title: The practical synthesis of a novel and highly potent analogue of bryostatin.
abstract: Macrocycle 1 is a new highly potent analogue of bryostatin 1, a promising anti-cancer agent currently in human clinical trials. In vitro, 1 displays picomolar affinity for PKC and exhibits over 100-fold greater potency than bryostatin 1 when tested against various human cancer cell lines. Macrocycle 1 can be generated in clinically required amounts by chemical synthesis in only 19 steps (LLS) and represents a new clinical lead for the treatment of cancer.
authors.affiliation: Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA. wenderp@stanford.edu
authors.forename: Paul A
authors.initials: PA
authors.lastname: Wender
authors.forename: Jeremy L
authors.initials: JL
authors.lastname: Baryza
authors.forename: Chad E
authors.initials: CE
authors.lastname: Bennett
authors.forename: F Christopher
authors.initials: FC
authors.lastname: Bi
authors.forename: Stacey E
authors.initials: SE
authors.lastname: Brenner
authors.forename: Michael O
authors.initials: MO
authors.lastname: Clarke
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Horan
authors.forename: Cindy
authors.initials: C
authors.lastname: Kan
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Lacôte
authors.forename: Blaise
authors.initials: B
authors.lastname: Lippa
authors.forename: Peter G
authors.initials: PG
authors.lastname: Nell
authors.forename: Tim M
authors.initials: TM
authors.lastname: Turner
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D054713:Bryostatins; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D018942:Macrolides; D011493:Protein Kinase C / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D054713:Bryostatins; D007783:Lactones; D018942:Macrolides; C046785:bryostatin 1; D011493:Protein Kinase C