4-[4-[(5-硝基-2-呋喃基)亚甲基]-3,5-二氧代-1-吡唑烷基]苯甲酸乙酯

PYR-41 is the first cell permeable inhibitor of ubiquitin-activating enzyme E1,irreversibly inhibits ubiquitin-activating enzyme activity.It is a pyrazone compound that showed little or no activity on E2,E3. Unexpectedly, despite of ubiquitylation inhibition, PYR-41 also enhances total sumoylation in cells. PYR41 also blocks the downstream ubiquitination and ubiquitination-dependent protein degradation or other ubiquitination-mediated cellular activities. Besides, PYR-41 inhibits degradation of p53, a tumour suppressor and also activates the transcription activity of it. PYR-41 and related pyrazones selectively kill transformed p53 expressing cells, suggesting that E1 inhibitors may be potential therapeutics in cancer.