title: Oligonucleotide conjugate GRN163L targeting human telomerase as potential anticancer and antimetastatic agent.
abstract: Telomerase is one of the key enzymes responsible for the proliferative immortality of the majority of cancer cells. We recently introduced a new telomerase inhibitor, a 13-mer oligonucleotide N3' --> P5'-thio-phosphoramidate lipid conjugate, designated as GRN163L. This compound inhibits telomerase activity in various tumor cell lines with IC(50) values of 3-300 nM without any cellular uptake enhancers. GRN163L demonstrated potent and sequence specific anti-cancer activity in vivo in multiple animal models. This compound was able to significantly affect not only the growth of primary tumors, but also the spread and proliferation of metastases. GRN163L is currently in Phase I and Phase I/II clinical studies in patients with solid tumors and CLL, respectively.
authors: Geron Corporation, 230 Constitution Drive, Menlo Park, CA 94025, USA. sgryaznov@geron.com
authors: Sergei M
authors: SM
authors: Gryaznov
authors: Shalmica
authors: S
authors: Jackson
authors: Gunnur
authors: G
authors: Dikmen
authors: Calvin
authors: C
authors: Harley
authors: Brittney-Shea
authors: BS
authors: Herbert
authors: Woodring E
authors: WE
authors: Wright
authors: Jerry W
authors: JW
authors: Shay
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D051379:Mice; D009841:Oligonucleotides; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D019098:Telomerase / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C505952:GRN163L peptide; D009841:Oligonucleotides; D009842:Oligopeptides; D019098:Telomerase