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DUB Screening and Profiling Services

As a LifeSensors customer you will be consulting with a member of our team to discuss the scope of work relating to your project. We have many years of experience in ubiquitin research and are here to help you answer your research questions. We work with clients to better understand their compounds as an important step in the drug discovery process. 

The DUB screening process is a customized job.. LifeSensors will work with individual customers to put together a timeline for their individual project process. LifeSensors will identify the best screening platform for your project, predict and overcome potential pitfalls, and provide you with rapid results.   Our team’s combined experience in the ubiquitin field will enable us to understand your project at a deep level, accelerate your data collection, and aid you in interpreting the results.  We will accelerate and enhance your drug discovery efforts, allowing you identify the most promising hit compounds and advance them based on potency and selectivity to cellular and in vivo studies.

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Technology Overview

DUB Ubiquitin Linkage Specificity

Our scientists can resolve the specificity of your DUB’s cleavage. This includes determining if your DUB can cleave certain chain types and substrates.

Linkage-selective polyubiquitin cleavage: This figure demonstrates the ability of USP30 to selectively cleave lysine 6-linked tetraubiquitin chains. For each chain linkage type, USP30 was incubated with each indicated tetraubiquitin for 4 hours, and the reaction was analyzed at successive time points, displayed as successive gel lanes from left to right. While some DUB activity is observable across most chain types, the complete consumption of lysine-6 linked tetraubiquitin by USP30 far outpaces the all other chain types.between chain cleavage by USP30. Source

DUB Screening & Compound Profiling

LifeSensors is ready and able to test compound potency and selectivity in a variety of DUB assays. We have a variety of fluorogenic DUB substrates, ranging from industry standards like Ub-Rhodamine 110 to our patented arsenal of physiological DUB substrates and reporters. We can identify and optimize the best assay for your DUB of interest. Using either our in-house library or your own compounds, we can perform screening and dose-response studies. Once you have identified inhibitors or activators of your DUB, we can then screen your compounds for selectivity against our in-house panel of 25 DUB enzymes from several prominent enzyme families. We also perform biophysical studies to assess target engagement, such as fluorescence thermal shift assays. Following the in vitro work, we can help you monitor downstream biomarkers for your compound's in vivo activity. Why LifeSensors? Because we are the only company with the expertise to see the details that matter in DUB drug development. Contact us today.

Inhibition Frequency Distribution: Typical frequency distribution of compound inhibition levels from a screening campaign and subsequent primary confirmation. As expected, the library screen produces a normal distribution of inhibition percentages, while compounds selected for follow-up exhibit significant, reproducible inhibition of DUB activity.

DUB selectivity profiling: Selectivity profile a potent USP7 inhibitor measured by Ub-Rhodamine assay. As demonstrated by the IC50 curves, the compound is at least one order of magnitude more potent against USP7 and USP47 than any of the other 8 DUBs in this panel, including 4 USP family DUBs. 

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