Sarcoendoplasmic reticulum calcium ATPase (SERCA) is a critical intracellular regulator of Ca+2 which is important for precise protein folding. Perturbation of intracellular Ca+2 can enhance protein misfolding and is upregulated in cancers. To accommodate protein misfolding, cancer cells upregulate unfolded protein response (UPR). Although this is a cancer adaptive mechanism, when UPR exceeds a certain threshold, it also activates pro-apoptotic mechanisms. We have developed a novel anti-cancer compound, C1, a bioavailable specific inhibitor of SERCA2 that is able to selectively inhibit triple negative breast cancer (TNBC) in vitro and in vivo using a xenograft model. C1 also served as a platform for the optimization us and development of more effective compounds.
Understand the scope of Unfolded Protein Response Pathway (UPR).
C1 ability to induce UPR.
C1 analogs improved accumulation and molecular activity in triple negative breast cancer cell line.