BioWorld International Correspondent
LONDON Astex Technology Ltd. signed a collaboration with Aventis Pharmaceuticals AG to elucidate how P450 enzymes involved in drug metabolism complex with Aventis’ compounds.
This is Astex’s second deal with big pharma to use its proprietary X-ray crystallography techniques to assess how P450 enzymes interact with drug compounds. At the same time the company, based in Cambridge, said it has received the first milestone from its other P450 partner, AstraZeneca AB. The payment relates to Astex solving the first 3-dimensional crystal structure of a P450 enzyme at the end of 2001.
No financial details of the deal with Aventis were disclosed.
Timothy Haines, Astex’s CEO, said the progress the company has made in solving P450 crystal structures endorses its abilities in structure-based drug discovery. “Determination of the structures of additional human P450s is under way, and will continue to provide invaluable information for the rational design of drugs with reduced metabolic and toxicity problems.”
P450s, the most significant group of drug-metabolizing enzymes in humans, are the cause of adverse reactions to many marketed drugs, and many compounds fail in development because of the way they interact with P450. Certain drugs also may be ineffective or even harmful as a result of patient-specific variations in P450s.
These proteins are among the most difficult types of structures to solve, as they are large and complex, and partly embedded within lipid membranes. Once released from the membranes, they are unstable.
Astex has developed proprietary high-throughput X-ray crystallography technologies. They industrialize the process for producing proteins and crystallizing them, going from crystals to structure automatically, rather than depending on experts to interpret the crystal structure.
As it solves each P450 structure, its pharmaceutical partners will be able to assess how the compounds complex with these enzymes, and modify them accordingly. Astex expects to sign multiple deals on assessing how P450 structures bind to any given compound.
Astex was founded in 1999, and to date has raised £29 million (US$41.7 million) in venture capital.