Antibodies
PYR-41
- 貨號 Cat. No.
- S7129
- 規格 Size
- 10mgã€25mg
- 品牌 Brand
- Selleckchem
Description
PYR-41
Catalog No.S7129
PYR-41 is the first cell-permeable inhibitor of ubiquitin-activating enzyme E1, with no activity at E2.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | PYR-41 is the first cell-permeable inhibitor of ubiquitin-activating enzyme E1, with no activity at E2. | |||||
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| Targets | ubiquitin-activating enzyme E1 | |||||
| IC50 | <10 μM [1] | |||||
| In vitro | PYR-41 (50 μM) inhibits activity of ubiquitin-activating enzyme E1 by over 90%. PYR-41 could be a target for nucleophilic attack and potentially reacts with the active site cysteine of E1. PYR-41 efficiently blocks cyclin E degradation. PYR-41 decreases the level of E1fUb thioesters in cells with a IC50 of between 10 and 25 μM, and prevents proteasome inhibitor–induced accumulation of ubiquitylated proteins. PYR-41 increases total sumoylation in cells and in cell harboring temperature-sensitive E1. PYR-41 is able to inhibit both proteasome-dependent and proteasome-independent activities of ubiquitylation. PYR-41 (50 μM) attenuates 1 ng/mL IL-1α-mediated nuclear factor-κB activation by >60% through preventing the downstream ubiquitylation and proteasomal degradation of IκBα. PYR-41 inhibits degradation of p53 and activates the transcriptional activity of p53, which enable its differentially killing transformed p53-expressing cells. [1] PYR-41 blocks ubiquitination reactions but paradoxically leads to the accumulation of high MW ubiquitinated proteins. PYR-41 also has equal or greater inhibitory activity against several deubiquitinases (DUBs) in intact cells and purified USP5 in vitro. PYR-41 also mediates cross-linking of specific protein kinases (Bcr-Abl, Jak2) to inhibit their signaling activity.[1] | |||||
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| Features | ||||||
Protocol(Only for Reference)
Kinase Assay:
| ubiquitylation reaction assay | Rabbit or mouse E1 (~250 ng) is incubated with 32P-ubiquitin in 1 èºeaction buffer [50 mM Tris (pH 7.4), 0.2 mM ATP, 0.5 mM MgCl2] at room temperature for 15 min. In some experiments, the His-tagged mouse E1 is bound to TALON cobalt affinity resin before carrying out incubations and reactions. Mouse E1 and 32P-ubiquitin are added to the beads in 1 ?reactionbuffer and incubated as for E1 reactions. Samples are heated in nonreducing SDS-PAGE sample buffer and resolved by SDS-PAGE. Thioesters with ubiquitin are visualized by Storm PhosphoImager. |
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References
Chemical Information
| Molecular Weight (MW) | 371.3 |
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| Formula | C17H13N3O7 |
| CAS No. | 418805-02-4 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 74 mg/mL (199 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | <1 mg/mL (<1 mM) | ||
| * <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. | |||
| Chemical Name | Benzoic acid, 4-[4-[(5-nitro-2-furanyl)methylene]-3,5-dioxo-1-pyrazolidinyl]-, ethyl ester |
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