The
sesquiterpene lactone thapsigargin is found in the plant Thapsia garganica L., and is one of the major constituents of the roots and fruits of this Mediterranean species. In 1978, the first pharmacological effects of
thapsigargin were established and the full structure was elucidated in 1985. Shortly after, the overall mechanism of the
Sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) inhibition that leads to apoptosis was discovered.
Thapsigargin has a potent antagonistic effect on the SERCA and is widely used to study Ca2+-signaling. The effect on SERCA has also been utilized in the treatment of solid
tumors. A
prodrug has been designed to target the blood vessels of
cancer cells; the death of these blood vessels then leads to
tumor necrosis. The first clinical trials of this
drug were initiated in 2008, and the potent
drug is expected to enter the market in the near future under the generic name Mipsagargin (G-202). This review will describe the discovery of the new
drug, the on-going elucidation of the biosynthesis of
thapsigargin in the plant and attempts to supply the global market with a novel potent anti-
cancer drug.