PYR-41

Catalog No.S7129 Batch:S712901

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Technical Data

Formula

C17H13N3O7
Molecular Weight 371.3 CAS No. 418805-02-4
Solubility (25°C)* In vitro DMSO 74 mg/mL (199.29 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description PYR-41 is the first cell-permeable inhibitor of ubiquitin-activating enzyme E1, with no activity at E2. PYR-41 induce apoptosis.
Targets
Ubiquitin-activating Enzyme E1 [1]
(Cell-free assay)
<10 μM
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]

Protocol (from reference)

References

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

Customer Product Validation

(D) Ubiquitination level of Htt protein was detected by immunoprecipitation with the GFP antibody and western blotting with the ubiquitin antibody from GFP-Htt(Q74)/PC12 cells treated as (C). Total Htt protein level served as the loading control. (E) GFP-Htt(Q74)/PC12 cells were treated as (C).Soluble Htt protein was detected by western blotting and quantified. Mean ± SEM, n = 5, ***p < 0.001 compared to the control group. (F) GO binding assay of GFP-Htt(Q74)/PC12 cells treated with GO, followed by Western blotting (left panel) with the ubiquitin antibody and Coomassie Brilliant Blue staining (right panel). L is the lysate before precipitation, while S and P were the supernatant and the pellet, respectively, after the precipitation. (G) Ubiquitination levels of Htt protein in supernatant lysate prepared from GO treated GFP-Htt(Q74)/PC12 cells with or without GO binding for 30 min.

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

(A) Serum-restricted A431 cells were pretreated with PYR-41 for 30 minutes prior to stimulation with EGF for 1 hour. Cells were lysed and incubated with UBA01 ubiquitin binding beads. Samples were separated by SDS-PAGE and analyzed by western blot for PD-L1. (B) WCL was analyzed for total PD-L1 levels and activated EGFR levels (p-EGFR). Tubulin was used as a loading control.

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

(E) Intensities of protein bands were determined by densitometric analysis. Relative cellular levels of β2M were normalized to GAPDH levels and are presented relative to the levels in mock-infected and DMSO-treated cells (set as 1). Data are presented as means ± SD from three independent experiments. **, P < 0.01 between the indicated groups analyzed by Student

Data from [ , , J Virol, 2017, 91(5) ]

Treatment with PYR-41 or thalidomide abrogates the endosomal recruitment of Sec61α. Murine bone marrow-derived DC (cultured for 4 d) conferred thalidomide (30 μM), PYR-41 (5 μM), or DMSO treatment prior to ovalbumin (50 μg/ml) or PBS pulse. The relocation of Sec61α from endoplasmic reticulum to endosomes was determined by confocal microscope by Rab5, calnexin, and Sec61α antibody staining. The expressions of Rab5/Sec61α and calnexin/Sec61α in the cells which are corresponding to the colocalized cells were shown (c). Nuclei were counterstained with DAPI (blue). Original magnification, ×600. Rab5: early endosome marker; calnexin: endoplasmic reticulum marker.

Data from [ , , J Immunol Res, 2018, 2018:5070573 ]

Selleck's PYR-41 has been cited by 36 publications

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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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