Junfei J Li Yu Y Dong Guoqiang G Sheng Chunquan C

ACS medicinal chemistry letters 20220112 2

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 <b>17c</b> efficiently bound to PDEδ and induced degradation of PDEδ in SW480 colon cancer cells. As compared with PDEδ inhibitor deltazinone, HyT-based degrader <b>17c</b> exhibited improved antitumor activity toward KRAS mutant cancer cells. This study highlighted the potential of ...[more]

PMID: 35178186

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