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Methyltransferase Inhibitors

Methyltransferases are involved in epigenetic gene regulation by covalent modification of histones. An ever-increasing body of evidence indicates that these enzymes are significant in many diseases, and that they play important roles in stem-cell biology. In particular, a number of these enzymes are known to be of relevance in some mechanisms of carcinogenesis.

Domainex has solved the key technical drug discovery challenges associated with KMTs, including the discovery of hit series. We can now approach any member of the KMT target class with confidence and would welcome discussion on potential collaboration.  Contact us for more information.

Domainex's KMT Discovery Programme

Domainex has cloned and expressed a number of lysine methyltransferase enzymes (KMTs) using either conventional cloning techniques or its proprietary Combinatorial Domain Hunting (CDH) technology.

So far, two proteins have been crystallised and their structures determined by x-ray diffraction analysis. These protein structures are proving extremely useful for the design of inhibitors.

A variety of biochemical assay systems have been established by identifying the best choice from a range of substrates.  For example: peptide, full-length histone H3, or higher complexes of H3. These reagents and assay systems will allow Domainex to screen against a wide range of KMTs.

Finally, Domainex has identified lead-like KMT inhibitors to its lead epigenetic target, G9a, using its LeadBuilder virtual hit screeningapproach.  At present one of these programmes is in the hit-to-lead stage of drug discovery and continues to progress well. In parallel, Domainex is building a focussed library screening set that will be useful in the development of inhibitors to additional future KMT targets.

 

Click here to access Domainex's Presentation from 3rd Epigenetics Summit in Boston 2012.