Targeting thapsigargin towards tumors

•We review isolation and structural elucidation of thapsigargin.•We review medicinal chemistry of thapsigargin.•We review the effect of thapsigargin on the SERCA pump.•We review the development of a prodrug of thapsigargin.•We review the clinical trials performed on the prodrug of thapsigargin. The skin irritating principle from Thapsia garganica was isolated, named thapsigargin and the structure elucidated. By inhibiting the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) thapsigargin provokes apoptosis in almost all cells. By conjugating thapsigargin to peptides, which are only substrates for either prostate specific antigen (PSA) or prostate specific membrane antigen (PSMA) prodrugs were created, which selectively affect prostate cancer cells or neovascular tissue in tumors. One of the prodrug is currently tested in clinical phase II. The prodrug under clinical trial has been named mipsagargin.