PYR 41 Chemical Properties

Melting point:

228 - 235°C

Density 

1.486±0.06 g/cm3(Predicted)

storage temp. 

-20°C

solubility 

Soluble in DMSO at 5mg/ml with warming

form 

powder

pka

7.43±0.20(Predicted)

color 

red to brown

Sensitive 

Light Sensitive

Stability:

Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 week.

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)

InChIKey

ARGIPZKQJGFSGQ-LCYFTJDESA-N

SMILES

C(OCC)(=O)C1=CC=C(N2C(=O)C(=CC3=CC=C([N+]([O-])=O)O3)C(=O)N2)C=C1

Safety Information

Hazard Codes 

Xn

Risk Statements 

22-43

Safety Statements 

36/37

WGK Germany 

3

PYR 41 Usage And Synthesis

Description

Pyr41 (418805-02-4) inhibits ubiquitin activating enzyme E1 (>60% inhibition at 10 μM) with little or no activity against E2 or E3. Cell permeable

Uses

PYR 41 is an irreversible and cell-permeable UBE1 inhibitor.

Definition

ChEBI: PYR-41 is an ethyl ester resulting from the formal condensation of the carboxy group of 4-{4-[(5-nitrofuran-2-yl)methylidene]-3,5-dioxopyrazolidin-1-yl}benzoic acid with ethanol. It is an irreversible and cell-permeable inhibitor of ubiquitin-activating enzyme E1. It has a role as an EC 6.2.1.45 (E1 ubiquitin-activating enzyme) inhibitor and an antineoplastic agent. It is an ethyl ester, a member of furans, a C-nitro compound, a member of pyrazolidines and a benzoate ester.

Biochem/physiol Actions

PYR-41 is a cell permeable inhibitor of Ubiquitin activating enzyme (E1) with little or no activity against E3, E2, or caspase enzymatic activity.

in vitro

in addition to blocking ubiquitylation, pyr-41 was found to increase total sumoylation in cells. pyr-41 could attenuate cytokine-mediated nuclear factor-kbactivation. this correlated with inhibition of nonproteasomal ubiquitylation of traf6, which is important to ikbkinase activation. pyr-41 also prevented the downstream ubiquitylation and proteasomal degradation of ikba. moreover, pyr-41 has demonstrated effective uae e1 inhibition as well as some off-target inhibition of the other ubiquitin regulatory enzymes and signal-transducing proteins, suggesting it is a nonspecific inhibitor [1].

storage

Store at -20°C

References

[1] YILI YANG. Inhibitors of ubiquitin-activating enzyme (E1), a new class of potential cancer therapeutics.[J]. Cancer research, 2007, 67 19: 9472-9481. DOI:10.1158/0008-5472.can-07-0568
[2] LIXIN MI. Cancer preventive isothiocyanates induce selective degradation of cellular alpha- and beta-tubulins by proteasomes.[J]. The Journal of Biological Chemistry, 2009, 284 25: 17039-17051. DOI:10.1074/jbc.m901789200
[3] TOMOHIKO MAEHAMA. Nucleolar stress induces ubiquitination-independent proteasomal degradation of PICT1 protein.[J]. The Journal of Biological Chemistry, 2014, 289 30: 20802-20812. DOI:10.1074/jbc.m114.571893

PYR 41(418805-02-4)Related Product Information

• LFM-A13
• Brefeldin A
• Geldanamycin
• TYRPHOSTIN AG 879
• Bortezomib
• PR-619
• Degrasyn (WP1130)
• NSC697923
• MG-132
• Nutlin-3