NR4A1 Ligands as Potent Inhibitors of Breast Cancer Cell and Tumor Growth.

ABSTRACT: Nuclear receptor 4A1 (NR4A1, Nur77, TR3) is more highly expressed in breast and solid tumors compared to non-tumor tissues and is a pro-oncogenic factor in solid tumor-derived cancers. NR4A1 regulates cancer cell growth, survival, migration, and invasion, and bis-indole-derived compounds (CDIMs) that bind NR4A1 act as antagonists and inhibit tumor growth. Preliminary structure-binding studies identified 1,1-bis(3'-indolyl)-1-(3,5-disubstitutedphenyl)methane analogs as NR4A1 ligands with low K_D values; we further investigated the anticancer activity of the four most active analogs (K_D's ≤ 3.1 µM) in breast cancer cells and in athymic mouse xenograft models. The treatment of MDA-MB-231 and SKBR3 breast cancer cells with the 3-bromo-5-methoxy, 3-chloro-5-trifluoromethoxy

SUBMITTER: Karki K 

PROVIDER: S-EPMC8198788 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature