Highlights deCODE’s capabilities in structural biology and x-ray protein crystallography; may enable design of more effective anti-cancer compounds
Reykjavik, ICELAND, November 11, 2002 — deCODE genetics (Nasdaq/Nasdaq Europe:DCGN) today announced that scientists from the company’s biostructures group have successfully generated a three-dimensional image of how the cancer drug topotecan binds with the topoisomerase I enzyme and DNA to prevent cell division and proliferation. This is the first time that the mechanism of the drug has been elucidated in this way. The achievement demonstrates deCODE’s capabilities in protein crystallography and the company is applying this new information to discover new cancer therapies within the same family of compounds. The results of this work are published in the online edition of the Proceedings of the National Academy of Sciences, accessible on the internet at www.pnas.org.
deCODE’s work has made it possible to see exactly how topotecan binds to the topoisomerase-DNA complex, enabling a much more detailed understanding of how the camptothecin family of drugs disrupt the function of topoisomerase I. To do this, the deCODE team, based in Seattle, first developed a stable DNA-topisomerase complex that could be concentrated and crystallized. The team then conducted x-ray diffraction analysis of the crystal structure at Advanced X-Ray Analytical Services, deCODE’s subsidiary providing access to the Advanced Photon Source at Argonne National Laboratories.
“This is an example of our ability to solve even the most complex protein structures, either in support of our internal projects, as in this case, or for our biostructures clients,” said Lance Stewart, PhD, Vice President, deCODE BioStructures and a leader of the project.
Dr. Kari Stefansson, CEO of deCODE, added, “This work makes an important contribution to our understanding of a growing family of cancer treatments, and our drug discovery group is using this information to design new topoisomerase I inhibitors useful for fighting the disease. Our biostructures group is moreover demonstrating that it has valuable capabilities for designing more effective therapies for the gamut of human diseases.”
Topotecan is one of two FDA-approved synthetic analogues of camptothecin, a naturally-occuring alkaloid found in a Chinese shrub. Camptothecin’s potential as a tumor supressant was first recognized more than thirty years ago, and in the mid-1980s it was discovered that the compound was acting by binding to topoisomerase I, a crucial element in DNA replication. deCODE’s results announced today shed new light on how this binding occurs. Ordinarily, the topoisomerase interacts briefly with supercoiled DNA and makes a single nucleotide nick on one strand of the double helix. This enables the supercoil to relax, at which point the enzyme repairs the nick and detaches, leaving the DNA able to replicate. Topotecan stops this process by binding to the topoisomerase-DNA complex and stabilizing it, leaving the enzyme unable to repair the nick and detach. The ultimate result is cell death.
deCODE acknowledges the support for this work by the National Cancer Institute, the Pacific West Cancer Fund, the Argonne and Brookhaven National Laboratories, and the National Institute for General Medicine.
deCODE is using population genetics to create a new paradigm for healthcare. With its uniquely comprehensive population data, deCODE is turning research on the genetic causes of common diseases into a growing range of products and services — in gene and drug discovery, DNA-based diagnostics, pharmacogenomics, bioinformatics, and clinical trials. deCODE’s pharmaceuticals group, based in Chicago, and deCODE’s biostructures group, based in Seattle, conduct downstream development work on targets derived from deCODE’s proprietary research in human genetics as well as contract service work for pharmaceutical and biotechnology companies. deCODE is delivering on the promise of the new genetics.SM Visit us on the web at www.decode.com.
Any statements contained in this presentation that relate to future plans, events or performance are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are subject to a number of risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. These risks and uncertainties include, among others, those relating to technology and product development, integration of acquired businesses, market acceptance, government regulation and regulatory approval processes, intellectual property rights and litigation, dependence on collaborative relationships, ability to obtain financing, competitive products, industry trends and other risks identified in deCODE’s filings with the Securities and Exchange Commission. deCODE undertakes no obligation to update or alter these forward-looking statements as a result of new information, future events or otherwise.