Targeting IRAK4 for Degradation with PROTACs
نویسندگان
چکیده
منابع مشابه
Development of Protacs to target cancer-promoting proteins for ubiquitination and degradation.
The proteome contains hundreds of proteins that in theory could be excellent therapeutic targets for the treatment of human diseases. However, many of these proteins are from functional classes that have never been validated as viable candidates for the development of small molecule inhibitors. Thus, to exploit fully the potential of the Human Genome Project to advance human medicine, there is ...
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The intracellular levels of many proteins are regulated by ubiquitin-dependent proteolysis. One of the best-characterized enzymes that catalyzes the attachment of ubiquitin to proteins is a ubiquitin ligase complex, Skp1-Cullin-F box complex containing Hrt1 (SCF). We sought to artificially target a protein to the SCF complex for ubiquitination and degradation. To this end, we tested methionine ...
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In the recently published Molecular Pathways article (1), Molineaux summarized the recent progress in the development of proteasome inhibitors for the treatment of cancer. The author stated that inhibition of NF-kB is one of the major mechanisms mediating the antitumor effect of proteasome inhibition. This notion has been supported by the finding that proteasome is responsible for the degradati...
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The design of proteolysis-targeting chimeras (PROTACs) is a powerful small-molecule approach for inducing protein degradation. PROTACs conjugate a target warhead to an E3 ubiquitin ligase ligand via a linker. Here we examined the impact of derivatizing two different BET bromodomain inhibitors, triazolodiazepine JQ1 and the more potent tetrahydroquinoline I-BET726, via distinct exit vectors, usi...
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ژورنال
عنوان ژورنال: ACS Medicinal Chemistry Letters
سال: 2019
ISSN: 1948-5875,1948-5875
DOI: 10.1021/acsmedchemlett.9b00219