Oligonucleotide conjugate GRN163L targeting human telomerase as potential anticancer and antimetastatic agent.
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.
Gryaznov
Sergei M
SM
Geron Corporation, 230 Constitution Drive, Menlo Park, CA 94025, USA. sgryaznov@geron.com
Jackson
Shalmica
S
Dikmen
Gunnur
G
Harley
Calvin
C
Herbert
Brittney-Shea
BS
Wright
Woodring E
WE
Shay
Jerry W
JW
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
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C505952:GRN163L peptide; D009841:Oligonucleotides; D009842:Oligopeptides; D019098:Telomerase