Thapsigargin

Thapsigargin is a tight-binding inhibitor of a class of enzymes known by the acronym SERCA, which stands for sarco / endoplasmic reticulum Ca 2+ ATPase. Structurally, thapsigargin is classified as a sesquiterpene lactone, and is extracted from a plant, Thapsia garganica. It is a tumor promoter in mammalian cells. The structural similarity of thapsigargin with the anti-malarial drug, artemesinin, led to a proposal that this class of drugs acts on SERCA within the malaria parasite (for example, the human malaria parasite, Plasmodium falciparum).

Thapsigargin raises cytosolic calcium concentration by (1) blocking the ability of the cell to pump calcium into the sarcoplasmic and endoplasmic reticula, (2) opening IP3-gated channels in the endoplasmic reticulum (ER), and (3) activating plasma membrane calcium channels, allowing an influx of calcium to the cytosol.

Thapsigargin, along with ATP, is useful in experimentation examining the impacts of increasing cytosolic calcium concentrations. Such compounds are known as calcium agonists due to their ability to increase cellular concentrations of calcium.

Potential medical uses of Thapsigargin

Thapsigagrin is mentioned as a possible treatment for cataract.