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DUB Screening and Profiling Services

Deubiquitinating enzymes (DUBs) cleave ubiquitin off specific protein substrates and ubiquitin chains. Deubiquitination can have dramatic consequences for the protein of interest. Life Sensors is the principal biotechnology company to develop assays to characterize DUBs and their activity in vitro and in vivo. We offer our experts to fulfill your every DUB profiling need.

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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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