ML346 is an activator for both Hsp70 expression and HSF-1 activity, achieving an EC50 value of 4.6 μM specifically for Hsp70. It has demonstrated the ability to aid in protein folding within models of conformational diseases, doing so without significant cytotoxic effects or a loss of specificity. ML346 notably causes increases in certain genes and proteins that are part of the heat shock response (HSR), including chaperones like Hsp70, Hsp40, and Hsp27[1].
体内研究
Additionally, ML346 has been shown to prevent the aggregation of polyQ35 in a C. elegans model, indicating its potential effectiveness in altering protein aggregation and the toxicity associated with it[1].
体外研究
With an EC50 of 4600 nM in HeLa cells, ML346 stands out as a potent activator of Hsp70. At a concentration of 10 μM, ML346 is capable of restoring proteostasis, enhancing CFTR-mediated iodide conductance, and improving the proper folding of proteins located in two distinct cellular compartments[1].
ML346 triggers a variety of responses, prominently inducing Hsp70, oxidative stress response genes such as HO1 and GCLM, and a 2.5-fold increase in BiP expression in WT MEF cells. Ranging from 0.5 to 25 μM, ML346 provides cytoprotective effects to cells following a severe 35-minute heat shock and offers two-fold protection against apoptosis induced by H2O2[2].
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