Nur77 antagonist 1 (Compound ja) is a selective Nur77 antagonist (K D SPR Nur77 = 91 nM) that induces cancer cell apoptosis and exhibits excellent antitumor activity against triple-negative breast cancer (TNBC) cells [1].

Nur77 antagonist 1 (Compound ja) exhibits selective antiproliferative activity against tumor cells from various tissues, showing higher selectivity for TNBC cell lines (MDA-MB-231, HCC-1806, and BT549 with IC50 values of 0.40 ± 0.03, 0.38 ± 0.08, and 2.12 ± 0.15, respectively) than for the human normal breast cell line (MCF-10A, IC50 of 48.01 ± 2.86) [1]. At concentrations of 0-2 μM for 6 hours, it induces apoptosis in MDA-MB-231-sictr cells in a Nur77-dependent manner [1]. When used at concentrations of 0-5 μM for 6 hours, it triggers Nur77-dependent cell cycle arrest and apoptosis in MDA-MB-231 cells by mediating TP53 phosphorylation pathways [1]. Western blot analysis demonstrates that Nur77 antagonist 1 prompts extrinsic Nur77 degradation and PARP cleavage in a dose- and time-dependent manner [1]. Apoptosis analysis of MDA-MB-231 cells reveals apoptotic cell percentages of 15.10, 25.38, 40.01, 54.83, and 74.62% at concentrations of 0.32, 0.63, 1.25, 2.5, and 5.0 μM, respectively [1].

Nur77 antagonist 1 (Compound ja) administered at 10 mg/kg via intraperitoneal injection demonstrates significant antitumor efficacy and excellent in vivo tolerance in the breast cancer MDA-MB-231 xenograft nude mice model. Additionally, at concentrations of 1.25-5 μM, this compound shows strong in vivo safety in zebrafish embryo models. In the animal model, treatment results in reduced tumor weight and volume, achieving a tumor growth inhibition (TGI) of 99.95%, and leads to increased cleaved caspase 3 while decreasing Ki67 expression in tumor tissues.