Discovery of novel STAT3 inhibitors with anti-breast cancer activity: structure-based virtual screening, molecular dynamics and biological evaluation.

ABSTRACT: Triple negative breast cancer (TNBC) is a fatal type of breast cancer due to its high recurrence and metastatic potential. Persistent activation of signal transducer and activator of transcription 3 (STAT3) is crucial for TNBC progression, making it an attractive drug target. In this study, two new STAT3 inhibitors with significant anti-TNBC activity, d2 and d10, were identified from 1.67 million candidates through a rapid and cost-effective strategy integrating high-throughput virtual screening (HTVS), molecular mechanics/generalized born surface area (MM/GBSA), and binding pose metadynamics (BPMD) methods. In-depth mechanistic studies revealed that d2 and d10 significantly inhibited cell proliferation and colony formation, induced G1 phase arrest, and reduced migration and invasion of TN

SUBMITTER: Wang J 

PROVIDER: S-EPMC12013508 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature