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BIOPHARMACEUTICAL MODELS OFFER CHEAP, EFFECTIVE SCREENING & METABOLIC ASSESSMENT OF COMPOUNDS
A major problem facing R&D departments in pharmaceutical companies today is the high cost associated with drug development and testing. The overall process of taking a new drug candidate from initial concept to approved product in the clinic can be as high as £275m or more. Optimisation of therapeutic properties for maximal efficacy must be achieved without introducing changes in the design of the compound that would have toxic potential. Often, millions can be spent before discovering that biochemical activity in the body is responsible for producing undesirable side effects or toxic reactions. Cytochrome P450s, a family of enzymes (many of which exist in the liver), modify foreign molecules found in the blood. In some cases, these modifications can have toxic results or may make the drug ineffective against the target disease. The Lewis P450 Models allow drug companies, at the earliest stages of product development, to assess potential drug interactions using a panel of P450 computer models to determine which drug candidates should be ruled out of a drug development program, or for promising candidates, what further research and development is required. These models, already licensed to a number of pharmaceutical companies, are proving highly effective as one of many tools used in early drug development. In addition to allowing timely screening of potential reactions between drug candidates and certain liver enzymes, the Lewis P450 Models have also proved predictive on several occasions, a significant advance in 3D molecular modeling. In addition, the models have been used successfully to design an improved derivative of 2,5 bis(trifluoromethyl)-7-benzyloxy-4-trifluoromethyl coumarin based on predictions of its likely interaction with CYP3A4. “This P450 model screening system extends the range of early-stage design, screening and profiling tools needed by drug companies in order to prioritise and direct their efforts in developing effective, life-saving pharmaceuticals,” said Professor David Lewis, Professor of Structural Biology, University of Surrey (UK). Dr. Mike Murray, Associate Vice President of BTG’s BioPharmaceuticals Business Unit, added “BTG looks forward to working with Professor Lewis and new licensees on this powerful tool by providing commercial access to the models and any improvements which may arise.”
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