Astex granted patent covering use of crystal structure of human cytochrome P450 3A4, the most important drug metabolising enzyme in man
Cambridge, UK, January 24 2005.
Astex Technology, the fragment-based drug discovery and development company, today announced issuance of patent GB2395718 covering the use of the crystal structure of human cytochrome P450 3A4, the most important drug metabolising enzyme in man. It is estimated that as many as 50% of all known drugs interact with this form of cytochrome P450 and as such it represents a major problem for drug developers.
Astex has been actively involved in human cytochrome P450 research since the company’s formation and Astex scientists were the first group to successfully solve the crystal structures of human cytochromes P450, 3A4 and 2C9. This has resulted in an extensive patent portfolio covering methods for purifying cytochrome P450 protein, preparing cytochrome P450 crystals, obtaining the crystal structure coordinates and their use in drug discovery and development.
"Grant of this first patent on a human cytochrome P450 crystal structure is an important milestone for Astex," commented Timothy Haines, Chief Executive. "The insights provided by the crystal structures of cytochromes P450 should improve the success rates and economics of drug development and result in safer and more effective new medicines."
(1) GB2395718. Astex Technology Limited. Inventors: Jhoti, H; Kirton, SB; Tickle, I; Vonrhein, C; Williams,PA. Crystal structure of cytochrome P450 3A4 and its use.
Notes to Editors
Cytochromes P450 (CYP450) are the most significant group of drug-metabolising enzymes in humans and CYP450 3A4 is generally regarded as the most important member of this group. The action of these enzymes is the cause of adverse drug reactions to many marketed drugs and drug-combination therapies and many failures of novel drugs during their development have been attributed to their interactions with this class of enzymes. For example, drugs may be metabolized too rapidly by CYP450 before they have had time to be effective, or they may be broken down into smaller molecules which are toxic. Certain drugs may also inhibit the activity of a CYP450 enzyme which is involved in the metabolism of another drug that, given at the same time, can become elevated in the patient to levels which can cause side effects or become dangerous.
Although it is estimated that as many as 50% of all known drugs interact with CYP450 3A4, this particular isoform is also the most poorly understood member of the group with respect to its drug metabolising action and, as such, it represents a major problem in drug development.
The insight provided by knowledge of the crystal structures of cytochrome P450s and how drugs bind to these enzymes allows for the design of drug compounds with more optimal drug metabolism properties thereby reducing attrition rates in drug development and resulting in safer and more effective new medicines.
About Astex
Astex is a biotechnology company producing novel small molecule therapeutics. Using its pioneering fragment-based drug discovery approach, Astex has rapidly established a broad pipeline of next generation, molecularly targeted oncology drugs, the first of which will enter clinical trials in 2005.
Astex’s leading position in fragment-based drug discovery derives from its integrated discovery engine, Pyramid™. High-throughput X-ray crystallography and other biophysical techniques are used to identify drug fragments bound to target proteins and to help in directing the transformation of the fragments, using efficient medicinal chemistry, into potent, selective drugs. Pyramid™ has been successfully applied across a wide variety of therapeutic targets, including those regarded as ‘intractable’ by the pharmaceutical industry, resulting in potential new drug leads for the treatment of cancer, inflammation and Alzheimer’s disease.
Astex’s unprecedented productivity in lead discovery has been endorsed by drug discovery alliances with major pharmaceutical companies including AstraZeneca, Aventis, Boehringer Ingelheim, Fujisawa Pharmaceutical Company Ltd., Mitsubishi Pharma and Schering AG. Astex was established in 1999 and is well financed by leading, blue chip US and European investors (Abingworth, Advent International, Alta Partners, Apax, GIMV, HypoVereinsbank, Oxford Bioscience Partners, Schering AG and the University of Cambridge).