Development of ketobenzothiazole-based peptidomimetic TMPRSS13 inhibitors with low nanomolar potency.

ABSTRACT: TMPRSS13, a member of the Type II Transmembrane Serine Proteases (TTSP) family, is involved in cancer progression and in respiratory virus cell entry. To date, no inhibitors have been specifically developed for this protease. In this study, a chemical library of 65 ketobenzothiazole-based peptidomimetic molecules was screened against a proteolytically active form of recombinant TMPRSS13 to identify novel inhibitors. Following an initial round of screening, subsequent synthesis of additional derivatives supported by molecular modelling revealed important molecular determinants involved in TMPRSS13 inhibition. One inhibitor, N-0430, achieved low nanomolar affinity towards TMPRSS13 activity in a cellular context. Using a SARS-CoV-2 pseudovirus cell entry model, we further demonstrated the abi

SUBMITTER: Joushomme A 

PROVIDER: S-EPMC11843629 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature