Belgium’s UCB and UK-based drug discovery company Domainex have jointly developed an experimental system to study the three-dimensional structure of Mitogen-activated protein kinase kinase (MAPKK), a protein which is over-active in many human cancers.
Domainex’s combinatorial domain hunting (CDH) technology is used to identify a form of the protein which can be produced in large quantities and which is suitable for structure-based drug discovery.
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CDH is a biotechnological method that involves the random fragmentation and screening of DNA fragments to identify those that produce large amounts of the protein of interest.
The technology enables the cloning and expression of soluble drug target protein domains in E. coli, followed by the identification of those constructs that are able to bind a ligand, facilitating the development of binding assays.
Researchers designed a class of molecules which inhibit MAPKK and have the potential to fight cancer, using the high-resolution structural information.
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UCB Discovery Research senior vice president Neil Weir said the class of MAPKK inhibitors which the UCB team discovered will benefit cancer patients.
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By GlobalDataDomainex research director Trevor Perrior said producing high-quality protein is crucial for successful drug research.
"We were extremely pleased that UCB could successfully utilise the constructs to generate high-resolution structural information and, most importantly, to use it to optimise their chemical series," Perrior added.
UCB is a biopharmaceutical company focused on the discovery and development of therapies to transform the lives of people with severe diseases of the immune system or of the central nervous system.
