Oligonucleotide conjugate GRN163L targeting human telomerase as potential anticancer and antimetastatic agent

Sergei M. Gryaznov; Shalmica Jackson; Gunnur Dikmen; Calvin Harley; Brittney Shea Herbert; Woodring E. Wright; Jerry W. Shay

doi:10.1080/15257770701547271

Oligonucleotide conjugate GRN163L targeting human telomerase as potential anticancer and antimetastatic agent

Sergei M. Gryaznov, Shalmica Jackson, Gunnur Dikmen, Calvin Harley, Brittney Shea Herbert, Woodring E. Wright, Jerry W. Shay

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

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 IC50 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.

Original language	English (US)
Pages (from-to)	1577-1579
Number of pages	3
Journal	Nucleosides, Nucleotides and Nucleic Acids
Volume	26
Issue number	10-12
DOIs	https://doi.org/10.1080/15257770701547271
State	Published - Oct 2007

Keywords

Adhesion
Anticancer
GRN163L
Morphology
Phosphoramidates
Telomerase

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Genetics

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10.1080/15257770701547271

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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 IC50 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.",

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AU - Gryaznov, Sergei M.

AU - Jackson, Shalmica

AU - Dikmen, Gunnur

AU - Harley, Calvin

AU - Herbert, Brittney Shea

AU - Wright, Woodring E.

AU - Shay, Jerry W.

PY - 2007/10

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AB - 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 IC50 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.

KW - Adhesion

KW - Anticancer

KW - GRN163L

KW - Morphology

KW - Phosphoramidates

KW - Telomerase

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Oligonucleotide conjugate GRN163L targeting human telomerase as potential anticancer and antimetastatic agent

Abstract

Keywords

ASJC Scopus subject areas

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