WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406481
Description: PYR-41 is a ubiquitin-activating enzyme inhibitor (UBE1 inhibitor). PYR-41 blocks ubiquitination reactions but paradoxically leads to the accumulation of high MW ubiquitinated proteins. PYR-41 also mediated cross-linking of specific protein kinases (Bcr-Abl, Jak2) to inhibit their signaling activity. PYR-41 has demonstrated anti-tumor activity in animal studies, partially selective protein cross-linking may represent an alternate approach to affect signal transduction modules and ubiquitin cycle-regulatory proteins for cancer therapy. (Biochem Pharmacol. 2011 Aug 15;82(4):341-9.) (Note: PYR-41 in solution may exist as a mixture of E- and Z- isomers. HPLC may show two peaks depending on conditions).
MedKoo Cat#: 406481
Chemical Formula: C17H13N3O7
Exact Mass: 371.07535
Molecular Weight: 371.3
Elemental Analysis: C, 54.99; H, 3.53; N, 11.32; O, 30.16
Synonym: PYR41; PYR 41; PYR-41.
IUPAC/Chemical Name: ethyl 4-(4-((5-nitrofuran-2-yl)methylene)-3,5-dioxopyrazolidin-1-yl)benzoate
InChi Key: ARGIPZKQJGFSGQ-LCYFTJDESA-N
InChi Code: 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)/b13-9-
SMILES Code: O=C(OCC)C1=CC=C(N2NC(/C(C2=O)=C/C3=CC=C([N+]([O-])=O)O3)=O)C=C1
Appearance: Brown solid powder
Purity: >98% (or refer to the Certificate of Analysis). Note: PYR-41 in solution may exist as a mixture of E- and Z- isomers. HPLC may show two peaks depending on conditions.
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
|Biological target:||PYR-41 is a selective and cell permeable inhibitor of ubiquitin-activating enzyme E1 with an IC50 of < 10 μM, with little activity at E2 and E3|
|In vitro activity:||In sepsis, release of proinflammatory cytokines from macrophages is the main cause of the “cytokine storm” (8). The effectiveness of PYR-41 in attenuating NF-κB activation in macrophages was first determined. The expression levels of IκB, an NF-κB inhibitor, in RAW 264.7 cells were decreased by 54% at 30 min after lipopolysaccharide (LPS) stimulation (Fig. 1A). With PYR-41 treatment at 10 and 20 μM, the expression levels of IκB were restored to 89% and 95% of those in the non LPS-stimulated RAW 264.7 cells, respectively (Fig. 1A). The TNF-α levels in cultured media grown with RAW 264.7 cells were then measured. After 4 h-LPS stimulation, the TNF-α levels increased from 0.03 to 1.34 ng/ml, while treatment with PYR-41 at doses of 5, 10, and 20 μM decreased TNF-α levels by 38%, 81%, and 94%, respectively (Fig. 1B). The viability of RAW 264.7 cells were also examined by MTS assay and observed no adverse effects of PYR-41 on cell viability (Fig. 1C). Shock. 2018 Apr; 49(4): 442–450. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745315/|
|In vivo activity:||PYR-41 was administered to mice that underwent sepsis-induction by CLP (cecal ligation and puncture). At 20 h after CLP, serum levels of proinflammatory cytokines TNF-α, IL-1β, and IL-6 were markedly increased compared to the sham (Fig. 2, A–C). In contrast, treatment with PYR-41 significantly reduced their levels by 79%, 77%, and 89%, respectively, compared to the vehicle (Fig. 2, A–C). Serum levels of organ injury markers AST, ALT, and LDH were also elevated after CLP, while their levels were reduced by 27%, 43%, and 52%, respectively, with PYR-41 treatment (Fig. 2, D–F). Additionalluy, after treatment with PYR-41, the morphologic appearance of lung tissues was improved (Fig. 3A). The severity of the lung damage was futher graded and showed a 74% reduction in histology injury score in the treatment group compared to the vehicle (Fig. 3B). Excessive immune cell infiltration, especially by neutrophils, is one important factor causing lung injury in sepsis (18). Lung myeloperoxidase (MPO) activity, a marker of neutrophil infiltration (19), was markedly increased after CLP by 19-fold compared to the sham, while it was significantly reduced by 64% with PYR-41 treatment compared to the vehicle (Fig. 3C). Shock. 2018 Apr; 49(4): 442–450. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745315/|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
The following data is based on the product molecular weight 371.3 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
|Formulation protocol:||1. 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. 2. You X, Xu DD, Zhang D, Chen J, Gao FG. PYR-41 and Thalidomide Impair Dendritic Cell Cross-Presentation by Inhibiting Myddosome Formation and Attenuating the Endosomal Recruitments of p97 and Sec61 via NF-κB Inactivation. J Immunol Res. 2018 Jul 5;2018:5070573. doi: 10.1155/2018/5070573. PMID: 30069488; PMCID: PMC6057288. 3. Shu Q, Lai S, Wang XM, Zhang YL, Yang XL, Bi HL, Li HH. Administration of ubiquitin-activating enzyme UBA1 inhibitor PYR-41 attenuates angiotensin II-induced cardiac remodeling in mice. Biochem Biophys Res Commun. 2018 Oct 20;505(1):317-324. doi: 10.1016/j.bbrc.2018.09.100. Epub 2018 Sep 22. PMID: 30249396.|
|In vitro protocol:||1. 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. 2. You X, Xu DD, Zhang D, Chen J, Gao FG. PYR-41 and Thalidomide Impair Dendritic Cell Cross-Presentation by Inhibiting Myddosome Formation and Attenuating the Endosomal Recruitments of p97 and Sec61 via NF-κB Inactivation. J Immunol Res. 2018 Jul 5;2018:5070573. doi: 10.1155/2018/5070573. PMID: 30069488; PMCID: PMC6057288.|
|In vivo protocol:||1. Shu Q, Lai S, Wang XM, Zhang YL, Yang XL, Bi HL, Li HH. Administration of ubiquitin-activating enzyme UBA1 inhibitor PYR-41 attenuates angiotensin II-induced cardiac remodeling in mice. Biochem Biophys Res Commun. 2018 Oct 20;505(1):317-324. doi: 10.1016/j.bbrc.2018.09.100. Epub 2018 Sep 22. PMID: 30249396. 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.|
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Note: PYR-41, in solution, may exist as a mixture of E- and Z- isomers in a ratio of 1:1. HPLC may show two peaks.