title: Targeting thapsigargin towards tumors.
abstract: The skin irritating principle from Thapsia garganica was isolated, named thapsigargin and the structure elucidated. By inhibiting the sarco/endoplasmic reticulum Ca(2+) 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.
authors: Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen Ø, Denmark.
authors: Nhu Thi Quynh
authors: NT
authors: Doan
authors: Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen Ø, Denmark.
authors: Eleonora Sandholdt
authors: ES
authors: Paulsen
authors: Department of Biomedicine, Ole Worms Allé 6, Aarhus University, DK-8000 Aarhus C, Denmark.
authors: Pankaj
authors: P
authors: Sehgal
authors: Department of Biomedicine, Ole Worms Allé 6, Aarhus University, DK-8000 Aarhus C, Denmark.
authors: Jesper Vuust
authors: JV
authors: Møller
authors: Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10, DK-8000 Aarhus C, Denmark.
authors: Poul
authors: P
authors: Nissen
authors: The Bunting-Blaustein Cancer Research Building, 1650 Orleans Street, Baltimore, MD 21231, USA.
authors: Samuel R
authors: SR
authors: Denmeade
authors: The Bunting-Blaustein Cancer Research Building, 1650 Orleans Street, Baltimore, MD 21231, USA.
authors: John T
authors: JT
authors: Isaacs
authors: GenSpera, 2511 N Loop 1604 W, Suite 204, San Antonio, TX 78258, USA.
authors: Craig A
authors: CA
authors: Dionne
authors: Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen Ø, Denmark. Electronic address: soren.christensen@sund.ku.dk.
authors: Søren Brøgger
authors: SB
authors: Christensen
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019661:Apiaceae / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D011355:Prodrugs / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019284:Thapsigargin / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D011355:Prodrugs; D019284:Thapsigargin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
keywords: Prodrug; Prostate specific antigen (PSA); Prostate specific membrane antigen (PSMA); Sarco/endoplasmic reticulum (SERCA); Targeting drugs; Thapsigargin