#8591. From Plant to Patient: Thapsigargin, a Tool for Understanding Natural Product Chemistry, Total Syntheses, Biosynthesis, Taxonomy, ATPases, Cell Death, and Drug Development

January 2027publication date
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Journal’s subject area:
Medicine (all);
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Abstract:
Mipsagargin, the thapsigargin prodrug, was developed in order to obtain a drug for treatment of cancer diseases characterized by the presence of prostate specific membrane antigen (PSMA) in the neovascular tissue of the tumors. Even though mipsagargin showed interesting clinical effects the results did not encourage funding and consequently the attempt to register the drug has been abandoned. In spite of this disappointing fact, the research performed to develop the drug has resulted in important scientific discoveries concerning the chemistry, biosynthesis and biochemistry of sesquiterpene lactones, the mechanism of action of ATPases, mechanisms for cell death caused by the unfolded protein response, and the use of prodrugs for cancer-targeting cytotoxins.
Keywords:
Apoptosis; Drug development; Mipsagargin; Sarco-endoplasmic reticulum calcium ATPase; Targeted prodrugs; Thapsigargin

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