Linking Ubiquitin Research to Drug Discovery

Novel DUB-targeted compound libraries to support ubiquitin system focused drug discovery.

We have developed one of the first libraries of DUB-targeted small molecules, DUBtarget™-001, developed in collaboration with the Drug Discovery Unit and the University of Dundee.

The library has been developed to provide access to novel starting points for drug discovery programmes.  The library can be accessed in its physical form (solid and/or DMSO stock solutions) for screening in your in-house assays.  Alternatively, we have already screened the library against the full DUB enzyme panel available in our DUBprofiler platform to identify hit compounds. These data are now available for immediate access.

Further DUB-targeted libraries will be made available on a non-exclusive basis however if you have key DUBs of interests we would be pleased to discuss the development of more targeted libraries that could be made available exclusively to you.

We have also assembled a Reference Compound Library. These are compounds that have been reported in the literature as having activity at a range of different deubiquitinating enzymes (DUB).  As such they represent potential tools that can be used to further investigate the function of the ubiquitin system and may in themselves also represent valid starting points for drug development programmes.  If required we can source this collection for screening using DUBprofiler.

If you are interested in learning more about our chemistry approach and ways to access our libraries please Contact us directly.

 

Targeted chemical libraries: the keys to unlock the ubiquitin system

Although the widespread use of target-focused libraries has led to the rapid expansion of novel chemistry as a research tool in drug discovery to exploit many classes of drug target, the ubiquitin system still remains a largely untapped medicinal chemistry opportunity. Protein kinases, on the other hand, have become one of the most important classes of drug targets for the pharmaceutical industry over the last decade, following on from the exploitation of kinase-focused libraries for at least the last two decades. Like protein phosphorylation by kinases, protein ubiquitylation regulates many aspects of cell function and provides a wealth of drug target opportunities across many therapeutic areas including cancer, cardiovascular, metabolism, inflammation, neurodegeneration and infectious diseases.

Following the massive breakthroughs in cancer therapy that have come about from our understanding of how to intervene in kinase signalling systems, it is becoming increasingly clear that other major cell signalling processes, such as those dependent on ubiquitin ligation and de-ubiquitination, possess the potential for further breakthroughs of perhaps similar therapeutic magnitude. The development of kinase drugs has been possible largely because of the intimate interplay of biology and focused medicinal chemistry using libraries of probe compounds designed specifically for the purpose. Along with the major advances in high-quality biological assays being driven by Ubiquigent and others, the stage is now set for a similar impact of focused medicinal chemistry – it seems that the time has now come to realise this potential.”  Dr John Harris CChem FRSC, founder of BioFocus.