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Ubiquigent Ltd.

Dundee, GB

Ubiquigent is a unique enabler of ubiquitin-system targeted drug discovery

We provide access to the necessary expertise, Drug Discovery Services, high quality Research Tools and Chemistry required to support our commercial and academic partners in pursuing ubiquitin system-focused drug discovery programmes, and in undertaking basic research.

Drug Discovery Services - Regardless of whether you’re interested in screening for a novel ubiquitin deconjugating 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.

Chemistry - We have developed the first commercially available compound library designed to target deubiquitylase (DUB) enzymes, DUBtarget™-001 and assembled a collection of reference compounds reported as having activity and one or more DUB enzymes. ... Show more »

Ubiquigent is a unique enabler of ubiquitin-system targeted drug discovery

We provide access to the necessary expertise, Drug Discovery Services, high quality Research Tools and Chemistry required to support our commercial and academic partners in pursuing ubiquitin system-focused drug discovery programmes, and in undertaking basic research.

Drug Discovery Services - Regardless of whether you’re interested in screening for a novel ubiquitin deconjugating 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.

Chemistry - We have developed the first commercially available compound library designed to target deubiquitylase (DUB) enzymes, DUBtarget™-001 and assembled a collection of reference compounds reported as having activity and one or more DUB enzymes. We are now offering parties access to the library, associated data and further characterisation of the compound set using DUBprofiler™ to support their ubiquitin-system drug discovery programmes.

Research Tools - We offer one of the most extensive collections of high quality Research Tools available for the support of ubiquitin-system research. Each of these tools has been characterised in-house using, where possible, application relevant methods, to ensure their integrity and suitability for a specific purpose. Our Research Tools are available as single units or bulk quantities.

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Compound Libraries
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Deubiquitinating (DUB) 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... Show more »

Deubiquitinating (DUB) 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.

To address the under-utilisation of the ubiquitin system by medicinal chemistry we have taken two approaches:

Firstly we have 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.

The second is the development of 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 initially screened against a key DUB enzyme using Ubiquigent’s DUBprofiler™ platform. These data, as well as the physical library, are now available to access along with the capability to screen the library against any of the other 38 DUB enzymes available as part of DUBprofiler™ to provide starting points for drug development programmes.

If you are interested in learning more about our chemistry approach and ways to access our libraries please contact us directly at chemistry@ubiquigent.com

DUBtarget™-001

The first compound library comprising novel small molecules designed to target deubiquitylase enzymes

Ubiquigent Ltd and The Drug Discovery Unit at the University of Dundee have jointly developed the first commercially available compound library designed to target deubiquitylase (DUB) enzymes, DUBtarget™-001.

The library has been screened against USP2 (a key target opportunity in cancer) employing our DUBprofiler™ – DUB affinity and selectivity profiling – platform. These data, as well as the physical library, are now available to access along with the option to screen the library against any of the other 37 DUB enzymes available as part of DUBprofiler to help inform starting points for drug development programmes.

We are now offering parties access to the library, associated data and further characterisation of the compound set using DUBprofiler to support their ubiquitin-system drug discovery programmes.

Commercial Offering

Ubiquigent is now seeking partners interested in gaining access to DUBtarget-001.

The library is available to be accessed in a number of ways, including:
•In its physical form for those wishing to screen it using their in-house assay platforms
•In a virtual form along with the screening data generated against USP2
•In a virtual form along with screening data generated against any other DUB enzyme(s) from the DUBprofiler panel. In this case the data will be generated upon request

If you’re interested in exploring how you can access the DUBtarget-001 DUB targeted library please contact us directly at chemistry@ubiquigent.com

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Deubiquitinating enzymes
Compound Profiling
Price on request

DUBprofiler™

The easiest way to quickly identify novel DUB inhibitors

Screen your compounds across any or all of the 38 individual DUB targets on our panel of enzymes representative of the entire human DUB superfamily.

DUBprofiler is one of our standard services designed to help you quickly identify DUB... Show more »

DUBprofiler™

The easiest way to quickly identify novel DUB inhibitors

Screen your compounds across any or all of the 38 individual DUB targets on our panel of enzymes representative of the entire human DUB superfamily.

DUBprofiler is one of our standard services designed to help you quickly identify DUB (deubiquitylase) inhibitors. Our service is available in a range of different formats:
•DUBprofiler SPT for single-point analysis
•DUBprofiler IC50 for IC50 determinations
•DUBprofiler HT for screening larger numbers of compounds ◦As part of this service we can offer high precision and accuracy with ultra-low volume compound dispensing (down to 2.5nl) to enable addition of the assay reagents directly to the compound in 100% DMSO. This is particularly suited to screens where compound solubility and availability is a concern.

The key features of our DUBprofiler service.

DUBprofiler is:
•Comprehensive – ability to screen across any or all of the 38 individual DUB targets on our panel representative of the entire DUB family
•Robust – ubiquitin-rhodamine(110)-glycine substrate based-assay with multiple controls
•Flexible – screen at single concentrations (SPT) or determine IC50 values using standard 8-point half-log concentration-effect curves (IC50)
•Scalable – screen any combination of compound(s) vs. DUB
•Efficient – simple service procedure using electronic submission forms (supplied on request)
•Fast – rapid screening cycles

The process
•Contact us and let us know what type of screen you require (SPT, IC50 or HT)
•We’ll send you an electronic submission form that lets you select the compound-DUB combination you require. We’ll also send you a set of barcoded tubes for submission of your compounds
•Our submission forms also allow you to generate as many quotations as you like based on different combinations of compound numbers and DUBs
•Once you’ve finalised your study design, email us the submission form and send us your compounds
•Once we’ve received the compounds we’ll immediately schedule them for screening and keep you updated on project progress
•Once complete we’ll send you a fully annotated data report and arrange a post project meeting to answer any questions you might have

To learn more about our DUBprofiler screening services and to discuss your specific requirements, email us at services@ubiquigent.com

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Custom Cell-Based Assays
Price on request

As pathways and functions are unravelled, new and attractive ubiquitin/UBL cascade drug discovery targets are coming to light with relevance across many key therapeutic areas.

We have now successfully developed and delivered a number of HTS-compatible assays and kits enabling leading pharmaceutical companies to conduct... Show more »

As pathways and functions are unravelled, new and attractive ubiquitin/UBL cascade drug discovery targets are coming to light with relevance across many key therapeutic areas.

We have now successfully developed and delivered a number of HTS-compatible assays and kits enabling leading pharmaceutical companies to conduct screening campaigns against ubiquitin cascade targets (DUBs, E3s and others) of high therapeutic value.

Projects completed include the design and development of E3 ligases HTS assays and the delivery of a reagent kit to conduct a screening campaign versus 1m+ compounds. Various hit deconvolution assays have also been delivered to dissect the mechanism of action of the hits identified from these screens.
The combination of our extensive experience in working with these pathways and our access to one of the widest collections of Research Tools allows Ubiquigent’s Custom Assay Development team to support pharmaceutical and biotechnology companies in translating discoveries into lead programmes.

Many of our assays have been developed from first principles starting with little or no data from the literature to guide the construction of the assay. Ubiquigent can research, design, manage and deliver the entire programme to help you to achieve success in your ubiquitin system HTS campaigns.

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Deubiquitinase (DUB) Assays
Price on request

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™ 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.

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Ubiquitin Ligase Assays
Price on request

IDOL-E3 Ligase Assay

The E3 ubiquitin ligase Inducible Degrader of LDLR (IDOL) has recently been identified as a target of significant interest in Alzheimer’s Disease6 (AD). IDOL has a demonstrated a cellular role in the regulation and turnover of the LDL receptor (LDLR) in lipid homeostasis and to date has offered a route to... Show more »

IDOL-E3 Ligase Assay

The E3 ubiquitin ligase Inducible Degrader of LDLR (IDOL) has recently been identified as a target of significant interest in Alzheimer’s Disease6 (AD). IDOL has a demonstrated a cellular role in the regulation and turnover of the LDL receptor (LDLR) in lipid homeostasis and to date has offered a route to the modulation of hypercholesterolaemia and cardiovascular disease1-5. Now, targeting IDOL provides a novel and exciting route to the modulation of apolipoprotein E- (ApoE) and β-amyloid- (Aβ) clearance in the brain offering potential therapeutic value in the treatment of AD6.

We have successfully developed one of the first commercially available assays to allow researchers to screen against IDOL in either HTS or non-HTS formats.

Our IDOL assay is now available to support research programmes with the objectives of identifying modulators of this putative drug target. As with our other services, the assay can be configured in HTS or non-HTS formats depending on your requirements. If you would like to explore access to our IDOL-E3 ligase assay please contact as at services@ubiquigent.com

Why IDOL?

  • Loss of IDOL expression in transgenic mice increases brain LDLR, decreases ApoE, soluble and insoluble Aβ, reduces amyloid plaque burden and ameliorated neuroinflammation6
  • Targeting (down-regulating) IDOL-catalysed ubiquitylation of LDLR increases cell surface [LDLR] and LDL uptake, highlighting the potential value of this target in addressing Alzheimer’s Disease6 and cardiovascular disease4
  • The LDLR is essential for the uptake of LDL cholesterol and the regulation of plasma lipoprotein levels1
  • An inherited loss-of-function mutation in the LDLR gene in humans or poor diet can elevate plasma LDL levels, reduce LDL clearance and accelerate atherosclerosis and the risk of cardiovascular disease2,3
  • The E3 ligase IDOL is up-regulated by the sterol-activated transcription factors LXR alpha and LXR beta which increase IDOL expression resulting in ubiquitylation and subsequent degradation of the LDLR4,5

References

  1. Russell, D.W., W.J. Schneider, T. Yamamoto, K.L. Luskey, M.S. Brown, and J.L. Goldstein. 1984. Domain map of the LDL receptor: sequence homology with the epidermal growth factor precursor. Cell. 37:577-585.
    Brown, M.S., and J.L. Goldstein. 1986. A receptor-mediated pathway for cholesterol homeostasis. Science. 232:34-47.
  2. Tolleshaug, H., K.K. Hobgood, M.S. Brown, and J.L. Goldstein. 1983. The LDL receptor locus in familial hypercholesterolemia: multiple mutations disrupt transport and processing of a membrane receptor. Cell. 32:941-951.
  3. Zelcer, N., C. Hong, R. Boyadjian, and P. Tontonoz. 2009. LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor. Science. 325:100-104.
  4. Zhang, L., L. Fairall, B.T. Goult, A.C. Calkin, C. Hong, C.J. Millard, P. Tontonoz, and J.W. Schwabe. 2011. The IDOL-UBE2D complex mediates sterol-dependent degradation of the LDL receptor. Genes Dev. 25:1262-1274.
  5. Choi J, Gao J, Kim J, Hong C, Kim J, Tontonoz P. 2015. The E3 ubiquitin ligase Idol controls brain LDL receptor expression, ApoE clearance, and Aβ amyloidosis. Sci Transl Med. 7(314):314
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Cell-Based Assays
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Enzyme Assays
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Biochemical Assays
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Biology
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Lead Identification and Validation
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Drug Discovery & Development
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Specialized Cell-Based Assays
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Biochemistry & Molecular Biology
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Drug Discovery
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Hydrolase Assays
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Ligase Assays
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2017-06-12 13:02:56 -0400

Net Promoter Score of 10 received for Compound Profiling.

Additional Ratings: satisfaction with deliverable: 10, satisfaction with timeliness: 10.
2017-05-30 14:14:15 -0400

Net Promoter Score of 10 received for Compound Profiling.

Additional Ratings: satisfaction with deliverable: 10, satisfaction with timeliness: 10.

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