1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPYR-41Cat. No.: HY-13296CAS No.: 418805-02-4分式: CHNO分量: 371.3作靶點(diǎn): E1/E2/E3 Enzyme作通路: Metabolic Enzyme/Protease儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 46 mg/mL (123.89 mM)* means so

2、luble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.6932 mL 13.4662 mL 26.9324 mL5 mM 0.5386 mL 2.6932 mL 5.3865 mL10 mM 0.2693 mL 1.3466 mL 2.6932 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn) 請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前?qǐng)先配制澄清的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)

3、配，當(dāng)天使；澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.73 mM); Clear solutionBIOLOGICAL ACTIVITY1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemE物活性 PYR-41種選擇性，可透過(guò)細(xì)胞的泛素活化酶 E1 抑制劑，IC50 值于10 M，對(duì)E2和E3 本作。IC50 & Target IC50:

4、10 M (E1)體外研究 PYR-41 increases total sumoylation in cells in addition to blocking ubiquitylation. PYR-41 attenuates cytokine-mediated nuclear factor-B activation. PYR-41 also prevents the downstream ubiquitylation and proteasomaldegradation of IB. Furthermore, PYR-41 inhibits degradation of p53 and

5、activates the transcriptional activityof this tumor suppressor 1. PYR-41 (50 M) promotes accumulation of ubiquitinated proteins. PYR-41 causesa concentration-dependent (10-50 M) decline in DUB activity in Z138 cells after 4 h. PYR-41 potently inhibitsUSP5 DUB activity, even at the lowest concentrati

6、on (10 M). PYR-41 potently (10-50 M) inhibits the activityof various DUBs, determined to represent USP9x, USP5, USP14, UCH37 and UCH-L3. Co-treatment of Z138cells with DTT and PYR-41 completely abolishes the accumulation of ubiquitinated proteins 2.PROTOCOLKinase Assay 1 Rabbit or mouse E1 (apper 25

7、0 ng) is incubated with 32P-ubiquitin in 1 reaction 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 mouseE1 is bound to TALON cobalt affinity resin before carrying out incubations and reactions. Mouse E1 and 32P-ubiquitin are ad

8、ded to the beads in 1 reaction buffer and incubated as for E1 reactions. Samples are heatedin nonreducing SDSsample buffer and resolved by SDS. Thioesters with ubiquitin arevisualized by Storm PhosphoImager.MCE has not independently confirmed the accuracy of these methods. They are for reference onl

9、y.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Mol Cell Biol. 2018 Jul 16;38(15). pii: e00024-18. Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Yang Y, et al. Inhibitors of ubiquitin-activating enzyme (E1), a new class of potential cancer therapeutics. Cancer Res. 2007 Oct1;67(19):9472-81.2. Kapuria V, et al. Protein cross-linking as a novel mechanism of action of a ubiquitin-activating enzyme inhibitor with anti-tumor activity.Biochem Pharmacol. 2011 Aug 15;82(4):341-9.McePdfHeightCaution: Product has not been fully validated