(Thio)chromenone derivatives exhibit anti-metastatic effects through selective inhibition of uPAR in cancer cell lines: discovery of an uPAR-targeting fluorescent probe

So-Young Chun; Chanhee Park; Jiwon Oh; Hey-Jin Yoon; Tae-il Kim; Youngmi Kim; Seung Wook Ham; Hye Ran Koh; Hyung Ho Lee; Hun Young Kim; Kyungsoo Oh

doi:10.1039/D4CC05907G

(Thio)chromenone derivatives exhibit anti-metastatic effects through selective inhibition of uPAR in cancer cell lines: discovery of an uPAR-targeting fluorescent probe†

So-Young Chun,^a Chanhee Park,^a Jiwon Oh,

^b Hey-Jin Yoon,^c Tae-il Kim,^d Youngmi Kim,

^d Seung Wook Ham,^e Hye Ran Koh,^e Hyung Ho Lee,^c Hun Young Kim

*^f and Kyungsoo Oh

*^a

Author affiliations

* Corresponding authors

^a Center for Metareceptome Research, Graduate School of Pharmaceutical Sciences, Chung-Ang University, 84 Heukseok-ro, Dongjak, Seoul 06974, Republic of Korea
E-mail: kyungsoooh@cau.ac.kr

^b Department of Integrative Energy Engineering, Graduate School of Energy and Environment (KU-KIST Green School), College of Engineering, Korea University, Seoul 02841, Republic of Korea

^c Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 08826, Republic of Korea

^d Department of Chemistry, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea

^e Department of Chemistry, Chung-Ang University, 84 Heukseok-ro, Dongjak, Seoul 06974, Republic of Korea

^f Department of Global Innovative Drugs, Chung-Ang University, 84 Heukseok-ro, Dongjak, Seoul 06974, Republic of Korea
E-mail: hunykim@cau.ac.kr

Abstract

A class of (thio)chromenone derivatives has been identified as suitable ligands for uPAR, a glycoprotein with a prognostic value in a large number of human cancers. The (thio)chromenone agents actively inhibited the binding of uPAR to uPA with a binding affinity of 18.6 nM, reducing cell migration in the wound healing assay by up to 40% without apparent cell motility. The discovery of an uPAR-targeting fluorescent probe was also made in this study that can selectively bind to the membrane uPAR, providing valuable molecular insights into the role of uPAR in cancer metastasis. This study should serve as a basis for the development of new uPAR-targeting agents that can control the metastatic potential of cancer cells with minimal cytotoxicity.

This article is part of the themed collections: ChemComm Most Popular 2024 Articles and ChemComm 60th Anniversary Collection

Chemical Communications

(Thio)chromenone derivatives exhibit anti-metastatic effects through selective inhibition of uPAR in cancer cell lines: discovery of an uPAR-targeting fluorescent probe†

Abstract

Associated articles

Supplementary files

Article information

Download Citation

Permissions

(Thio)chromenone derivatives exhibit anti-metastatic effects through selective inhibition of uPAR in cancer cell lines: discovery of an uPAR-targeting fluorescent probe

Social activity

Search articles by author

Spotlight

Advertisements