In Silico Discovery of Stapled Peptide Inhibitor Targeting the Nur77-PPARγ Interaction and Its Anti-Breast-Cancer Efficacy.

ABSTRACT: The binding of peroxisome proliferator-activated receptor γ (PPARγ) to the orphan nuclear receptor Nur77 facilitates the ubiquitination and degradation of Nur77, and leads to aberrant fatty acid uptake for breast cancer progression. Because of its crucial role in clinical prognosis, the interaction between Nur77 and PPARγ is an attractive target for anti-breast-cancer therapy. However, developing an inhibitor of the Nur77-PPARγ interaction poses a technical challenge due to the absence of the crystal structure of PPARγ and its corresponding interactive model with Nur77. Here, ST-CY14, a stapled peptide, is identified as a potent modulator of Nur77 with a K_D value of 3.247 × 10^-8 M by in silico analysis, rational design, and structural modification. ST-CY14 effectively

SUBMITTER: Bian H 

PROVIDER: S-EPMC11234460 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature