Domainex\'s CDH technology applied to cancer target, MEK kinase

1. This press release is for medical and trade journalists only
UCB and 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
Slough/ Cambridge, UK, 12th March 2012: 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.”
Further Information
Scott Fleming, Head of UK Communications
T +447702777378, E scott.fleming@ucb.com
Joanne McCudden, Head of Business Development
T +44 07775 437107, E Joanne.mccudden@domainex.co.uk
About UCB
UCB, Brussels, Belgium (www.ucb.com) is a global biopharmaceutical company focused on the
discovery and development of innovative medicines and solutions to transform the lives of people living
with severe diseases of the immune system or of the central nervous system. With more than 8,000
people in about 40 countries, the company generated revenue of EUR 3.2 billion in 2011. UCB is listed
on Euronext Brussels (symbol: UCB).
Feb 2012: UK/12MIS0021 1/2

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About Domainex
Domainex uses unique and proprietary technologies to resolve common bottlenecks facing the
pharmaceutical and biotechnology industries in the post-genomic era. Major discovery 'gaps' exist
between the vast amount of genomic information that is now available, the accessibility of the
corresponding proteins for use in target validation and drug discovery, and the identification of robust
hits in a cost effective manner. Founded in 2001, Domainex is a privately owned company based in
Cambridge, UK.
Domainex has developed a discovery platform, which enables rapid progression of drug discovery
projects from novel target through to Candidate Drug by means of its Combinatorial Domain Hunting
technology, LeadBuilder virtual hit screening software, and its integrated approach to medicinal and
computational chemistry.
Domainex’s patented CDH 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. This
enables binding assays to be developed, facilitating hit identification studies. In only 3-4 months, all
expressible ligand binding domains of a target protein are identified (from libraries of 20,000-100,000
constructs), enabling key rate limiting steps in early drug discovery to be easily overcome and resulting
in large time savings over standard approaches.
Domainex has also developed LeadBuilder - a virtual screening approach for targets which is specifically
aimed at quickly identifying hit molecules that are ideally suited for further development.
The experienced medicinal chemistry team has a proven track record in supporting biotech or university
groups by providing expertise to take hit compounds through lead optimization and on to candidate
selection. Three compounds to date arising from these collaborations are currently in clinical
evaluation, with two additional drugs in preclinical studies.
References
1. Meier C, Brookings DC, Ceska TA, Doyle C, Gong H, McMillan D, Saville GP et al. Engineering human
MEK for structural studies: A case study of combinatorial domain hunting. Journal of Structural
Biology (2012); 177:329-34.
Feb 2012: UK/12MIS0021 2/2