Structure-activity relationship studies of dipeptide-based hepsin inhibitors with Arg bioisosteres.
Bioorg Chem
; 107: 104521, 2021 02.
Article
em En
| MEDLINE
| ID: mdl-33334587
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Serina Endopeptidases
/
Inibidores de Serina Proteinase
/
Dipeptídeos
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article