en
Scientific article
Open access
English

Wnt-pathway inhibitors with selective activity against triple-negative breast cancer: from thienopyrimidine to quinazoline inhibitors

Published inFrontiers in pharmacology, vol. 13, 1045102
Publication date2022-10-28
First online date2022-10-28
Abstract

The Wnt-pathway has a critical role in development and tissue homeostasis and has attracted increased attention to develop anticancer drugs due to its aberrant activation in many cancers. In this study, we identified a novel small molecule series with a thienopyrimidine scaffold acting as a downstream inhibitor of the β-catenin-dependent Wnt-pathway. This novel chemotype was investigated using Wnt-dependent triple-negative breast cancer (TNBC) cell lines. Structure activity relationship (SAR) exploration led to identification of low micromolar compounds such as 5a , 5d , 5e and a novel series with quinazoline scaffold such as 9d . Further investigation showed translation of activity to inhibit cancer survival of HCC1395 and MDA-MB-468 TNBC cell lines without affecting a non-cancerous breast epithelial cell line MCF10a. This anti-proliferative effect was synergistic to docetaxel treatment. Collectively, we identified novel chemotypes acting as a downstream inhibitor of β-catenin-dependent Wnt-pathway that could expand therapeutic options to manage TNBC.

eng
Citation (ISO format)
BOUDOU, Cédric et al. Wnt-pathway inhibitors with selective activity against triple-negative breast cancer: from thienopyrimidine to quinazoline inhibitors. In: Frontiers in pharmacology, 2022, vol. 13, p. 1045102. doi: 10.3389/fphar.2022.1045102
Main files (1)
Article (Published version)
Secondary files (3)
Identifiers
ISSN of the journal1663-9812
127views
57downloads

Technical informations

Creation11/02/2022 10:13:00 AM
First validation11/02/2022 10:13:00 AM
Update time03/16/2023 8:46:25 AM
Status update03/16/2023 8:46:21 AM
Last indexation05/06/2024 11:58:09 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack