title: Telomerase inhibitors--oligonucleotide phosphoramidates as potential therapeutic agents.
abstract: We have designed, synthesized, and evaluated using physical, chemical and biochemical assays various oligonucleotide N3'-->P5' phosphoramidates, as potential telomerase inhibitors. Among the prepared compounds were 2'-deoxy, 2'-hydroxy, 2'-methoxy, 2'-ribo-fluoro, and 2'-arabino-fluoro oligonucleotide phosphoramidates, as well as novel N3'-->P5' thio-phosphoramidates. The compounds demonstrated sequence specific and dose dependent activity with IC50 values in the sub-nM to pM concentration range.
authors.affiliation: Geron Corporation, 230 Constitution Drive, Menlo Park, California 94025, USA.
authors.forename: S
authors.initials: S
authors.lastname: Gryaznov
authors.forename: K
authors.initials: K
authors.lastname: Pongracz
authors.forename: T
authors.initials: T
authors.lastname: Matray
authors.forename: R
authors.initials: R
authors.lastname: Schultz
authors.forename: R
authors.initials: R
authors.lastname: Pruzan
authors.forename: J
authors.initials: J
authors.lastname: Aimi
authors.forename: A
authors.initials: A
authors.lastname: Chin
authors.forename: C
authors.initials: C
authors.lastname: Harley
authors.forename: B
authors.initials: B
authors.lastname: Shea-Herbert
authors.forename: J
authors.initials: J
authors.lastname: Shay
authors.forename: Y
authors.initials: Y
authors.lastname: Oshima
authors.forename: A
authors.initials: A
authors.lastname: Asai
authors.forename: Y
authors.initials: Y
authors.lastname: Yamashita
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010756:Phosphoric Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D019098:Telomerase / Q000037:antagonists & inhibitors*
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D009841:Oligonucleotides; D010756:Phosphoric Acids; C011067:phosphoramidic acid; D019098:Telomerase