Development of N-(4-(1H-Imidazol-1-yl)phenyl)-4-chlorobenzenesulfonamide, a Novel Potent Inhibitor of β-Catenin with Enhanced Antitumor Activity and Metabolic Stability

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22310%2F24%3A43931122" target="_blank" >RIV/60461373:22310/24:43931122 - isvavai.cz</a>

Result on the web

<a href="https://pubs.acs.org/doi/full/10.1021/acs.jmedchem.4c01708" target="_blank" >https://pubs.acs.org/doi/full/10.1021/acs.jmedchem.4c01708</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jmedchem.4c01708" target="_blank" >10.1021/acs.jmedchem.4c01708</a>

Result language

angličtina

Original language name

Development of N-(4-(1H-Imidazol-1-yl)phenyl)-4-chlorobenzenesulfonamide, a Novel Potent Inhibitor of β-Catenin with Enhanced Antitumor Activity and Metabolic Stability

Original language description

The potential as a cancer therapeutic target of the recently reported hotspot binding region close to Lys508 of the beta-catenin armadillo repeat domain was not exhaustively explored. In order to get more insight, we synthesized novel N-(heterocyclylphenyl)benzenesulfonamides 6-28. The new compounds significantly inhibited Wnt-dependent transcription as well as SW480 and HCT116 cancer cell proliferation. Compound 25 showed binding mode consistent with this hotspot binding region. Compound 25 inhibited the growth of SW480 and HCT116 cancer cells with IC50&apos;s of 2 and 0.12 mu M, respectively, and was superior to the reference compounds 5 and 5-FU. 25 inhibited the growth of HCT-116 xenografted in BALB/Cnu/nu mice, reduced the expression of the proliferation marker Ki67, and significantly affected the expression of cancer-related genes. After incubation with human and mouse liver microsomes, 25 showed a higher metabolic stability than 5. Compound 25 aims to be a promising lead for the development of colorectal cancer anticancer therapies.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10401 - Organic chemistry

Project

—

Continuities

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

JOURNAL OF MEDICINAL CHEMISTRY

ISSN

0022-2623

e-ISSN

1520-4804

Volume of the periodical

67

Issue of the periodical within the volume

22

Country of publishing house

US - UNITED STATES

Number of pages

17

Pages from-to

20298-20314

UT code for WoS article

001350014100001

EID of the result in the Scopus database

2-s2.0-85208709914