1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAtrasentan hydrochlorideCat. No.: HY-15403ACAS No.: 195733-43-8Synonyms: ABT-627 (hydrochloride); (+)-A 127722 (hydrochloride); A-147627 (hydrochloride)分式: CHClNO分量: 547.08作靶點(diǎn): Endothelin Receptor作通路: GPCR/G Protein儲(chǔ)存式: Powder -

2、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 : 33.3 mg/mL (60.87 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 1.8279 mL 9.1394 mL 18.2789 mL5 mM 0.3656 mL 1.8279 mL 3.6558 mL10 mM 0.1828 mL 0.9139 mL 1.8279 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度

3、，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)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： 0.5% CMC-Na/saline waterSolubility: 0.75 mg/mL (1.37 mM); Clear solution; Need ultrasonic and warming1/3 Master of Small Molecule

4、s 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 Atrasentan hydrochloride種有效的內(nèi)素受體 (endothelin receptor) 拮抗劑，抑制 ETA 的活性，IC50值為 0.0551 nM。IC50 & Target IC50: 0.055 nM (ETA)體外研究 Atrasentan (ABT-627, 0-50 M) significantly inhibits LNCaP and C4-2b prostate cancer cell growth. ABT-627in conbination with Taxote

5、re elicits a significantly greater loss of viable prostate cancer cells relative to eitheragent alone and shows greater degree of down-regulation of the NF-B DNA binding activity 2. Atrasentanprofoundly induces several CYPs and drug transporters (e.g. 12-fold induction of CYP3A4 at 50 M). It is amod

6、erate P-gp inhibitor (IC50 in P388/dx cells=15.11.6 M) and a weak BCRP inhibitor (IC50 in MDCKII-BCRP cells=59.811 M) 3.體內(nèi)研究 Atrasentan (3 mg/kg, p.o.) inhibits the pressor response induced by big endothelin-1 (1 nmol/kg) in pithedrats 1. Aatrasentan (ABT-627, 10 mg/kg, i.p.) as well as Taxotere alo

7、ne inhibited the C4-2b tumor growthwithin the bone environment to some extent in the SCID-hu model 2.PROTOCOLKinase Assay 2 Cells are incubated and treated with Atrasentan. They are then washed twice with PBS and lysed in ice-coldlysis buffer 20 mM Tris (pH 7.4), 150 mM NaCl, 1% Triton X-100, 1 mM E

8、DTA, 1 mM EGTA, 2.5 mM sodiumPPi, 1 mM -glycerophosphate, 1 mM sodium orthovanadate, 1 g/mL leupeptin, and 1 mM PMSF. Theextracts are centrifuged to remove cellular debris, and the protein content of the supernatants is determinedusing the bicinchoninic acid (BCA) protein assay reagent. Proteins (15

9、0 g) are incubated with gentle rockingat 4C overnight with immobilized Akt antibody cross-linked to agarose hydrazide beads. After the Akt isselectively immunoprecipitated from the cell lysates, the immunoprecipitated products are washed twice withlysis buffer and twice with kinase assay buffer 25 m

10、M Tris (pH 7.5), 10 mM MgCl2, 5 mM -glycerolphosphate, 0.1 mM sodium orthovanadate, 2 mM DTT and then resuspended in 40 L of kinase assaybuffer containing 200 M ATP and 1 g GSK-3/ fusion protein. The kinase assay reaction is allowed toproceed at 30C for 30 min and stopped by the addition of Lamelli

11、SDS sample buffer. Reaction products areresolved by 10% SDS, followed by Western blotting with antiphosphorylated GSK-3/ antibody. Foranalysis of the total amount of Akt, 40 g of protein from the lysate samples are resolved by 10% SDS-PAGE, followed by Western blotting with anti-Akt antibody.MCE has

12、 not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 2 All three prostate cancer cell lines (LNCaP, C4-2b, and PC-3 cells) are seeded at a density of 3 103 cellsper well in 96-well microtiter culture plates. After overnight incubation, the medium is remo

13、ved and replacedwith a fresh medium containing different concentrations of ABT-627 (0-50 M) diluted from a 10-mM stock.After 72 h of incubation with drug, 20 L of MTT solution (5 mg/mL in PBS) are added to each well andincubated further for 2 h. Upon termination, the supernatant is aspirated and the

14、 MTT formazan formed bymetabolically viable cells is dissolved in isopropanol (100 L). The plates are mixed for 30 min on a gyratoryshaker, and the absorbance is measured at 595 nm on a plate reader.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Ma

15、ster of Small Molecules 您邊的抑制劑師www.MedChemEAnimal YM598 (0.3, 1, and 3 mg/kg), atrasentan (0.3, 1, and 3 mg/kg), or 0.5% methyl cellulose as vehicle is orallyAdministration 1 administered to rats with a dosing cannula. Dosing volume of the test substances and vehicle is set at 5mL/kg. Approximately

16、20 min after administration of compounds, the rats are anesthetized with sodiumpentobarbital, and then pithed and ventilated 30 min after dosing. Approximately 1 h after oral administrationof compounds, big endothelin-1 (1 nmol/kg) is intravenously administered, and blood pressure is measured.In the

17、se two experiments, the dose of test compound that cause 50% inhibition (ID50) of the big endothelin-1-induced increase in diastolic blood pressure is determined by linear regression analysis.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) E

18、ur J Pharmacol. 2019 Mar 12;852:142-150. Mol Immunol. 2019 Jul 18;114:10-18. J Vet Intern Med. 2015 Nov;29(6):1584-94. Department Veterinary Clinical Medicine. University of Illinois. 2015.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Yuyama H, et al. Superiority of YM598 over atrasentan as a selective endothelin ETA receptor antagonist. Eur J Pharmacol. 2004 Sep13;498(1-3):171-7.2