Name: PYR-41
Brand: Selleck Chemicals
SKU: S7129
Availability: InStock
Rating: 5 (35 reviews)

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Quality Control

Batch: Purity: 99.88%

99.88

Related Targets	Proteasome E3 Ligase DUB p97 SUMO E2 conjugating
Other E1 Activating Inhibitors	MLN4924 (Pevonedistat) TAK-243 (MLN7243) ML792 TAS4464 COH000 DKM 2-93 Pevonedistat hydrochloride PYZD-4409 NEDD8 inhibitor M22

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Incubation Time	Activity Description
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
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
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
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

DMSO : 74 mg/mL (199.29 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
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.
Clear solution	2%DMSO 1 30%PEG300 2 5%Tween80 3 63%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	2.000mg/ml (5.39mM)	Taking the 1 mL working solution as an example, add 20 μL of 100 mg/ml clarified DMSO stock solution to 300 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify it; then continue to add 630 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
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.
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.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

%

% Tween 80

% ddH₂O

% DMSO

+

%

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	371.3	Formula	C₁₇H₁₃N₃O₇	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	418805-02-4	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CCOC(=O)C1=CC=C(C=C1)N2C(=O)C(=CC3=CC=C(O3)[N+](=O)[O-])C(=O)N2

Mechanism of Action

Targets/IC₅₀/Ki	Ubiquitin-activating Enzyme E1 (Cell-free assay) <10 μM
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. 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.
References	[1] https://pubmed.ncbi.nlm.nih.gov/17909057/ [2] https://pubmed.ncbi.nlm.nih.gov/21621524/

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PYR-41 E1 Activating inhibitor

Chemical Structure

Molecular Weight: 371.3