ML346

ML346 (CAS No.: 100872-83-1) is a small-molecule modulator of proteostasis that functions as an activator of heat shock protein 70 (Hsp70) expression through stimulation of heat shock factor 1 (HSF-1)–dependent transcriptional activity. It enhances the cellular heat shock response by inducing the expression of molecular chaperones, including Hsp70, Hsp40, and Hsp27, thereby promoting protein folding capacity and improving proteome stability under stress conditions. ML346 has been shown to restore protein folding and reduce misfolded protein burden in models of conformational diseases, highlighting its relevance for studying mechanisms underlying protein aggregation and cellular stress adaptation. Its activity toward Hsp70 is reported in the low micromolar range, supporting its utility as a pharmacological probe for investigating chaperone-mediated pathways and HSF-1 signaling. Notably, ML346 demonstrates minimal cytotoxicity and maintains functional specificity in cellular systems, making it suitable for use in mechanistic studies and screening platforms aimed at identifying modulators of proteostasis networks. Experimental applications typically involve concentration ranges optimized according to specific cell-based assays or disease models, particularly in studies of neurodegeneration, protein misfolding disorders, and stress response regulation.