Selective, potent blockade of the IRE1 and ATF6 pathways by 4-phenylbutyric acid analogues.

Background And Purpose: 4-Phenylbutyric acid (4-PBA) is a chemical chaperone that eliminates the accumulation of unfolded proteins in the endoplasmic reticulum (ER). However, its chaperoning ability is often weak and unable to attenuate the unfolded protein response (UPR) in vitro or in vivo. To develop more potent chemical chaperones, we synthesized six analogues of 4-PBA and evaluated their pharmacological actions on the UPR.

Intervention in genotoxic stress-induced senescence by cordycepin through activation of eIF2α and suppression of Sp1.

In this study, we show that cordycepin (3'-deoxyadenosine), a major nucleoside isolated from Cordyceps species, attenuates genotoxic stress-induced senescence. Etoposide- or doxorubicin-treated cells exhibited senescent morphology, growth arrest, and positive staining for senescence-associated β-galactosidase. The induction of the senescent phenotype was inhibited by the treatment of cordycepin.