Heat shock proteins (HSPs) are a family of proteins produced by cells in response to exposure to stress conditions. Besides, HSPs are a large class of molecular chaperones. It plays a role in protein maturation, refolding, and degradation. Moreover, HSPs may promote or inhibit neural development by regulating cell differentiation, neurite growth, cell migration, or angiogenesis. GRP94 is an Hsp90-like protein in the endoplasmic reticulum cavity. So it is a partner of secretory proteins and membrane proteins. GRP94 maintains ER protein folding ability, maintains ER pressure sensor, and inhibits ER-related Pro apoptotic mechanisms. It plays a key role in regulating the balance between survival and death of cancer cells. Furthermore, GRP94 is induced by the accumulation of misfolded proteins and binds and hydrolyzes ATP.

Meanwhile, GRP94 is a key partner of many toll-like receptors (TLRs) and integrins. And it has related to the unfolded protein response (UPR). Nonetheless, GRP94 is essential for the maturation of membrane resident and secretory protein clients. Elevated GRP94 expression is relevant to aggressive phenotypes and adverse clinical outcomes in a variety of cancers. Inhibition of GRP94 offers the prospect of disrupting several key cancer pathways, including cell proliferation, immunosuppression, and inflammation. Therefore, GRP94 is a potential molecular marker and therapeutic target for malignant tumors. Today, we will introduce a Grp94-selective inhibitor, PU-H54.

PU-H54, a Grp94-selective inhibitor, Can be Used for the Research of Breast Cancer.

First of all, PU-H54, a Grp94-selective inhibitor, has the potential for research on breast cancer. In particular, the Hsp90 chaperone family, comprised of humans of four paralogs, Hsp90α, Hsp90β, Grp94, and Trap-1. It has an important role in malignancy.

In the second place, PU-H54 is a purine-based (PU) Grp94-selective inhibitor. Additionally, PU-H54 has a lower affinity for Hsp90α and Hsp90β.

All in all, PU-H54, as a Grp94-selective inhibitor, has the potential for breast research.


Pallav D Patel, et al. Nat Chem Biol. 2013 Nov;9(11):677-84.