Thapsigargin (TPG)

Thapsigargin is non-competitive inhibitor of a class of enzymes known by the acronym SERCA, which stands for sarco / endoplasmic reticulum Ca2+ 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 anti-malarial drug artemisinin is also a sesquiterpene lactone, leading to a proposal that this class of drugs works by inhibiting the SERCA of malaria parasites such as Plasmodium falciparum;[3][4] this hypothesis awaits confirmation. Thapsigargin raises cytosolic (intracellular) calcium concentration by blocking the ability of the cell to pump calcium into the sarcoplasmic and endoplasmic reticula which causes these stores to become depleted. Store-depletion can secondarily activate plasma membrane calcium channels, allowing an influx of calcium into the cytosol.