Linking Ubiquitin Research to Drug Discovery

Ubiquigent is dedicated to providing a range of state-of-the-art Drug Discovery Services to support the rapidly growing academic and commercial drug discovery interests in this field.

Regardless of whether you’re interested in screening for a novel ubiquitin deubiquitylase enzyme (DUB) inhibitor, a modulator of a ubiquitin ligase (E3s) or wish to investigate any other part of the ubiquitin system, we have the assays and capabilities available to support your research programmes.

DUBprofiler is one of our standard services designed to help you quickly identify DUB inhibitors. DUBprofiler is available in two formats; you can choose to screen compounds at either single or multiple concentrations in either high-throughput (HT) or non-HT modes allowing studies to be run in the most efficient way regardless of compound numbers.

DUBprofiler has been employed by world leading groups for determination of the affinity and selectivity of DUB targeted compounds in support of their drug discovery programmes.

Alternatively, access our novel compound library of DUB inhibitors, DUBtarget-001.  We’ve screened our library through the entire DUBprofiler panel and identified novel hit compounds across the panel.  Those data are immediately available to support your DUB focused projects.

REDOXprofiler is also one of our standard services and comprises two complementary assay readouts for identifying REDOX Cycling Compounds (RCCs). RCCs may be identified as ‘hits’ in compound screens against enzymes such as cysteine proteases, including four of the six sub-families of DUBs, and are generally regarded in such screening campaigns as ‘false positives’. The mechanism of action of RCCs involves the generation of Reactive Oxygen Species (ROS) and the oxidation and thus inactivation by these of the target enzyme’s catalytic cysteine. Thus it is critical to determine whether compounds identified as hits in an assay screen (such as DUBprofiler™) have an RCC or a non-RCC mechanism of action prior to further investment in those compound series in hit-to-lead programmes. REDOXprofiler™ may be used to screen any scale of compounds and has utility for supporting drug discovery programmes targeting cysteine proteases such as cathepsins and caspases and protein tyrosine phosphatases as well as DUBs.

We offer cell based assays to support your target and biomarker discovery and validation projects including assays which may utilise Horizon knock out cell lines and associated CRISPR/Cas9 gene editing technologies.  We are also developing DUBprofiler-Cell™, an assay to determine the in-cell DUB target engagement profile of molecules arising from your drug discovery programmes.  As part of this latter service we will also be able to report to you the DUBome profile (expressed and detectable DUBs) of a cell line of choice.  This DUBome may be determined and compared between cell lines which may be treated or untreated with cell signalling activating ligands and/or other stimuli and/or may carry a genetically defined mutation (see Horizon technology above) in support of target identification and validation objectives.

Our IDOL assay is an example of a standard assay that offers the ability to screen compounds for activity at a specific E3 ligase. IDOL has recently been identified as a target of significant interest in Alzheimer’s disease and in the regulation and turnover of the LDL receptor (LDLR) in lipid homeostasis.  Our IDOL assay is also available in multiple formats depending on your requirements.

Other assays may also be developed utilising technology platforms such as those available through our collaboration with CAST:

  • Cell imaging
  • Flow cytometry
  • Mass  spectrometry

Specialised services such as high sensitivity surface plasmon resonance for characterising protein-protein and protein-small molecule interactions are also accessible by Ubiquigent.

Our Custom Drug Discovery Services capability is where we develop new assays on a case-by-case basis in response to our client’s requests. Once developed we can run these assays on your behalf, transfer them to your lab or use a combination of the two approaches.

For further details on any of our services, follow the links on the left or Contact us directly to discuss your requirements.