PYR-41

製品コードS7129 バッチS712902

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₁₇H₁₃N₃O₇

分子量

371.3

CAS No.

418805-02-4

Solubility (25°C)*

体外

DMSO

74 mg/mL (199.29 mM)

Water

Insoluble

Ethanol

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension

CMC-NA

≥5mg/ml

Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	PYR-41 is the first cell-permeable inhibitor of ubiquitin-activating enzyme E1, with no activity at E2. PYR-41 induce apoptosis.
in vitro	PYR-41 (50 μM) inhibits activity of ubiquitin-activating enzyme E1 by over 90%. This compound could be a target for nucleophilic attack and potentially reacts with the active site cysteine of E1. It efficiently blocks cyclin E degradation. This chemical 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. It increases total sumoylation in cells and in cell harboring temperature-sensitive E1. It is able to inhibit both proteasome-dependent and proteasome-independent activities of ubiquitylation. This compound (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. It inhibits degradation of p53 and activates the transcriptional activity of p53, which enable its differentially killing transformed p53-expressing cells. ^[1] It blocks ubiquitination reactions but paradoxically leads to the accumulation of high MW ubiquitinated proteins. This compound also has equal or greater inhibitory activity against several deubiquitinases (DUBs) in intact cells and purified USP5 in vitro. It also mediates cross-linking of specific protein kinases (Bcr-Abl, Jak2) to inhibit their signaling activity. ^[1]

製品説明

PYR-41 is the first cell-permeable inhibitor of ubiquitin-activating enzyme E1, with no activity at E2. PYR-41 induce apoptosis.

in vitro

PYR-41 (50 μM) inhibits activity of ubiquitin-activating enzyme E1 by over 90%. This compound could be a target for nucleophilic attack and potentially reacts with the active site cysteine of E1. It efficiently blocks cyclin E degradation. This chemical 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. It increases total sumoylation in cells and in cell harboring temperature-sensitive E1. It is able to inhibit both proteasome-dependent and proteasome-independent activities of ubiquitylation. This compound (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. It inhibits degradation of p53 and activates the transcriptional activity of p53, which enable its differentially killing transformed p53-expressing cells. ^[1] It blocks ubiquitination reactions but paradoxically leads to the accumulation of high MW ubiquitinated proteins. This compound also has equal or greater inhibitory activity against several deubiquitinases (DUBs) in intact cells and purified USP5 in vitro. It also mediates cross-linking of specific protein kinases (Bcr-Abl, Jak2) to inhibit their signaling activity. ^[1]

プロトコル(参考用のみ)

キナーゼアッセイ	ubiquitylation reaction assay
キナーゼアッセイ	Rabbit or mouse E1 (~250 ng) is incubated with ^32P-ubiquitin in 1 譺eaction 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.

参考

https://pubmed.ncbi.nlm.nih.gov/17909057/
https://pubmed.ncbi.nlm.nih.gov/21621524/

カスタマーフィードバック

: Data from [Data independently produced by , , Nanoscale, 2016, 8: 18740-18750]

: Data from [Data independently produced by , , Neoplasia, 2017, 19(4):346-353]

: Data from [Data independently produced by , , J Virol, 2017, 91(5)]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

SAMD9 senses cytosolic double-stranded nucleic acids in epithelial and mesenchymal cells to induce antiviral immunity [ Nat Commun, 2025, 16(1):3756]	PubMed: 40263291
Glutathione reductase underlies the stability of mutant p53 by antagonizing protein glutathionylation [ Redox Biol, 2025, 81:103522]	PubMed: 39983342
TLR4 endocytosis and endosomal TLR4 signaling are distinct and independent outcomes of TLR4 activation [ EMBO Rep, 2025, 10.1038/s44319-025-00444-2]	PubMed: 40204912
Engineered a dual-targeting HA-TPP/A nanoparticle for combination therapy against KRAS-TP53 co-mutation in gastrointestinal cancers [ Bioact Mater, 2024, 32:277-291]	PubMed: 37876556
ER Stress-Activated HSF1 Governs Cancer Cell Resistance to USP7 Inhibitor-Based Chemotherapy through the PERK Pathway [ Int J Mol Sci, 2024, 25(5)2768]	PubMed: 38474017
IE1 of Human Cytomegalovirus Inhibits Necroptotic Cell Death via Direct and Indirect Modulation of the Necrosome Complex [ Viruses, 2024, 16(2)290]	PubMed: 38400065
Precise pancreatic cancer therapy through targeted degradation of mutant p53 protein by cerium oxide nanoparticles [ J Nanobiotechnology, 2023, 21(1):117]	PubMed: 37005668
The Ubiquitin-Proteasome System Facilitates Membrane Fusion and Uncoating during Coronavirus Entry [ Viruses, 2023, 15(10)2001]	PubMed: 37896778
The Ubiquitin-Proteasome System Facilitates Membrane Fusion and Uncoating during Coronavirus Entry [ Viruses, 2023, 15(10)2001]	PubMed: 37896778
Proteasomal and autophagy-mediated degradation of mutp53 proteins through mitochondria-targeting aggregation-induced-emission materials [ Acta Biomater, 2022, S1742-7061(22)00458-5]	PubMed: 35931280

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。