News Release

ChemGenex uses genomics approach to develop new anticancer drug, predict possible side effects

Peer-Reviewed Publication

Kureczka/Martin Associates

Gene expression changes in response to drugs in cell culture and living systems provide unique insights for their development and use

MENLO PARK, CA (October 30, 2001): Most genomics research is currently aimed at identifying and validating new gene targets for use in early stage drug discovery. However, genomics can also play a key role now in preclinical and clinical drug development, including predicting potential drug toxicities and helping developers design clinical trials, say scientists from ChemGenex Therapeutics. They discussed data today illustrating the use of chemical genomics approaches in evaluating the potential of their investigational drug called CeflatoninÔ against leukemias and human solid tumors. The researchers presented their findings at the American Association of Cancer Research – National Cancer Institute – European Organization for Research and Treatment of Cancer conference on “Molecular Targets and Cancer Therapeutics” taking place from October 29 to November 3 in Orlando, Florida.

“Understanding how genes perform in response to chemicals in cell cultures, as well as in diseased and normal tissues in living systems can help researchers identify and evaluate potential new drugs more efficiently than ever before,” said Dennis Brown, Ph.D., chairman, chief executive officer and founder of ChemGenex Therapeutics, Inc.

“Such knowledge can help spotlight possible drug toxicities, as well as identify which patients may best benefit from treatment with a specific drug,” he continued. “In addition, chemical genomics can aid in the design of efficient clinical trials by helping trial designers predict the most effective doses and dose scheduling, as well as provide key insights into drug bioavailability, distribution and metabolism. Using genomics in this way – to help patients receive most effectively those medicines that will be most useful to them – is a major goal of the genomics revolution.”

Based on its chemical genomics research, ChemGenex recently initiated Phase I/II human clinical trials with Ceflatonin as a potential treatment for patients with acute promyelocytic leukemia (APL). Ceflatonin is a natural product compound with demonstrated clinical activity as a single agent in hematological malignancies and research suggests other therapeutic uses for Ceflatonin in lymphoma and as a chemopotentiator in solid tumors. The research reported by ChemGenex today demonstrates that Ceflatonin affects specific genes and cellular pathways both in vitro and in vivo, including genes known to play a role in leukemia and key cellular transcription factors that are up-regulated in many solid tumors.

Ceflatonin Effect on Gene Expression Studied both In Vitro and In Vivo

In the research presented today, the ChemGenex scientists used a high-density array system to analyze the effects of Ceflatonin on gene expression within a human colon cancer cell line in vitro and on tumor growth and gene expression in fibrosarcoma cells grown in mice.

The researchers reported both up- and down-regulation of a number of genes in vitro, including effects on genes from the histone family and transcription factor Jun. Histone proteins are an integral part of the structure of chromosomes, and modified forms of these proteins are understood to play a role in leukemia. Jun is an important transcription factor that is regulated in response to a variety of growth factors, and up-regulation of this gene is associated with many solid tumors. Studies of gene expression in response to Ceflatonin in vivo demonstrated up-regulation of a variety of genes with transportation function as well as some unknown genes.

“Understanding the patterns of gene expression in response to Ceflatonin, both in vitro and in vivo, helps us to advance the development of this drug in multiple ways,” said Anil Sehgal, Ph.D. director of molecular biology and genomics at ChemGenex. “First, the patterns of gene expression seen in response to Ceflatonin help us pinpoint the precise mechanism of action for this drug. By studying alterations in the pattern of gene expression in relation to drug dose and schedule of administration, we can also predict potential toxicities and identify targets to improve Ceflatonin’s therapeutic index. In the future, patients may also be genetically screened to determine whether their disease gene profile matches the profile best suited for use with our drugs. This would be the realization of pharmacogenomics.”


About ChemGenex

ChemGenex Therapeutics, Inc. is a privately held pharmaceutical company whose strategy is to accelerate the development of novel small molecule therapeutics using chemical genomics, medicinal informatics, high-throughput drug screening systems and other leading-edge technologies for pharmaceutical R&D. These technologies allow the company to streamline the identification, evaluation and optimization of promising pharmaceutical leads and their subsequent preclinical and clinical development as drugs. ChemGenex is initially focusing its efforts in the fields of cancer and infectious disease, two areas characterized by unmet clinical needs and significant market opportunities. Since its establishment in 1999, ChemGenex has rapidly built a highly productive research effort and a formidable pipeline of compounds in stages of development ranging from lead optimization through Phase II clinical studies. The company has also established a joint venture with Elan Corporation focused on developing novel therapies for the treatment of cancer. ChemGenex is based in Menlo Park, California.

Harry Pedersen
Corporate Development
ChemGenex Therapeutics, Inc.
(650) 474-9800

For media:Joan Kureczka, (415) 821-2413 or Ellen
Martin, (510) 832-2044
Kureczka/Martin Associates

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