PYR-41
目录号 : GC15771
An irreversible inhibitor of ubiquitin-activating enzyme
Cas No.:418805-02-4
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| 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. | |
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.
| Cas No. | 418805-02-4 | SDF | |
| 化学名 | 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 | ||
| 分子式 | C17H13N3O7 | 分子量 | 371.3 |
| 溶解度 | ≥ 18.55mg/mL in DMSO | 储存条件 | Store at -20° C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。