Identification

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Name
Grn163l
Accession Number
DB05036
Type
Small Molecule
Groups
Investigational
Description

GRN163L is a novel anti-cancer drug. It has been characterized preclinically and shown to inhibit telomerase in human tumor cells of many cancer types (including lung, breast, prostate, liver, and early stage of human breast cancer), in both cell culture systems and animal models. Study of this drug shows the its potential utility in the treatment of patients with hematologic and solid tumor malignancies.

Synonyms
Not Available
Categories
Not Available
UNII
Not Available
CAS number
Not Available
Weight
Not Available
Chemical Formula
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

Pharmacology

Indication

Investigated for use/treatment in leukemia (lymphoid) and solid tumors.

Pharmacodynamics
Not Available
Mechanism of action

GRN163L has been characterized preclinically and shown to inhibit telomerase in human tumor cells of many cancer types. It targets the template region, or active site, of telomerase. GRN163L does not exhibit antisense activity (binding to messenger RNA), but rather directly bind to the RNA component of telomerase at the active site of the enzyme, thereby acting like a conventional pharmaceutical drug. Inhibiting telomerase activity should result in telomere shortening and therefore cause aging and death of cancer cells.

TargetActionsOrganism
UTelomerase-binding protein EST1ANot AvailableHumans
UN-terminal kinase-like proteinNot AvailableHumans
UProstaglandin E synthase 3Not AvailableHumans
UTelomerase reverse transcriptaseNot AvailableHumans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Gryaznov SM, Jackson S, Dikmen G, Harley C, Herbert BS, Wright WE, Shay JW: Oligonucleotide conjugate GRN163L targeting human telomerase as potential anticancer and antimetastatic agent. Nucleosides Nucleotides Nucleic Acids. 2007;26(10-12):1577-9. [PubMed:18066830]
  2. Gomez-Millan J, Goldblatt EM, Gryaznov SM, Mendonca MS, Herbert BS: Specific telomere dysfunction induced by GRN163L increases radiation sensitivity in breast cancer cells. Int J Radiat Oncol Biol Phys. 2007 Mar 1;67(3):897-905. Epub 2006 Dec 15. [PubMed:17175117]
  3. Hochreiter AE, Xiao H, Goldblatt EM, Gryaznov SM, Miller KD, Badve S, Sledge GW, Herbert BS: Telomerase template antagonist GRN163L disrupts telomere maintenance, tumor growth, and metastasis of breast cancer. Clin Cancer Res. 2006 May 15;12(10):3184-92. [PubMed:16707619]
  4. Gellert GC, Dikmen ZG, Wright WE, Gryaznov S, Shay JW: Effects of a novel telomerase inhibitor, GRN163L, in human breast cancer. Breast Cancer Res Treat. 2006 Mar;96(1):73-81. Epub 2005 Dec 1. [PubMed:16319992]
  5. Dikmen ZG, Gellert GC, Jackson S, Gryaznov S, Tressler R, Dogan P, Wright WE, Shay JW: In vivo inhibition of lung cancer by GRN163L: a novel human telomerase inhibitor. Cancer Res. 2005 Sep 1;65(17):7866-73. [PubMed:16140956]
External Links
PubChem Substance
347909904

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableMultiple Myeloma (MM)1
1CompletedTreatmentCancer, Breast1
1CompletedTreatmentChronic Lymphoproliferative Diseases1
1CompletedTreatmentLung Cancers1
1CompletedTreatmentMultiple Myeloma (MM)1
1CompletedTreatmentSolid Tumor Malignancies1
2CompletedTreatmentLocally Recurrent or Metastatic Breast Cancer1
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2CompletedTreatmentMultiple Myeloma (MM)1
2CompletedTreatmentMyeloid Malignancy / Primary Myelofibrosis / Secondary Myelofibrosis1
2TerminatedTreatmentAnaplastic Astrocytoma (AA) / Anaplastic Ependymoma / Astrocytoma, Grade II / Brainstem Tumors / Ependymomas / Giant Cell Glioblastoma / Glioblastomas / Gliosarcoma / Oligodendrogliomas1
2WithdrawnTreatmentChildhood Hepatoblastoma / Hepatoblastomas / Previously Treated Childhood Rhabdomyosarcoma / Recurrent Childhood Liver Cancer / Recurrent Childhood Rhabdomyosarcoma / Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Recurrent Neuroblastoma / Recurrent Osteosarcoma / Rhabdomyosarcomas1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
Not Available
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Telomeric dna binding
Specific Function
Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini. May have a general role in telomere regulation. Promotes in vitro the abilit...
Gene Name
SMG6
Uniprot ID
Q86US8
Uniprot Name
Telomerase-binding protein EST1A
Molecular Weight
160460.34 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Protein tyrosine kinase activity
Specific Function
Regulates COPI-mediated retrograde traffic. Has no detectable kinase activity in vitro.Isoform 6 acts as transcriptional activator. It binds to three different types of GC-rich DNA binding sites (b...
Gene Name
SCYL1
Uniprot ID
Q96KG9
Uniprot Name
N-terminal kinase-like protein
Molecular Weight
89630.605 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Unfolded protein binding
Specific Function
Cytosolic prostaglandin synthase that catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2) (PubMed:10922363). Molecular chaperone that localizes to genomi...
Gene Name
PTGES3
Uniprot ID
Q15185
Uniprot Name
Prostaglandin E synthase 3
Molecular Weight
18697.195 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Trna binding
Specific Function
Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. Active in progenitor and cancer cells. Inactive, or very low activity, in normal som...
Gene Name
TERT
Uniprot ID
O14746
Uniprot Name
Telomerase reverse transcriptase
Molecular Weight
126995.435 Da

Drug created on October 21, 2007 16:23 / Updated on June 04, 2019 06:14