PYR-41

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Chemical Structure| 418805-02-4 同义名 : -
CAS号 : 418805-02-4
货号 : A242472
分子式 : C17H13N3O7
纯度 : 99%+
分子量 : 371.3
MDL号 : MFCD01469983
存储条件：

Pure form Sealed in dry, store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 45 mg/mL(121.2 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
生物活性
靶点

  • E1 Activating

    Ubiquitin-activating Enzyme E1, IC50:<10 μM
描述 Ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2) and ubiquitin protein ligase (E3) are the key enzymes in protein ubiquitylation. PYR-41 is a pyrazone derivative that selectively inhibits E1 with an IC50 value less than 10 μM and a 95% inhibition was observed at the concentration of 50 μM. PYR-41 at 50 μM efficiently inhibited cyclin E degradation in vitro. PYR-41 reduced the level of E1∼Ub thioesters in retinal pigment epithelial cells with IC50 values ranging from 10-25 μM. The exposure of retinal pigment epithelial cells with PYR-41 (50 μM) for 30 min also blocked the accumulation of ubiquitin conjugates in response to the proteasome inhibitor ALLN. In U2OS cells, treatment of PYR-41 (50 μM) for 8 hours inhibited ubiquitylation and proteasomal degradation of a test substrate. In HeLa cells treated with EGF (100 ng/mL), pretreatment with PYR-41 for 15 min decreased the ligand-induced EGFR ubiquitylation. PYR-41 at 50 μM also reduced NF-κB activation in Hela cells by inhibiting the ubiquitylation of upstream signaling molecules and by blocking the proteasomal degradation of IκBα[3]. In a mouse model of cecal ligation and puncture (CLP)-induced sepsis, intravenous administration of PYR-41 (5 mg/kg) immediately after CLP significantly decreased serum levels of proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, and the levels of organ injury markers, such as AST, ALT, and LDH. PYR-41 treatment also reduced myeloperoxidase activity and suppressed apoptosis and caspase-3 degradation in the lungs of septic mice as compared to DMSO-treated group. PYR-41 also significantly promoted 10-day survival in mice with sepsis from 42% to 83%[4].
作用机制 PYR-41 selectively inhibits E1 possibly by covalently modifying the active site cysteine of E1.
细胞研究
细胞系 浓度 检测类型 检测时间 活性说明 数据源
HI5 insect cells Function assay 30 min Inhibition of N-terminal GST-tagged human UAE-catalyzed UAE-Ub thioester intermediate formation expressed in HI5 insect cells after 30 mins by immunoblotting analysis, IC50=10 μM 23360215
HI5 insect cells Function assay Inhibition of N-terminal GST-tagged human UAE-catalyzed [32P]-AMP:[a-32P]-ATP exchange expressed in HI5 insect cells by TLC analysis, IC50=6.4 μM 23360215
insect cells Function assay Inhibition of mouse recombinant His6-tagged UAE-catalyzed UAE-Ub thioester intermediate formation expressed in insect cells by SDS-PAGE analysis, IC50=10 μM 23360215
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.69mL

0.54mL

0.27mL

13.47mL

2.69mL

1.35mL

26.93mL

5.39mL

2.69mL
参考文献

[1]Yang Y, 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. doi: 10.1158/0008-5472.CAN-07-0568. PMID: 17909057.

[2]Matsuo S, Sharma A, Wang P, Yang WL. PYR-41, A Ubiquitin-Activating Enzyme E1 Inhibitor, Attenuates Lung Injury in Sepsis. Shock. 2018 Apr;49(4):442-450. doi: 10.1097/SHK.0000000000000931. PMID: 28661933; PMCID: PMC5745315.