| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
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.) ( PYR-41 in solution may exist as a mixture of E- and Z- isomers. HPLC may show two peaks depending on conditions).
| Targets |
E1(IC50: < 10 μM)
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|---|---|
| ln Vitro |
PYR-41 not only prevents ubiquitylation but also raises total sumoylation in cells. PYR-41 reduces nuclear factor-κB activation mediated by cytokines. Additionally, PYR-41 stops IκBα from being ubiquitylated downstream and from being broken down by proteases. Moreover, PYR-41 stimulates this tumor suppressor's transcriptional activity and prevents p53 from being degraded[1]. The accumulation of ubiquitinated proteins is promoted by PYR-41 (50 μM).After 4 hours, Z138 cells exhibit a concentration-dependent (10-50 μM) decrease in DUB activity due to PYR-41. Potent inhibition of USP5 DUB activity is observed even at the lowest concentration (10 μM) of PYR-41. Potently (10-50 μM), PYR-41 inhibits the activity of multiple DUBs, which have been identified as USP9x, USP5, USP14, UCH37, and UCH-L3. When DTT and PYR-41 are administered together to Z138 cells, the accumulation of ubiquitinated proteins is totally eliminated[2].
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| Enzyme Assay |
For 15 minutes, 32P-ubiquitin is incubated at room temperature in 1× reaction buffer (50 mM Tris (pH 7.4), 0.2 mM ATP, and 0.5 mM MgCl2) with rabbit or mouse E1 (apper 250 ng). Before conducting incubations and reactions, the His-tagged mouse E1 is bound to TALON cobalt affinity resin in certain experiments. Beads in 1× reaction buffer are mixed with mouse E1 and 32P-ubiquitin, and they are then incubated similarly to E1 reactions. Samples are resolved by SDS-PAGE after being heated in nonreducing SDS-PAGE sample buffer. Storm PhosphoImager visualizes thioesters that have ubiquitin.
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| References |
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| Additional Infomation |
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.
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| Molecular Formula |
C17H13N3O7
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|---|---|
| Molecular Weight |
371.30102
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| Exact Mass |
371.075
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| Elemental Analysis |
C, 54.99; H, 3.53; N, 11.32; O, 30.16
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| CAS # |
418805-02-4
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| Related CAS # |
418805-02-4
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| PubChem CID |
5335621
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| Appearance |
Brown solid powder
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| Density |
1.5±0.1 g/cm3
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| Index of Refraction |
1.652
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| LogP |
2.87
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
27
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| Complexity |
664
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1C(=C([H])C([H])=C1/C(/[H])=C1/C(N([H])N(C/1=O)C1C([H])=C([H])C(C(=O)OC([H])([H])C([H])([H])[H])=C([H])C=1[H])=O)[N+](=O)[O-]
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| InChi Key |
ARGIPZKQJGFSGQ-LCYFTJDESA-N
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| 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-
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| Chemical Name |
ethyl 4-(4-((5-nitrofuran-2-yl)methylene)-3,5-dioxopyrazolidin-1-yl)benzoate
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| Synonyms |
PYR41; PYR 41; PYR-41.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : 46~74 mg/mL ( 123.89~199.29 mM )
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.73 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2% DMSO + 30% PEG300 + 5% Tween80 + 63% ddH2O: 2mg/ml (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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