PYR-41

PYR-41

Names
IUPAC name 4[4-(5-nitro-furan-2-ylmethylene)-3,5-dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester
Identifiers
CAS Number	418805-02-4
3D model (Jmol)	Interactive image
ECHA InfoCard	100.213.089
PubChem	5335621
SMILES CCOC(=O)C1=CC=C(C=C1)N2C(=O)/C(=C\C3=CC=C(O3)[N+](=O)[O-])/C(=O)N2
Properties
Chemical formula	C17H13N3O7
Molar mass	371.3 g/mol
Density	1.5±0.1 g/cm3
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

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

1. "biological activity of PYR41 in selleckchem". selleck chemicals LLC. Sep 25, 2014.
2. Kapuria V, Peterson LF, Showalter HD, et al. (Aug 15, 2011). "Protein cross-linking as a novel mechanism of action of a ubiquitin-activating enzyme inhibitor with anti-tumor activity.". Biochem Pharmacol. 82 (4): 341–349. doi:10.1016/j.bcp.2011.05.012. PMID 21621524.
3. Chen C, et al. (Jun 2014). "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. 142 (2): 307–319. doi:10.1111/imm.12255. PMID 24456201.