PYR-41

Names

[ Name ]:
PYR-41

[Synonym ]:
Ethyl 4-{(4Z)-4-[(5-nitro-2-furyl)methylene]-3,5-dioxo-1-pyrazolidinyl}benzoate
4[4-(5-Nitro-furan-2-ylmethylene)-3,5-dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester
Benzoic acid, 4-[(4Z)-4-[(5-nitro-2-furanyl)methylene]-3,5-dioxo-1-pyrazolidinyl]-, ethyl ester
PYR-41

Biological Activity

[Description]:

PYR-41 is a specific and cell permeable inhibitor of ubiquitin-activating enzyme E1 with an IC50 of < 10 μM, with no or little activity at E2.

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> E1/E2/E3 Enzyme

Research Areas >> Cancer

[Target]

IC50: < 10 μM (E1)

[In Vitro]

PYR-41 increases total sumoylation in cells in addition to blocking ubiquitylation. PYR-41 attenuates cytokine-mediated nuclear factor-κB activation. PYR-41 also prevents the downstream ubiquitylation and proteasomal degradation of IκBα. Furthermore, PYR-41 inhibits degradation of p53 and activates the transcriptional activity of this tumor suppressor[1]. PYR-41 (50 μM) promotes accumulation of ubiquitinated proteins. PYR-41 causes a concentration-dependent (10-50 μM) decline in DUB activity in Z138 cells after 4 h. PYR-41 potently inhibits USP5 DUB activity, even at the lowest concentration (10 μM). PYR-41 potently (10-50 μM) inhibits the activity of various DUBs, determined to represent USP9x, USP5, USP14, UCH37 and UCH-L3. Co-treatment of Z138 cells with DTT and PYR-41 completely abolishes the accumulation of ubiquitinated proteins[2].

[Kinase Assay]

Rabbit or mouse E1 (apper 250 ng) is incubated with 32P-ubiquitin in 1× reaction buffer [50 mM Tris (pH 7.4), 0.2 mM ATP, 0.5 mM MgCl2] at room temperature for 15 min. In some experiments, the His-tagged mouse E1 is bound to TALON cobalt affinity resin before carrying out incubations and reactions. Mouse E1 and 32P-ubiquitin are added to the beads in 1× reaction buffer and incubated as for E1 reactions. Samples are heated in nonreducing SDS-PAGE sample buffer and resolved by SDS-PAGE. Thioesters with ubiquitin are visualized by Storm PhosphoImager.

[References]

[1]. Yang Y, et al. Inhibitors of ubiquitin-activating enzyme (E1), a new class of potential cancer therapeutics. Cancer Res. 2007 Oct 1;67(19):9472-81.

[2]. Kapuria V, et al. Protein cross-linking as a novel mechanism of action of a ubiquitin-activating enzyme inhibitor with anti-tumor activity. Biochem Pharmacol. 2011 Aug 15;82(4):341-9.

[Related Small Molecules]

Ginkgolic acid C15:1 | NSC232003 | CC122 | SZL P1-41 | TAK-243(MLN7243) | 2-Chloro-N-(3,4-dimethoxybenzyl)acetamide | PRT 4165 | SKPin C1 | TZ9 | CC 0651 | 2-D08 | PYZD 4409 | CC-885 | COH000

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Molecular Formula ]:
C₁₇H₁₃N₃O₇

[ Molecular Weight ]:
371.301

[ Exact Mass ]:
371.075348

[ PSA ]:
134.67000

[ LogP ]:
2.87

[ Appearance of Characters ]:
red to brown

[ Index of Refraction ]:
1.652

[ Storage condition ]:
?20°C

[ Water Solubility ]:
Soluble in DMSO at 5mg/ml with warming

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302-H317

[ Precautionary Statements ]:
P280

[ Hazard Codes ]:
Xn

[ Risk Phrases ]:
22-43

[ Safety Phrases ]:
36/37

[ RIDADR ]:
NONH for all modes of transport

Articles

TRPM8 channel as a novel molecular target in androgen-regulated prostate cancer cells.

Oncotarget 6 , 17221-36, (2015)

The cold and menthol receptor TRPM8 is highly expressed in prostate and prostate cancer (PC). Recently, we identified that TRPM8 is as an ionotropic testosterone receptor. The TRPM8 mRNA is expressed ...

Exosome-mediated extracellular release of polyadenylate-binding protein 1 in human metastatic duodenal cancer cells.

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Exosomes are small vesicles secreted from cells that transport their embedded molecules through bidirectional exocytosis- and endocytosis-like pathways. Expression patterns of exosomal molecules such ...

Aβ40 Reduces P-Glycoprotein at the Blood-Brain Barrier through the Ubiquitin-Proteasome Pathway.

J. Neurosci. 36 , 1930-41, (2016)

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