ML346

ML346 is an activator of Hsp70, with an EC ₅₀ of 4600 nM in HeLa cells. ML346 (10 μM) restores proteostasis, restores CFTR-mediated iodide conductance, and enhances the correct folding of proteins expressed in two different cellular compartments. ML346 (Compound F1) induces multiple responses and strongly induces Hsp70, the oxidative stress response genes (HO1 and GCLM), and a 2.5-fold upregulation of BiP in WT MEF cells. ML346 (0.5-25 μM) exhibits cytoprotective effects in cells after a 35 min severe heat shock, and also causes a two-fold protection from H ₂ O ₂ -induced apoptosis.

ML346 suppress the aggregation of polyQ35 in a C. elegans model, suggesting the probe has efficacy in modifying protein aggregation and associated toxicity.