PYR-41 |
| رقم الكتالوجGC15771 |
PYR-41 هو مثبط انتقائي ومنفذ للخلية من إنزيم E1 المنشط للأوبيكويتين مع IC 50 <10 ميكرومتر ، مع نشاط ضئيل في E2 و E3
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 418805-02-4
Sample solution is provided at 25 µL, 10mM.
Ubiquitylation is catalyzed by the sequential action of ubiquitinactivating enzyme (E1), a ubiquitin-conjugating enzyme (E2) and a ubiquitin protein ligase (E3). Ubiquitylation is essential to numerous cellular and developmental processes, including protein quality control, growth, apoptosis, antigen presentation, DNA repair, and signal transduction. PYR-41, 4[4-(5-nitro-furan-2-ylmethylene)-3,5-dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester, is a selective inhibitor of Ubiquitin-Activating Enzyme (E1).
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].
In vivo: No animal in vivo data have been published so far.
Clinical trial: Up to now, PYR-41 is still in the preclinical development stage.
Reference:
[1] Yang Y1 Kitagaki J, Dai RM, Tsai YC, Lorick KL, Ludwig RL, Pierre SA, Jensen JP, Davydov IV, Oberoi P, Li CC, Kenten JH, Beutler JA, Vousden KH, Weissman AM. Inhibitors of ubiquitin-activating enzyme (E1), a new class of potential cancer therapeutics. Cancer Res. 2007 Oct 1;67(19):9472-81.
| Cell experiment [1, 2]: | |
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Cell lines |
RPE cells, U2OS cells transfected with GFPu; RAW 264.7 cells |
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Preparation method |
The solubility of this compound in DMSO is >18.6mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
RPE cells: 50 μmol/L; 30 min; 37°CRAW 264.7 cells: 5, 10, and 20 μM |
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Applications |
In RPE cells, PYR-41 markedly reduced Ub~E1 thioesters with IC50 between 10 and 25 μmol/L. PYR-41 also blocked accumulation of ubiquitin conjugates in response to the proteasome inhibitor ALLN. In U2OS cells transfected with GFPu, PYR-41 inhibited both ubiquitylation and proteasomal degradation of GFPu. In RAW 264.7 cells stimulated by LPS, PYR-41 (10 and 20 μM) restored the expression levels of IκB to 89% and 95% of those in the non LPS-stimulated RAW 264.7 cells, respectively. PYR-41 also reduced TNF-α levels. |
| Animal experiment [2]: | |
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Animal models |
Male C57BL/6 mice with sepsis induced by cecal ligation and puncture (CLP) |
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Dosage form |
5 mg/kg; intravenous injection immediately after CLP |
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Application |
In septic mice induced by CLP, PYR-41 significantly reduced serum levels of proinflammatory cytokines TNF-α, IL-1β, and IL-6 by 79%, 77%, and 89%, respectively. PYR-41 also reduced serum levels of organ injury markers AST, ALT, and LDH by 27%, 43%, and 52%, respectively. Treatment with PYR-41 improved the morphologic appearance of lung tissues and showed a 74% reduction in histology injury score. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Yang Y1 Kitagaki J, Dai RM, Tsai YC, Lorick KL, Ludwig RL, Pierre SA, Jensen JP, Davydov IV, Oberoi P, Li CC, Kenten JH, Beutler JA, Vousden KH, Weissman AM. Inhibitors of ubiquitin-activating enzyme (E1), a new class of potential cancer therapeutics. Cancer Res. 2007 Oct 1;67(19):9472-81. [2]. Matsuo S1, Sharma A, Wang P, et al. PYR-41, A Ubiquitin-Activating Enzyme E1 Inhibitor, Attenuates Lung Injury in Sepsis. Shock. 2017 Jun 28. | |
| Cas No. | 418805-02-4 | SDF | |
| Chemical Name | ethyl 4-[(4Z)-4-[(5-nitrofuran-2-yl)methylidene]-3,5-dioxopyrazolidin-1-yl]benzoate | ||
| Canonical SMILES | CCOC(=O)C1=CC=C(C=C1)N2C(=O)C(=CC3=CC=C(O3)[N+](=O)[O-])C(=O)N2 | ||
| Formula | C17H13N3O7 | M.Wt | 371.3 |
| الذوبان | ≥ 18.55mg/mL in DMSO | Storage | Store at -20° C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6932 mL | 13.4662 mL | 26.9324 mL |
| 5 mM | 0.5386 mL | 2.6932 mL | 5.3865 mL |
| 10 mM | 0.2693 mL | 1.3466 mL | 2.6932 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 27 reference(s) in Google Scholar.)
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