Abstract
Targeting KRAS-PDEδ protein-protein interactions with small molecules represents a promising opportunity for developing novel antitumor agents. However, current KRAS-PDEδ inhibitors are limited by poor cellular antitumor potency and the druggability of the target remains to be validated by new inhibitors. To tackle these challenges, herein, novel, highly potent KRAS-PDEδ inhibitors were identified by fragment-based drug design, providing promising lead compounds or chemical probes for investigating the biological functions and druggability of KRAS-PDEδ interaction.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Cell Line
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Cyclic Nucleotide Phosphodiesterases, Type 6 / antagonists & inhibitors*
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Drug Design
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Drug Discovery
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Humans
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MAP Kinase Signaling System / drug effects
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Oncogene Protein v-akt / drug effects
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Peptide Fragments / chemistry
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Protein Binding
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Proto-Oncogene Proteins p21(ras) / chemical synthesis*
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Reactive Oxygen Species / metabolism
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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KRAS protein, human
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Peptide Fragments
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Reactive Oxygen Species
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Oncogene Protein v-akt
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Cyclic Nucleotide Phosphodiesterases, Type 6
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Proto-Oncogene Proteins p21(ras)