UCB and Domainex Collaboration Provides Valuable Information on Cancer Drug Target
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|Monday, 12 March 2012 07:00 (UTC + 1)|
Slough/ Cambridge, UK, 12th March 2012 / B3C newswire / - 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.”
Forward looking statements: UCB
There is no guarantee that new product candidates in the pipeline will progress to product approval or that new indications for existing products will be developed and approved. Products or potential products which are the subject of partnerships, joint ventures or licensing collaborations may be subject to differences between the partners. Also, UCB or others could discover safety, side effects or manufacturing problems with its products after they are marketed.
Moreover, sales may be impacted by international and domestic trends toward managed care and health care cost containment and the reimbursement policies imposed by third-party payers as well as legislation affecting biopharmaceutical pricing and reimbursement.
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.
Joanne McCudden, Head of Business Development