Discovery of novel dual-target inhibitors of LSD1/EGFR for non-small cell lung cancer therapy.

ABSTRACT: Histone lysine-specific demethylase 1 (LSD1) is overexpressed in various solid and hematological tumors, suggesting its potential as a therapeutic target, but there are currently no LSD1 inhibitors available on the market. In this study we employed a computer-guided approach to identify novel LSD1/EGFR dual inhibitors as a potential therapeutic agent for non-small cell lung cancer. Through a multi-stage virtual screening approach, we found L-1 and L-6, two compounds with unique scaffolds that effectively inhibit LSD1 with IC₅₀ values of 6.24 and 9.26 μM, respectively. Using molecular similarity-based screening, 48 analogs of L-1 and L-6 were retrieved from ChemDiv library, 18 analogs were selected for biological activity analysis. Eight compounds showed weaker inhibitory activit

SUBMITTER: Wei Y 

PROVIDER: S-EPMC11950244 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature