HSF1 Activators

HSF1 activators are a class of chemicals characterized by their ability to either directly stimulate HSF1 or induce cellular conditions that lead to HSF1 activation. Celastrol and arsenite, for instance, cause cellular stress that directly leads to HSF1 activation. On the other hand, chemicals like Geldanamycin and 17-AAG function as inhibitors of Hsp90, a chaperone protein that normally keeps HSF1 in an inactive state. By inhibiting Hsp90, these chemicals liberate HSF1, enabling its activation and subsequent triggering of the heat shock response. Yet another mode of action is the induction of proteotoxic stress, as evidenced by triptolide and MG132, which leads to protein misfolding and aggregation, thereby necessitating the activation of HSF1 for cellular recovery.

Quercetin and epigallocatechin activate HSF1 through the induction of cellular stress and oxidative stress, respectively. KNK437 interestingly blocks heat shock protein synthesis, thereby indirectly promoting HSF1 activation as a compensatory cellular response. Lastly, 2-Deoxy-D-glucose and Tunicamycin act by causing metabolic and endoplasmic stress, respectively. These stresses can activate HSF1 through various signaling pathways such as AMPK for 2-Deoxy-D-glucose and PERK for Tunicamycin.