PYR-41

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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.[1]
Unexpectedly, despite of ubiquitylation inhibition, PYR-41 also enhances total sumoylation in cells.[2]
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.[3] PYR-41 and related pyrazones selectively kill transformed p53 expressing cells, suggesting that E1 inhibitors may be potential therapeutics in cancer.

References[edit]

  1. ↑ biological activity of PYR41 in selleckchem(link). selleck chemicals LLC.Sep 25, 2014.
  2. ↑ "Protein cross-linking as a novel mechanism of action of a ubiquitin-activating enzyme inhibitor with anti-tumor activity.".Biochem Pharmacol.Aug 15, 2011;82(4)
    341–349.doi:10.1016/j.bcp.2011.05.012.
  3. ↑ "Ubiquitin-activating enzyme E1 inhibitor PYR-41 attenuates angiotensin II-induced activation of dendritic cells via the IκBa/NF-κB and MKP1/ERK/STAT1 pathways.".Immunology.Jun 2014;142(2)
    307–319.doi:10.1111/imm.12255.PMC:4008238.


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