Phenylhydrazone-based endoplasmic reticulum proteostasis regulator compounds with enhanced biological activity.

ABSTRACT: Pharmacological enhancement of endoplasmic reticulum (ER) proteostasis is an attractive strategy to mitigate pathology linked to etiologically diverse protein misfolding diseases. However, despite this promise, few compounds have been identified that enhance ER proteostasis through defined mechanisms of action. We previously identified the phenylhydrazone-based compound AA263 as a molecule that promotes adaptive ER proteostasis remodeling through mechanisms including preferential activation of the ATF6 signaling arm of the unfolded protein response (Plate et al., 2016). However, the protein target(s) of AA263 and the potential for further development of this class of ER proteostasis regulators had not been previously explored. Here, we employ chemical proteomics to demonstrate that AA263 c

SUBMITTER: Kline GM 

PROVIDER: S-EPMC12834500 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature