| GRN163 FIGHT AGAINST CANCERS |
| The basic requirement for an anti-cancer drug to be effective with minimal side effects is target-specific, i.e. "working on cancer cell only" |
It is known that a key characteristic of malignant cancer cells is their
immortality or limitless replication potential. And, it has been observed
that cell replication is associated with the maintenance of telomeres.
And in most cases, the maintenance of telomeres is through the
reactivation of the reverse transcriptase telomerase. Because of need
of this activity, telomerase is usually and constitutively over-expressed
in most cancer cells. Comparing to the normal cells, telomeres are also
critically short in most cancer cells. Consequently, researchers use
these differences including the direct targeting of the
telomere/telomerase machinery components for the anticancer
therapeutic strategy. As mentioned before, the basic components of
telomerase targeted by the anti-cancer drugs are the protein
component hTERT or RNA component hTR.
Examples of such agents are GRN163L and BRACO19. BRAC019 is a
telomere targeting-agent (TTA), to target the telomere itself. GRN163L
is a thio-phosphoramidate oligonucleotide targeting the template
region of hTR as a "template antagonist. Anti-tumour effects have
been observed for GRN163L, in xenografted human tumours in mice.
However, its effects are largely dependent upon initial telomere length.
[1]
Researchers from University of Texas Southwestern Medical Center
found that a lipid-modified N3'-->P5' thio-phosphoramidate
oligonucleotide (GRN163L) inhibits telomerase more potently than its
parental nonconjugated thio-phosphoramidate sequence (GRN163).
[2] In another study, German researchers compared the potential of
GRN163 and GRN163L for the treatment of human hepatoma
xenografts (Hep3B and Huh7) in nude mice. The study indicated that
both GRN163 and GRN163L inhibited telomerase activity and tumor
cell growth in a dose-dependent manner in vitro and in vivo. However,
the potency and efficacy of GRN163L, was superior to GRN163. [3]
A recent study has shown that GRN163L stopped the spread of cancer
into the lungs of the mice. Thus, it might be able to prevent metastasis
in other tumors. Currently, the innovator company, Geron, considers
its application in chronic lymphocytic leukemia.
HOME
REFERENCES
[1] Kelland LR Overcoming the immortality of tumour cells by telomere
and telomerase based cancer therapeutics--current status and future
prospects. Eur J Cancer. 2005 May;41(7):971-9. [2] Herbert BS et al,
Lipid modification of GRN163, an N3'-->P5' thio-phosphoramidate
oligonucleotide, enhances the potency of telomerase inhibition.
Oncogene. 2005 Aug 4;24(33):5262-8. [3] Djojosubroto MW et al,
Telomerase antagonists GRN163 and GRN163L inhibit tumor growth
and increase chemosensitivity of human hepatoma. Hepatology. 2005
Aug 19; [4] New Molecule Stops Cancer's Spread, HealthDay,
September 2, 2005
ALL RIGHTS RESERVED 2006 zhion.
immortality or limitless replication potential. And, it has been observed
that cell replication is associated with the maintenance of telomeres.
And in most cases, the maintenance of telomeres is through the
reactivation of the reverse transcriptase telomerase. Because of need
of this activity, telomerase is usually and constitutively over-expressed
in most cancer cells. Comparing to the normal cells, telomeres are also
critically short in most cancer cells. Consequently, researchers use
these differences including the direct targeting of the
telomere/telomerase machinery components for the anticancer
therapeutic strategy. As mentioned before, the basic components of
telomerase targeted by the anti-cancer drugs are the protein
component hTERT or RNA component hTR.
Examples of such agents are GRN163L and BRACO19. BRAC019 is a
telomere targeting-agent (TTA), to target the telomere itself. GRN163L
is a thio-phosphoramidate oligonucleotide targeting the template
region of hTR as a "template antagonist. Anti-tumour effects have
been observed for GRN163L, in xenografted human tumours in mice.
However, its effects are largely dependent upon initial telomere length.
[1]
Researchers from University of Texas Southwestern Medical Center
found that a lipid-modified N3'-->P5' thio-phosphoramidate
oligonucleotide (GRN163L) inhibits telomerase more potently than its
parental nonconjugated thio-phosphoramidate sequence (GRN163).
[2] In another study, German researchers compared the potential of
GRN163 and GRN163L for the treatment of human hepatoma
xenografts (Hep3B and Huh7) in nude mice. The study indicated that
both GRN163 and GRN163L inhibited telomerase activity and tumor
cell growth in a dose-dependent manner in vitro and in vivo. However,
the potency and efficacy of GRN163L, was superior to GRN163. [3]
A recent study has shown that GRN163L stopped the spread of cancer
into the lungs of the mice. Thus, it might be able to prevent metastasis
in other tumors. Currently, the innovator company, Geron, considers
its application in chronic lymphocytic leukemia.
HOME
REFERENCES
[1] Kelland LR Overcoming the immortality of tumour cells by telomere
and telomerase based cancer therapeutics--current status and future
prospects. Eur J Cancer. 2005 May;41(7):971-9. [2] Herbert BS et al,
Lipid modification of GRN163, an N3'-->P5' thio-phosphoramidate
oligonucleotide, enhances the potency of telomerase inhibition.
Oncogene. 2005 Aug 4;24(33):5262-8. [3] Djojosubroto MW et al,
Telomerase antagonists GRN163 and GRN163L inhibit tumor growth
and increase chemosensitivity of human hepatoma. Hepatology. 2005
Aug 19; [4] New Molecule Stops Cancer's Spread, HealthDay,
September 2, 2005
ALL RIGHTS RESERVED 2006 zhion.
PHARMCEUTICAL
INDUSTRY
Foundamental
Science
Colloidal
Stabilization
Drug Product
Development
Patent Application
Product
Development
Product
Ingredients
Colorant
Scale up a batch 1
Drug Delivery
Industry
Drug Delivery -
Smart Bomb
Lotion, Cream,
Preps
Enteric
Coating-Eudragit
Enteric
Coating-Nutrateric
SR
Coating-Aquacoat
Drug Industry
Drug
Competitions
Drug in
Development
Cholesterol-lowering
Drug-Terminologies
Packaging
Materials
Market
Drug Dev- 2004
Drug Dev -
2005Q1
Drug Dev- 2005Q2
Drug
Dev-2005Summer
Drug Dev-2005Q3
Orphan Drug
Protein Drug
Niche Market
Novo Norkdisk
R&D
Equipment
Blenders
CONTRACT
MANUFACT.
Nutrition
Supplements
NEW DRUGS
Arranon
Actoplus Met
Alfuzosin
Ambien CR
Avastin
Asmanex(R)
Erbitux
(cetuximab)
Gardasil
GRN163
Herceptin
Increlex (rhIGF-1)
Lidoerm
(Lidocaine)
Liraglutide
Lyrica (pregabalin)
Rozerem
Sorafenib
Sutent
Tamsulosin
Torcetrapib
Zometa
OLD DRUGS
Lithium Carbonate
DRUG NOTES
[CONSTRUCT]
Clinical Research
Terminologies
FDA ALERTS
Protein Drug
Market
Niche Market
Orphan Drug
levothyroxine
Protein Drug 1
Protein Drug2
Double-blind
Study
INDUSTRY
Foundamental
Science
Colloidal
Stabilization
Drug Product
Development
Patent Application
Product
Development
Product
Ingredients
Colorant
Scale up a batch 1
Drug Delivery
Industry
Drug Delivery -
Smart Bomb
Lotion, Cream,
Preps
Enteric
Coating-Eudragit
Enteric
Coating-Nutrateric
SR
Coating-Aquacoat
Drug Industry
Drug
Competitions
Drug in
Development
Cholesterol-lowering
Drug-Terminologies
Packaging
Materials
Market
Drug Dev- 2004
Drug Dev -
2005Q1
Drug Dev- 2005Q2
Drug
Dev-2005Summer
Drug Dev-2005Q3
Orphan Drug
Protein Drug
Niche Market
Novo Norkdisk
R&D
Equipment
Blenders
CONTRACT
MANUFACT.
Nutrition
Supplements
NEW DRUGS
Arranon
Actoplus Met
Alfuzosin
Ambien CR
Avastin
Asmanex(R)
Erbitux
(cetuximab)
Gardasil
GRN163
Herceptin
Increlex (rhIGF-1)
Lidoerm
(Lidocaine)
Liraglutide
Lyrica (pregabalin)
Rozerem
Sorafenib
Sutent
Tamsulosin
Torcetrapib
Zometa
OLD DRUGS
Lithium Carbonate
DRUG NOTES
[CONSTRUCT]
Clinical Research
Terminologies
FDA ALERTS
Protein Drug
Market
Niche Market
Orphan Drug
levothyroxine
Protein Drug 1
Protein Drug2
Double-blind
Study
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