Home Ubiquitin E1 Activating inhibitor - Apoptosis related activator PYR-41 For research use only.

PYR-41

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

PYR-41 Chemical Structure

PYR-41 Chemical Structure

CAS No. 418805-02-4

Purity & Quality Control

PYR-41 Related Products

Signaling Pathway

E1 Activating Signaling Pathways

E1 Activating Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HI5 insect cells Function assay 30 min Inhibition of N-terminal GST-tagged human UAE-catalyzed UAE-Ub thioester intermediate formation expressed in HI5 insect cells after 30 mins by immunoblotting analysis, IC50=10 μM 23360215
HI5 insect cells Function assay Inhibition of N-terminal GST-tagged human UAE-catalyzed [32P]-AMP:[a-32P]-ATP exchange expressed in HI5 insect cells by TLC analysis, IC50=6.4 μM 23360215
insect cells Function assay Inhibition of mouse recombinant His6-tagged UAE-catalyzed UAE-Ub thioester intermediate formation expressed in insect cells by SDS-PAGE analysis, IC50=10 μM 23360215
Click to View More Cell Line Experimental Data

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
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]

Chemical Information & Solubility

Molecular Weight 371.3 Formula

C17H13N3O7
CAS No. 418805-02-4 SDF Download PYR-41 SDF
Smiles CCOC(=O)C1=CC=C(C=C1)N2C(=O)C(=CC3=CC=C(O3)[N+](=O)[O-])C(=O)N2
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 74 mg/mL ( (199.29 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

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.

Handling Instructions

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