title: Parthenolide prodrug LC-1 slows growth of intracranial glioma.
abstract: LC-1 (also known as DMAPT or dimethylamino-parthenolide), a prodrug of parthenolide, was tested for anti-proliferative activity against glioma. LC-1 was found to have low micromolar cytotoxic activity against three glioma cell lines and was also found to be brain penetrant in healthy mice (2.1-3.0 brain-to-plasma ratio). In a syngeneic GL261 murine glioma model, LC-1 slowed tumor growth kinetics and extended the survival time of tumor-bearing mice in comparison to the vehicle control. Consequently, LC-1 represents a promising lead compound for further development as a glioma therapy.
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Hexum
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Chani M
authors.initials: CM
authors.lastname: Becker
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Kempema
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Ohlfest
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Largaespada
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: daharki@umn.edu.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Harki
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005910:Glioma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D006207:Half-Life; D053208:Kaplan-Meier Estimate; D051379:Mice; D011355:Prodrugs / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D012717:Sesquiterpenes / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: C524858:LC-1 compound; D011355:Prodrugs; D012717:Sesquiterpenes; C002669:parthenolide
keywords: Blood–brain barrier; Glioblastoma; LC-1; Parthenolide; Pharmacokinetics