HSP 40 Activators

The chemical class of HSP 40 activators encompasses a diverse array of compounds that can modulate the activity of Heat Shock Protein 40 (HSP40), a key molecular chaperone involved in protein folding and cellular proteostasis. Geldanamycin and 17-AAG are HSP90 inhibitors that indirectly activate HSP40 by disrupting the HSP90-HSP70-HSP40 chaperone complex, leading to increased client protein binding to HSP70 and HSP40 and activating the heat shock response. Natural compounds like quercetin, withaferin A, celastrol, resveratrol, and epigallocatechin gallate (EGCG) indirectly activate HSP40 by modulating cellular stress response pathways, enhancing the expression and function of HSP40. These compounds, through their antioxidant and anti-inflammatory properties, contribute to the maintenance of protein homeostasis and cellular proteostasis.

Proteasome inhibitor MG-132 indirectly influences HSP40 by promoting the accumulation of misfolded proteins, leading to the upregulation of heat shock proteins, including HSP40, for the clearance and refolding of misfolded proteins. Radicicol, another HSP90 inhibitor, disrupts the HSP90-HSP70-HSP40 chaperone complex, activating the heat shock response and promoting cellular protein homeostasis. 15d-PGJ2, a natural prostaglandin, modulates cellular stress response pathways, leading to the upregulation of HSP40 and supporting cellular proteostasis in response to various stressors. Pifithrin-μ indirectly activates HSP40 by inhibiting the interaction between p53 and HSP70, enhancing the chaperone function of HSP70 in collaboration with HSP40.