Find Ubiquitin-Activating Enzyme, Cell-Permeable Inhibitor, Pyr-41 Inhibitor on Industry Directory, Reliable Manufacturer/Supplier/Factory from China.

Inquiry Basket (0)
Home > Products > Ubiquitin > E1 Activating Inhibitor > PYR-41 418805-02-4

PYR-41 418805-02-4

Product Description

.cp_wz table {border-top: 1px solid #ccc;border-left:1px solid #ccc; } .cp_wz table td{border-right: 1px solid #ccc; border-bottom: 1px solid #ccc; padding: 5px 0px 0px 5px;} .cp_wz table th {border-right: 1px solid #ccc;border-bottom: 1px solid #ccc; padding: 5px 0px 0px 5px;}


Molecular Weight: 371.3 PYR-41 is the first Cell-Permeable Inhibitor of Ubiquitin-Activating Enzyme E1, with no activity at E2.


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. 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.

Protocol(Only for Reference)

Kinase Assay:


[1]

ubiquitylation reaction assay Rabbit or mouse E1 (~250 ng) is incubated with 32P-ubiquitin in 1 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.


Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)


Species Baboon Dog Monkey Rabbit Guinea pig Rat Hamster Mouse
Weight (kg) 12 10 3 1.8 0.4 0.15 0.08 0.02
Body Surface Area (m2) 0.6 0.5 0.24 0.15 0.05 0.025 0.02 0.007
Km factor 20 20 12 12 8 6 5 3

Animal A (mg/kg) = Animal B (mg/kg) multiplied by Animal B Km
Animal A Km



For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) × mouse Km(3) = 11.2 mg/kg
rat Km(6)










Chemical Information




Molecular Weight (MW) 371.3
Formula

C17H13N3O7

CAS No. 418805-02-4

Storage 3 years -20℃Powder
6 months-80℃in solvent (DMSO, water, etc.)
Synonyms



Solubility (25°C) * In vitro DMSO 74 mg/mL (199.29 mM)
Water <1 mg/mL (
Ethanol <1 mg/mL (





Chemical Name Benzoic acid, 4-[4-[(5-nitro-2-furanyl)methylene]-3,5-dioxo-1-pyrazolidinyl]-, ethyl ester










Contact us if you need more details on 418805-02-4 PYR-41. We are ready to answer your questions on packaging, logistics, certification or any other aspects about 418805-02-4、PYR-41 418805-02-4. If these products fail to match your need, please contact us and we would like to provide relevant information.

Product Categories : Ubiquitin > E1 Activating Inhibitor