MENLO PARK, CA (April 8, 2002): Chemical genomics – the study of the effect of chemicals on gene and protein expression in cells and living systems – offers key insights that can greatly facilitate drug development as well as aid the discovery and validation of new drug targets, say researchers from ChemGenex Therapeutics, Inc. Scientists from the privately held pharmaceutical company presented research this week at the American Association of Cancer Research (AACR) meeting in San Francisco, California demonstrating the use of such methods to advance the development of two of its investigational cancer drugs, now in clinical trials.
“The promise of genomics is, in many ways, already here and readily applicable to drug development,” said Dennis Brown, Ph.D., chairman and chief executive officer of ChemGenex. “Understanding how gene and protein expression are altered in cells and animal systems in response to a particular chemical can help validate drug discovery targets, as well as find potential compounds of interest. Such studies can also identify new activities and mechanisms of action for experimental drugs, provide insight into effective dosing regimens, and flag potential toxicities prior to clinical testing.”
Assessing Mechanisms of Action for Lead Drug and Analogs
In one poster presentation titled, “Identification of Molecular Targets for an Anti-Cancer Agent Quinamed(TM) Using High Density Expression Array Analysis," ChemGenex researchers demonstrated the use of high-density expression array (“DNA chip”) analysis to support the development of one investigational cancer drug, Quinamed(TM). Such studies have allowed the company to more clearly define the mechanism of action and to identify unique targets for the drug. The company is developing Quinamed(TM) as a potential treatment for solid tumors including glioblastoma, hormone refractory breast and prostate cancers.
Quinamed(TM) down-regulated genes including Jun B, protein kinase C, and EGF protein in human colon cancer cells and in tumors from animal models of colon cancer that treated with the drug. These genes are important to several major signal transduction pathways implicated in cancer. Interestingly, genes up-regulated by Quinamed(TM) included members of the tubulin protein family and other proteins involved in chromosomal organization, suggesting that the drug affects cell proliferation processes.
“The use of expression analysis greatly impacts our choices for follow-on biochemistry and cellular target studies with Quinamed(TM),” said Dr. Brown. “These tools allow us to efficiently discover potential molecular targets for our drug, as well as suggest specific medical indications for study. In addition, using this approach, we can also identify gene effects associated with potential side-effects or toxicity problems early in the drug development process.”
Anti-Angiogenic Properties Expand Second Drug’s Potential to Solid Tumors
Chemical genomics methods have predicted anti-angiogenic properties for ChemGenex’s second investigational drug, Ceflatonin(TM), a compound currently in Phase II clinical trials for hematologic malignancies. ChemGenex has now confirmed Ceflatonin(TM)’s ability to inhibit new blood vessel formation, as well as slow the growth of solid tumors, as shown by data presented in a second poster titled, “Solid Tumor Efficacy and a Unique Pattern of Angiogenic Inhibition by Ceflatonin(TM)”.
The ChemGenex scientists reported that in a standard mouse model of tumor growth, Ceflatonin(TM) inhibited the growth of solid tumors on a dose-dependent basis. Moreover, in a chick embryo assay of angiogenesis, Ceflatonin(TM) revealed a pattern of angiogenic inhibition that was unique compared to that produced by the chemotherapeutic drug Taxol(TM), which is known to be a potent angiogenesis inhibitor. Ceflatonin(TM) treatment resulted in a dramatic reduction in angiogenesis, with only a few fine vessels forming. In contrast, Taxol(TM) treatment resulted in more vessel formation, but with diffuse leakage of the red blood cells outside the vessels and the remnants of larger collapsed vessels.
“The novel changes seen in this model suggest that Ceflatonin(TM) inhibits new blood vessel formation through a novel mechanism of action that may make it valuable in treating solid malignancies,” said Dr. Brown. “As a result, we plan to expand our study of this compound beyond blood cell cancers to the potential treatment of solid tumors.”
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 field of cancer, an area 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.
Contacts:
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
Jkureczka@aol.com