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 (JSmol)	Interactive image;
ChemSpider	4492747;
ECHA InfoCard	100.213.089
PubChem CID	5335621;
CompTox Dashboard (EPA)	DTXSID30416554 ;
	InChI 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- Key: ARGIPZKQJGFSGQ-LCYFTJDESA-N;
	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

^ "biological activity of PYR41 in selleckchem". selleck chemicals LLC. Sep 25, 2014.
^ 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.
^ 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. PMC 4008238. PMID 24456201.

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[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. PMC 4008238. PMID 24456201.

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