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).
Forward looking statements: UCB
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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.
Deborah Cockerill
Sciad Ltd
deborah@sciad.com
07930 317729
www.sciad.com
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Posted: March 2012
