Pyr41

SKU: orb1300603

Description

PYR-41 is a cell-permeable small molecule that selectively inhibits the ubiquitin-activating enzyme E1 without affecting E2 enzymes. It is widely used in vitro and in vivo to study ubiquitination pathways in cancer research, neurodegenerative disease models, and cellular protein degradation mechanisms.

Research Area

Protein Biochemistry

Key Properties

• CAS Number: 418805-02-4
• MW: 371.3
• Purity: >98%
• Formula: C₁₇H₁₃N₃O₇
• SMILES: CCOC(=O)c1ccc(cc1)N1NC(=O)\C(=C\c2ccc(o2)[N+]([O-])=O)C1=O
• Target: UAE (ubiquitin activating enzyme)
• Solubility: Soluble in DMSO (up to 25 mg/ml).

Bioactivity

• Target IC50:
  E1:< 10 μM
• In Vitro:
  PYR-41 (50 μM) inhibits activity of ubiquitin-activating enzyme E1 by over 90%. PYR-41 could be a target for nucleophilic attack and potentially reacts with the active site cysteine of E1. PYR-41 efficiently blocks cyclin E degradation. PYR-41 decreases the level of E1fUb thioesters in cells with a IC50 of between 10 and 25 μM, and prevents proteasome inhibitor–induced accumulation of ubiquitylated proteins. PYR-41 increases total sumoylation in cells and in cell harboring temperature-sensitive E1. PYR-41 is able to inhibit both proteasome-dependent and proteasome-independent activities of ubiquitylation. PYR-41 (50 μM) attenuates 1 ng/mL IL-1α-mediated nuclear factor-κB activation by >60% through preventing the downstream ubiquitylation and proteasomal degradation of IκBα. PYR-41 inhibits degradation of p53 and activates the transcriptional activity of p53, which enable its differentially killing transformed p53-expressing cells. PYR-41 blocks ubiquitination reactions but paradoxically leads to the accumulation of high MW ubiquitinated proteins. PYR-41 also has equal or greater inhibitory activity against several deubiquitinases (DUBs) in intact cells and purified USP5 in vitro. PYR-41 also mediates cross-linking of specific protein kinases (Bcr-Abl, Jak2) to inhibit their signaling activity.

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Apoptosis, E1 activating enzyme, E1 Enzyme, E1/E2/E3 Enzyme, E2 conjugating enzyme, E2 Enzyme, E1Enzyme, E3Enzyme, E3 ligating enzyme, E2Enzyme, E3 Enzyme, Inhibitor, inhibit, PYR41, PYR-41, PYR 41, Ubiquitin activating enzyme, Ubiquitin conjugating enzyme, Ubiquitin ligase, Ubiquitin-activating Enzyme E1

Compound Identifiers

PubChem CID

5335621