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Celera Genomics Presents Further Data from Its Histone Deacetylase Inhibitor Program as Cancer Therapeutics.


SOUTH SAN FRANCISCO South San Francisco, city (1990 pop. 54,312), San Mateo co., W Calif.; inc. 1908. South San Francisco has several industrial parks; its manufactures include medical supplies and equipment, foods, paint, paper products, consumer goods, and clothing. , Calif. -- Celera Genomics Group (NYSE NYSE

See: New York Stock Exchange
:CRA See Community Reinvestment Act. ), an Applera Corporation business, today announced that its scientists will present three posters describing data from its histone deacetylase (HDAC HDAC Histone Deacetylase (biochemistry)
HDAC Heavy Duty Air Cylinder
) inhibitor program at the 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
) International Conference on Molecular Targets and Cancer Therapeutics meeting, being held November 14-18, 2005, in Philadelphia, PA.

Two of the posters that are being presented at the AACR meeting describe the inhibition of the HDAC enzyme activity Enzyme activity
A measure of the ability of an enzyme to catalyze a specific reaction.

Mentioned in: Glucose-6-Phosphate Dehydrogenase Deficiency
 that leads to tubulin tubulin /tu·bu·lin/ (too´bu-lin) the constituent protein of microtubules.

tu·bu·lin
n.
A globular protein that is the structural constituent of microtubules.
 and histone histone (hĭs`tōn), any of a class of protein molecules found in the chromosomes of eukaryotic cells. They complex with the DNA (see nucleic acid) and pack the DNA into tight masses of chromatin, which have the structure of coiled coils, much  acetylation acetylation /acet·y·la·tion/ (ah-set?i-la´shun) introduction of an acetyl radical into an organic molecule.

a·cet·y·la·tion
n.
. The first poster, entitled "CRA-024781: A Potent HDAC Inhibitor, with Antitumor an·ti·tu·mor   also an·ti·tu·mor·al
adj.
Counteracting or preventing the formation of malignant tumors; anticancer.

Adj. 1.
 Activity 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," reported extensive molecular profiling of CRA-024781, which is currently undergoing Phase I clinical assessment. CRA-024781 was found to inhibit human tumor cell growth at sub-micromolar concentrations in vitro, and exhibits effects on several mechanistic biomarkers in vitro. Additionally, CRA-024781 was shown to induce the upregulation of specific genes at early time points and down regulation of different genes at later time points in certain tumors which respond to CRA-024781. It may be possible to utilize such gene expression profiles to optimally target CRA-024781 to specific tumors. These preclinical findings further support the application of CRA-024781 as an anti-cancer therapy and may be incorporated into Celera's clinical trial strategy for CRA-024781.

The second poster, entitled "CRA-026440, a potent HDAC inhibitor, as an anti-cancer agent," focuses on Celera Genomics' HDAC backup compound CRA-026440 currently in preclinical development. CRA-026440 is a broad spectrum HDAC inhibitor that exhibited growth-inhibitory activities at sub-micromolar concentrations in vitro against a panel of human cancer cell lines. CRA-026440 has significant anti-tumor activity and was well tolerated in an HCT Hct
abbr.
hematocrit


HCT Hematocrit, see there
 116 tumor xenograft xenograft /xeno·graft/ (zen´o-graft) a graft of tissue transplanted between animals of different species; it may be concordant,  model. Additive efficacy was observed when CRA-026440 was combined with 5-FU or Avastin(R) in a colon tumor xenograft study. Furthermore, expression profiling analysis of CRA-026440 in vivo identified a set of genes that may contribute to the understanding and application of CRA-026440 as an HDAC inhibitor in anti-cancer therapy.

The third poster, entitled "The Design of Substituted Phenyl phenyl (fĕn`əl), C6H5, organic free radical or alkyl group derived from benzene by removing one hydrogen atom.  Hydroxamic Acids as Inhibitors of Histone Deacetylases," outlined the design of substituted phenyl hydroxamic acids as HDAC inhibitors. The elucidation of the three-dimensional structure of the HDAC-8 isoform with inhibitors bound at the active site was instrumental in the discovery and design of selective and potent HDAC inhibitors with good pharmaceutical properties. These studies provided additional data following the first report of the crystal structure of the enzyme HDAC-8 published by Celera Genomics in the journal Structure in July 2004.

"We're encouraged with the progress we've continued to make in our HDAC inhibitor program this year," said Robert Booth, Ph.D., Chief Scientific Officer of Celera Genomics. "These findings provide insights into the mechanism of action for these HDAC inhibitors and have generated a wealth of proprietary knowledge towards advancing our program in the most cost effective and timely manner."

About CRA-024781

HDAC inhibitors target HDAC enzymes resulting in inhibition of the proliferation of cancer cells and induction of cancer cell death or apoptosis(1). Celera Genomics reported in July 2005, the initiation of Phase I clinical testing for its novel HDAC inhibitor, CRA-024781, in patients with refractory solid malignancies. This Phase I trial is a dose-escalation study being conducted at the University of Chicago Hospitals The University of Chicago Hospitals form a major center for medical care and research in the Hyde Park neighborhood of Chicago, Illinois. They are affiliated with and run by the University of Chicago, and serve as teaching hospitals for students of the institution's Pritzker  in the Section for Hematology/Oncology. The objectives of the study are to determine the maximum tolerated dose and to evaluate the safety and pharmacokinetics of CRA-024781. Up to 40 patients are being enrolled in this study.

Histone deacetylation is carried out by a family of related HDAC enzymes. Inhibition of these enzymes causes changes to chromatin chromatin: see chromosome.  structure and to gene expression patterns, which result in the inhibition of proliferation of cancer cells and induction of apoptosis. Celera Genomics published the first three-dimensional structure of an HDAC enzyme in July 2004, and this information has been used to aid the design of a series of novel HDAC inhibitors.

(1)Johnstone, RW. Histone-Deacetylase Inhibitors: Novel drugs for the treatment of cancer. Nature Reviews Drug Discovery, 2002, 1:287-299.

About Celera Genomics and Applera Corporation

Applera Corporation consists of two operating groups. The Celera Genomics Group is engaged principally in the discovery and development of targeted therapeutics for cancer, autoimmune and inflammatory diseases. Celera Genomics is leveraging its proteomic, bioinformatic, and genomic capabilities to identify and validate drug targets, and to discover and develop small molecule therapeutics. It is also seeking to advance therapeutic antibody and selected small molecule drug programs in collaboration with global technology and market leaders. The Applied Biosystems Group serves the life science industry and research community by developing and marketing instrument-based systems, consumables, software, and services. Customers use these tools to analyze nucleic acids (DNA DNA: see nucleic acid.
DNA
 or deoxyribonucleic acid

One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes.
 and RNA RNA: see nucleic acid.
RNA
 in full ribonucleic acid

One of the two main types of nucleic acid (the other being DNA), which functions in cellular protein synthesis in all living cells and replaces DNA as the carrier of genetic
), small molecules, and proteins to make scientific discoveries and develop new pharmaceuticals. Applied Biosystems' products also serve the needs of some markets outside of life science research, which we refer to as "applied markets," such as the fields of: human identity testing (forensic and paternity testing); biosecurity, which refers to products needed in response to the threat of biological terrorism and other malicious, accidental, and natural biological dangers; and quality and safety testing, for example in food and the environment. Applied Biosystems is headquartered in Foster City, CA, and reported sales of nearly $1.8 billion during fiscal 2005. Celera Diagnostics, a 50/50 joint venture between Applied Biosystems and Celera Genomics, is focused on discovery, development, and commercialization of diagnostic products. Information about Applera Corporation, including reports and other information filed by the company with the Securities and Exchange Commission, is available at http://www.applera.com, or by telephoning 800.762.6923. Information about Celera Genomics is available at www.celera.com.

Forward-Looking Statements

Certain statements in this press release are forward-looking. These may be identified by the use of forward-looking words or phrases such as "believe," "expect," "intend," "should," and "planned," among others. These forward-looking statements are based on Applera Corporation's current expectations. The Private Securities Litigation Reform Act The Private Securities Litigation Reform Act of 1995 (PSLRA) implemented several significant substantive changes affecting certain cases brought under the federal securities laws, including changes related to pleading, discovery, liability, class representation and awards fees and  of 1995 provides a "safe harbor" for such forward-looking statements. In order to comply with the terms of the safe harbor, Applera Corporation notes that a variety of factors could cause actual results and experience to differ materially from the anticipated results or other expectations expressed in such forward-looking statements. These factors include but are not limited to: (1) Celera Genomics' unproven ability to discover, develop, or commercialize proprietary therapeutic products; (2) the risk that clinical trials of products that Celera Genomics do discover and develop will not proceed as anticipated or may not be successful, or that such products will not receive required regulatory clearances or approvals; (3) the uncertainty that Celera Genomics' products will be accepted and adopted by the market, including the risk that these products will not be competitive with products offered by other companies, or that users will not be entitled to receive adequate reimbursement for these products from third party payors such as private insurance companies and government insurance plans; (4) uncertainty of the availability to Celera Genomics of intellectual property protection, limitations on their ability to protect trade secrets, and the risk to them of infringement claims; and (5) other factors that might be described from time to time in Applera Corporation's filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Applera does not undertake any duty to update this information, including any forward-looking statements, unless required by law.

Copyright (C) 2005. Applera Corporation. All Rights Reserved. Applied Biosystems, Celera, Celera Diagnostics, Celera Discovery System, and Celera Genomics are trademarks of Applera Corporation or its subsidiaries in the U.S. and/or certain other countries.
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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