PYR-41
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Names | |
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IUPAC name
4[4-(5-nitro-furan-2-ylmethylene)-3,5-dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester
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Identifiers | |
3D model (JSmol)
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ChemSpider | |
ECHA InfoCard | 100.213.089 |
PubChem CID
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CompTox Dashboard (EPA)
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Properties | |
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).
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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
- ^ "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.