PYR-41 418805-02-4
Product Description
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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]
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
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.
Chemical Information
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.
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 |
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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
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