Design, synthesis, and biological evaluation of benzodiazepine-based SUMO-specific protease 1 inhibitors.
As the best-characterized ubiquitin-like protein (UBL), small ubiquitin-related modifier (SUMO) was found to conjugate with a number of proteins to regulate cellular functions including transcription, signal transduction, and cell cycle. While E1, E2 and E3 ligases are responsible for the forward SUMOylation reaction, SUMO-specific proteases (SENPs) reversibly remove SUMO from ... the SUMOylated proteins. Recently, SENP1 was found to be a potential therapeutic target for the treatment of prostate cancers, but the design and synthesis of its inhibitors have not been reported. We designed and synthesized a series of benzodiazepine-based SENP1 inhibitors, and they showed inhibitory activity as good as IC(50)=9.2?M (compound 38). The structure-activity relationship was also discussed.
Mesh Terms:
Cell Line, Tumor, Drug Design, Drug Evaluation, Preclinical, Electrophoresis, Polyacrylamide Gel, Humans, Hydrogen Bonding, Inhibitory Concentration 50, Models, Molecular, Protease Inhibitors, Small Ubiquitin-Related Modifier Proteins
Cell Line, Tumor, Drug Design, Drug Evaluation, Preclinical, Electrophoresis, Polyacrylamide Gel, Humans, Hydrogen Bonding, Inhibitory Concentration 50, Models, Molecular, Protease Inhibitors, Small Ubiquitin-Related Modifier Proteins
Bioorg Med Chem Lett
Date: Nov. 01, 2011
PubMed ID: 21930380
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