Comparative analysis for optimal LSD1 inhibitors evaluation techniques: pros and cons.

Aberrant expression of lysine-specific demethylase 1 (LSD1) has been consistently implicated in a broad spectrum of malignancies, underscoring its relevance as a therapeutic target. Despite growing interest, the development of LSD1 inhibitors continues to face significant challenges, in part due to the enzyme's dual role in catalysis and as a scaffolding protein within chromatin-remodeling complexes. Recent insights into the non-enzymatic functions of LSD1 have shifted the focus toward disrupting its protein-protein interactions, particularly with chromatin-modifying enzymes, as a complementary or alternative therapeutic strategy. In light of the limited systematic evaluation of available technologies, this work provides a critical overview and comparative analysis of current screening platforms and binding affinity assays, with particular attention to approaches capable of identifying LSD1 scaffold inhibitors. These efforts aim to accelerate the discovery of next-generation LSD1-targeted therapies with improved translational potential in oncology.