Sarco/Endoplasmic Reticulum Calcium ATPase Inhibitors: Beyond Anticancer Perspective

The
sarco/endoplasmic reticulum calcium ATPase (SERCA), which plays
a key role in the maintenance of Ca2+ ion homeostasis,
is an extensively studied enzyme, the inhibition of which has a considerable
impact on cell life and death decision. To date, several SERCA inhibitors
have been thoroughly studied and the most notable one, a derivative
of the sesquiterpene lactone thapsigargin, is gradually approaching
a clinical application. Meanwhile, new compounds with SERCA-inhibiting
properties of natural, synthetic, or semisynthetic origin are being
discovered and/or developed; some of these might also be suitable
for the development of new drugs with improved performance. This review
brings an up-to-date comprehensive overview of recently discovered
compounds with the potential of SERCA inhibition, discusses their
mechanism of action, and highlights their potential clinical applications,
such as cancer treatment.