Catalog No.S7129

PYR-41 Chemical Structure

Molecular Weight(MW): 371.3

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

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  • (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.

    Nanoscale, 2016, 8: 18740-18750. PYR-41 purchased from Selleck.

    (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.

    Neoplasia, 2017, 19(4):346-353. PYR-41 purchased from Selleck.

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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.
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]


Solubility (25°C)

In vitro DMSO 74 mg/mL (199.29 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents individually and in order:
2% DMSO+30% PEG 300+5% Tween 80+ddH2O

* 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 Information

Molecular Weight 371.3


CAS No. 418805-02-4
Storage powder
in solvent
Synonyms N/A

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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E1 Activating Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID