PYR41

PYR41 is an irreversible inhibitor of ubiquitin-activating enzyme (E1) with an IC₅₀ value of less than 10 µM.¹ PYR41 specifically inhibits ubiquitin-thioester bond formation (IC₅₀ = 6.4 µM) and not adenylation.² It is selective for E1 over ubiquitin-conjugating enzyme (E2) but does inhibit autoubiquitination of the HECT domain ubiquitin protein ligase (E3) Nedd4 at a concentration of 50 µM in an autoubiquitination assay.¹ It inhibits proteasome-dependent and -independent ubiquitination and protein degradation when used at a concentration of 50 µM. PYR41 prevents activation of NF-κB, ubiquitination of TNF receptor-associated factor 6 (TRAF6), and proteasomal degradation of IκBα. It prevents degradation and induces transcriptional activity of the tumor suppressor p53 and preferentially induces apoptosis of E1A-transformed RPE cells expressing wild-type p53 over non-transformed RPE cells when used at concentrations ranging from 1 to 20 µM. PYR41 also increases net cellular sumoylation and irreversibly cross-links proteins such as JAK2 and Bcr-Abl.^1,3

WARNING This product is not for human or veterinary use.

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