Discovery of novel 2-hydroxydiarylamide derivatives as TMPRSS4 inhibitors

Sunghyun Kang; Hye-Jin Min; Min-Seo Kang; Myung-Geun Jung; Semi Kim

doi:10.1016/j.bmcl.2013.01.055

Discovery of novel 2-hydroxydiarylamide derivatives as TMPRSS4 inhibitors

Bioorg Med Chem Lett. 2013 Mar 15;23(6):1748-51. doi: 10.1016/j.bmcl.2013.01.055. Epub 2013 Feb 8.

Authors

Sunghyun Kang¹, Hye-Jin Min, Min-Seo Kang, Myung-Geun Jung, Semi Kim

Affiliation

¹ Biomedical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejon 305-806, Republic of Korea.

PMID: 23414802
DOI: 10.1016/j.bmcl.2013.01.055

Abstract

TMPRSS4 is a novel type II transmembrane serine protease that has been implicated in the invasion and metastasis of colon cancer cells. In this study, a novel series of 2-hydroxydiarylamide derivatives were synthesized and evaluated for inhibiting TMPRSS4 serine protease activity and suppressing cancer cell invasion. These derivatives demonstrated good inhibitory activity against TMPRSS4 serine protease, which correlated with the promising anti-invasive activity of colon cancer cells overexpressing TMPRSS4.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amides / chemistry*
Amides / metabolism
Amides / toxicity
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / therapeutic use
Cell Line, Tumor
Cell Survival / drug effects
Colonic Neoplasms / drug therapy
Drug Evaluation, Preclinical
Humans
Membrane Proteins / antagonists & inhibitors*
Membrane Proteins / metabolism
Protein Binding
Serine Endopeptidases / metabolism
Serine Proteinase Inhibitors / chemistry*
Serine Proteinase Inhibitors / metabolism
Serine Proteinase Inhibitors / toxicity
Structure-Activity Relationship

Substances

Amides
Antineoplastic Agents
Membrane Proteins
Serine Proteinase Inhibitors
Serine Endopeptidases
TMPRSS4 protein, human