Elucidating Crystal Structure of Challenging Protein - MEK

March, 2012

Domainex worked closely with UCB Pharma to develop 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 gained, 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 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.

Meier C, et al. (Feb 2012) Engineering human MEK-1 for structural studies: A case study of combinatorial domain hunting. J Struct Biol. 2012 Feb;177(2):329-34