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Ubiquitin & PROTAC

Home Biology & Pharmacology In Vitro Biology Ubiquitin & PROTAC

Ubiquitin & PROTAC

While intracellular signal cascade transduction is usually regulated by protein phosphorylation, gene expression is influenced by epigenetics. The proteins that regulate these signals are subject to the “production-degradation” balance in the cells to maintain the homeostasis of cells. The ubiquitin-proteasome system is responsible for the regulation of protein degradation process in the cell. The imbalance of protein degradation directly affects the physiological state of the cell, which is the direct cause of many rare diseases such as Angelman’s Syndrome (also known as Happy Puppet Syndrome).

Further investigation also found that the imbalance of protein degradation is related to many diseases like cancer and neurodegenerative diseases. The study of the protein ubiquitin-proteasome system has further improved the understanding of the protein degradation in the cell, opening up a new field of drug discovery.

Furthermore, the novel therapeutic strategy expanded the drug discovery perspective from the regulation of target protein activity (Inhibition/activation) to the regulation of target protein existence, in other words, from inhibiting to destroying.

ChemPartner’s in vitro biology team has developed a series of assays for protein ubiquitin-proteasome system, including deubiquitination enzyme activity, E1 activating enzyme activity, E2 conjugating enzyme activity, and the E3 ligase activity assays, which can be used to identify inhibitors or activators in the system.

Assay Platform for Ubiquitin System

Meanwhile, the research on the ubiquitin-protease system also gave birth to a newdrug discovery approach – PROTAC (Proteolysis Targeting Chimera) – which utilizes the unbiquitin-proteasome system to directly degrade the protein of interest (POI). PROTACs recruit the POI to the E3 ligase then trigger the proteasome-mediated degradation. Due to the “event-driven” nature of PROTACs, it is different from traditional drugs which inhibit the functional activity of the target protein through long-term and high affinity binding, thus it became an emerging technique for “undruggable targets” drug discovery. ChemPartner has developed a series of corresponding assays which can detect the degree of ubiquitination on the POI at the biochemical level to evaluate the PROTAC activity.

PROTAC Assay Platform

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