UCB & Domainex collaboration provides valuable information on cancer drug target

• Combinatorial domain hunting technology aids identification of MEK protein suitable for structure-based drug discovery
• New structural information allowed UCB scientists to design a novel class of molecules which inhibit MEK

UCB and Domainex Ltd, a UK-based drug discovery company, have jointly published the results of a collaboration in the field of cancer drug discovery. Working together, the two companies have developed an experimental system to study the three-dimensional structure of Mitogen-activated protein kinase kinase (MAPKK, also known as MEK), a protein which is over-active in many human cancers. Using the high-resolution structural information, UCB scientists were able to design a novel class of molecules which inhibit MEK and which have the potential to combat cancer.

The key step in this work, reported in the latest edition of the Journal of Structural Biology, used Domainex’s Combinatorial Domain Hunting (CDH) technology to identify a form of the MEK protein which can be produced in large quantities and which is suitable for structure-based drug discovery. In the case of MEK, this was challenging because conventional methods proved unsuccessful, however Domainex’s CDH technology allowed the problem to be solved rapidly.

“The partnership with Domainex has been invaluable for our MEK discovery program. Successful collaborations, such as this, are a key part of UCB’s innovative and cutting-edge research. We hope that the novel class of MEK inhibitors which the UCB team discovered will bring benefits to patients,” said Neil Weir, Senior Vice President, Discovery Research UCB.

CDH is a biotechnological method that enables the identification of proteins for drug discovery and other applications. It involves the random fragmentation of DNA, and the screening of thousands of DNA fragments to identify those that produce large amounts of the protein of interest.

Trevor Perrior, Research Director at Domainex said: “Producing high-quality protein is crucial for successful drug research. Once again, Domainex’s CDH technology has proven to be invaluable, and the rapid identification of the best form of MEK from tens of thousands of other possibilities further validates our technology. We were extremely pleased that UCB could successfully utilize the constructs to generate high-resolution structural information and, most importantly, to use it to optimize their chemical series.”

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