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MethylGene Displays HDAC Posters at AACR Annual Meeting.


MONTREAL -- Company discloses proprietary HDAC HDAC Histone Deacetylase (biochemistry)
HDAC Heavy Duty Air Cylinder
 clinical assay method and HDAC oncology research findings

MethylGene Inc. (TSX TSX Toronto Stock Exchange (TSE before April, 2002)
TSX Transfer from Stack Pointer to Index
TSX True Space Extension
: MYG) disclosed a novel research method and research findings, including preclinical data for MGCD MGCD Maximum Gapless Coverage Distance 0103, for its histone deacetylase (HDAC) program in oncology. The information was disclosed in two poster sessions which were displayed at the 96th American Association for Cancer Research Wikipedia is not the place for advertisement or self-advertising.

The American Association for Cancer Research (AACR) is an organization based in Philadelphia, Pennsylvania, that focuses on all aspects of cancer research including basic, clinical and translational
 (AACR AACR American Association for Cancer Research
AACR Anglo-American Cataloging Rules
AACR Australasian Association of Cancer Registries
AACR African Armed Conflicts Resolved
) Annual Meeting in Anaheim, California from April 16-20, 2005.

In a poster entitled "Development of Whole Cell HDAC Enzyme Assay to Analyze Inhibitory Activity of MGCD0103 In Vitro in vitro /in vi·tro/ (in ve´tro) [L.] within a glass; observable in a test tube; in an artificial environment.

in vi·tro
adj.
In an artificial environment outside a living organism.
 and In Vivo," (poster #606) the Company described its proprietary Whole Cell HDAC Enzyme Assay that monitors the inhibitory activity of MGCD0103 both in vitro and in vivo. MGCD0103 is currently in Phase I trials in solid tumours and hematological malignancies and this proprietary assay method is being used to monitor the pharmacodynamics pharmacodynamics /phar·ma·co·dy·nam·ics/ (-di-nam´iks) the study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of their actions and effects with their chemical  of the drug in Phase I patients.

Using this novel assay method, the Company also provided data that demonstrated the inhibitory activity of MGCD0103 on histone deacetylase. The inhibitory activities of MGCD0103, MS-275 (Berlex Labs) and SAHA (Merck) were compared in various cultured human cancer cells. MGCD0103 appeared to be the most potent inhibitor across the various cancer cell lines. In addition, the drug can inhibit, in a dose-dependent manner, whole cell HDAC activity in human peripheral white blood cells White blood cells
A group of several cell types that occur in the bloodstream and are essential for a properly functioning immune system.

Mentioned in: Abscess Incision & Drainage, Bone Marrow Transplantation, Complement Deficiencies
 ex vivo and in white blood cells isolated from mice treated in vivo.

In a second poster entitled "Specific Inhibition of HDAC8 by Antisense antisense, DNA or RNA manipulated in a laboratory so that its components (nucleotides) form a complementary copy of normal, or "sense," messenger RNA (mRNA; see nucleic acid).  Leads to Growth Arrest and Apoptosis of Human Cancer Cells," (poster #1807), MethylGene presented target-validation data showing that specific inhibition of HDAC8 induces growth arrest and apoptosis in human cancer cells but not in normal cells, in a dose-dependent and time-dependent manner. It was noted that HDAC8 is distinct from other class I enzymes in sequence homology and that HDAC8 expression is elevated in various human cancer cell lines both at the mRNA and protein levels. The research implicates HDAC8 in pathways that are essential for cancer growth and apoptosis and could be important in the creation of next generation inhibitors.

"These observations and target validation data are important for guiding and developing novel isotypic selective small molecule inhibitors for cancer and other disease indications in MethylGene's research and development portfolio," stated Dr. Jeffrey M. Besterman, Sr. Vice President of Research and Development.

About HDAC

Histone deacetylases (HDAC) are a family of 11 enzymes that are involved in the regulation of gene expression Gene modulation redirects here. For information on therapeutic regulation of gene expression, see therapeutic gene modulation.
For vocabulary, see Glossary of gene expression terms


.
 and as such may be master regulators for disease. It has been established in the scientific literature and observed by MethylGene's scientists and collaborators that isotypic selective inhibition of certain HDAC enzymes may have the potential to impact diseases including cancer, diabetes, inflammation, cardiovascular and neurodegenerative diseases. MethylGene is currently developing MGCD0103, an isotypic selective inhibitor targeting specific HDAC enzymes involved in the regulation of tumour suppressor genes in cancer. MGCD0103 is currently in Phase I dose-escalating monotherapy trials for solid tumours and hematological malignancies.

About MethylGene

MethylGene is a publicly traded biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutics in cancer and infectious disease. Two cancer product candidates, MG98, partnered with MGI MGI Mouse Genome Informatics
MGI Modular Gateway Interface
MGI McKinsey Global Institute
MGI Military Geographic Information
MGI Marine Geological Institute
MGI Policy on the Management of Government Information (Canada) 
 Pharma for North America and MGCD0103, partnered with Taiho Pharmaceutical for certain Asian countries, are currently in clinical trials.

MG98 has entered a randomized ran·dom·ize  
tr.v. ran·dom·ized, ran·dom·iz·ing, ran·dom·iz·es
To make random in arrangement, especially in order to control the variables in an experiment.
 two-step Phase II combination trial with interferon alpha in metastatic Metastatic
The term used to describe a secondary cancer, or one that has spread from one area of the body to another.

Mentioned in: Coagulation Disorders


metastatic

pertaining to or of the nature of a metastasis.
 renal cell cancer. MGCD0103 is currently in Phase I dose-escalation monotherapy trials against solid tumours and hematological malignancies. In collaboration with Merck, MethylGene is developing small molecule beta-lactamase inhibitors to overcome antibiotic resistance. MethylGene has a portfolio of preclinical programs for its kinase and histone deacetylase (HDAC) inhibitors for both oncology and non-oncology indications, and is exploiting its core HDAC expertise for the treatment of neurodegenerative diseases with EnVivo Pharmaceuticals. Please visit MethylGene's website at www.methylgene.com.

Except for historical information, this press release may contain forward-looking statements, which reflect the Company's current expectation regarding future events. These forward-looking statements involve risk and uncertainties,(which can be found in the Company's prospectus dated June 18, 2004 and can be found on www.sedar.com) which may cause but are not limited to, changing market conditions, the successful and timely completion of clinical studies, the establishment of corporate alliances, the impact of competitive products and pricing, new product development, uncertainties related to the regulatory approval process and other risks detailed from time to time in the Company's ongoing quarterly and annual reporting.
COPYRIGHT 2005 Business Wire
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2005, Gale Group. All rights reserved. Gale Group is a Thomson Corporation Company.

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Publication:Business Wire
Geographic Code:1CANA
Date:Apr 14, 2005
Words:739
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