PYR41

PYR41 is an irreversible inhibitor of ubiquitin-activating enzyme (E1) with an IC50 value of less than 10 µM. PYR41 specifically inhibits ubiquitin-thioester bond formation (IC50 = 6.4 µM) and not adenylation. 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. It inhibits proteasome-dependent and -independent ubiquitination and protein degradation when used at a concentration of 50 µM. PYR41 prevents activation of NF-kappaB, ubiquitination of TNF receptor-associated factor 6 (TRAF6), and proteasomal degradation of IkappaBalpha. 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.Formal Name: 4-[4-[(5-nitro-2-furanyl)methylene]-3,5-dioxo-1-pyrazolidinyl]-benzoic acid, ethyl ester. CAS Number: 418805-02-4. Molecular Formula: C17H13N3O7. Formula Weight: 371.3. Purity: >95%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 20 mg/mL, DMSO: 20 mg/mL, DMSO:PBS (pH 7.2) (1:1): 0.5 mg/ml. lambdamax: 284, 364 nm. SMILES: O=C(OCC)C1=CC=C(N2C(/C(C(N2)=O)=C\C3=CC=C([N+]([O-])=O)O3)=O)C=C1. InChi Code: InChI=1S/C17H13N3O7/c1-2-26-17(23)10-3-5-11(6-4-10)19-16(22)13(15(21)18-19)9-12-7-8-14(27-12)20(24)25/h3-9H,2H2,1H3,(H,18,21)/b13-9-. InChi Key: ARGIPZKQJGFSGQ-LCYFTJDESA-N.