GRP78 Selective Inhibitors From a Direct‐to‐Biology Strategy

Because cancer cells have heightened protein homeostasis (proteostasis) requirements, there is interest in targeting proteostasis machinery, including the 70 kDa heat shock proteins (HSP70s), as potential cancer therapeutics. However, studies have shown that the HSP70 family is differentially regulated across cancers, and global targeting may produce unwanted toxicities. For this reason, our lab has focused on isoform-selective targeting of HSP70s, including the endoplasmic reticulum-resident HS