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Updated: Nov 25, 2025

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
Published on: December 1, 2020
Structure-activity relationship studies of dipeptide-based hepsin inhibitors with Arg bioisosteres
Hongmok Kwon1, Hyunsoo Ha1, Hayoung Jeon1
1College of Pharmacy, Korea University, 2511 Sejong-ro, Jochiwon-eup, Sejong 30019, Republic of Korea.
Abstract:
Hepsin is a type II transmembrane serine protease (TTSP) associated with cell proliferation and overexpressed in several types of cancer including prostate cancer (PCa). Because of its significant role in cancer progression and metastasis, hepsin is an attractive protein as a potential therapeutic and diagnostic biomarker for PCa. Based on the reported Leu-Arg dipeptide-based hepsin inhibitors, we performed structural modification and determined in vitro hepsin- and matriptase-inhibitory activities. Comprehensive structure-activity relationship studies identified that the p-guanidinophenylalanine-based dipeptide analog 22a exhibited a strong hepsin-inhibitory activity (Ki = 50.5 nM) and 22-fold hepsin selectivity over matriptase. Compound 22a could be a prototype molecule for structural optimization of dipeptide-based hepsin inhibitors.
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