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Atrasentan
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Atrasentan图片
CAS NO:173937-91-2
包装与价格:
包装价格(元)
1 mg电议
5 mg电议
10 mg电议
25 mg电议
50 mg电议

产品名称
A-147627
(+)-A 127722
ABT-627
阿曲生坦
产品介绍
AtRasentan 是内皮素受体 (Endothelin Receptor) 拮抗剂,能够抑制 ETA的活性(IC50:0.0551 nM)。

产品描述

Atrasentan (ABT-627) is an endothelin receptor antagonist (IC50: 0.0551 nM for ETA).

体外活性

Atrasentan (0-50 μM) significantly inhibits LNCaP and C4-2b prostate cancer cell growth. ABT-627 in combination with Taxotere elicits a significantly greater loss of viable prostate cancer cells relative to either agent alone and shows a greater degree of down-regulation of the NF-κB DNA binding activity [2]. Atrasentan profoundly induces several CYPs and drug transporters. It is a moderate P-gp inhibitor (IC50: 15.1 μM in P388/dx cells) and a weak BCRP inhibitor (IC50: 59.8 μM in MDCKII-BCRP cells) [3].

体内活性

Atrasentan (3 mg/kg, p.o.) inhibits the pressor response induced by big endothelin-1 (1 nmol/kg) in pithed rats [1]. Aatrasentan (10 mg/kg, i.p.) inhibited the C4-2b tumor growth within the bone environment to some extent in the SCID-hu model [2].

激酶实验

Cells are incubated and treated with Atrasentan. They are then washed twice with PBS and lysed in ice-cold lysis buffer [20 mM Tris (pH 7.4), 150 mM NaCl, 1% Triton X-100, 1 mM EDTA, 1 mM EGTA, 2.5 mM sodium PPi, 1 mM β-glycerophosphate, 1 mM sodium orthovanadate, 1 μg/mL leupeptin, and 1 mM PMSF]. The extracts are centrifuged to remove cellular debris, and the protein content of the supernatants is determined using the bicinchoninic acid (BCA) protein assay reagent. Proteins (150 μg) are incubated with gentle rocking at 4°C overnight with immobilized Akt antibody cross-linked to agarose hydrazide beads. After the Akt is selectively immunoprecipitated from the cell lysates, the immunoprecipitated products are washed twice with lysis buffer and twice with kinase assay buffer [25 mM Tris (pH 7.5), 10 mM MgCl2, 5 mM β-glycerol phosphate, 0.1 mM sodium orthovanadate, 2 mM DTT] and then resuspended in 40 μL of kinase assay buffer containing 200 μM ATP and 1 μg GSK-3α/β fusion protein. The kinase assay reaction is allowed to proceed at 30°C for 30 min and stopped by the addition of Lamelli SDS sample buffer. Reaction products are resolved by 10% SDS-PAGE, followed by Western blotting with antiphosphorylated GSK-3α/β antibody. For analysis of the total amount of Akt, 40 μg of protein from the lysate samples are resolved by 10% SDS-PAGE, followed by Western blotting with anti-Akt antibody [2].

细胞实验

All three prostate cancer cell lines (LNCaP, C4-2b, and PC-3 cells) are seeded at a density of 3 × 10^3 cells per well in 96-well microtiter culture plates. After overnight incubation, the medium is removed and replaced with a fresh medium containing different concentrations of ABT-627 (0-50 μM) diluted from a 10-mM stock. After 72 h of incubation with the drug, 20 μL of MTT solution (5 mg/mL in PBS) is added to each well and incubated further for 2 h. Upon termination, the supernatant is aspirated and the MTT formazan formed by metabolically viable cells is dissolved in isopropanol (100 μL). The plates are mixed for 30 min on a gyratory shaker, and the absorbance is measured at 595 nm on a plate reader [2].

动物实验

YM598 (0.3, 1, and 3 mg/kg), atrasentan (0.3, 1, and 3 mg/kg), or 0.5% methylcellulose as vehicle is orally administered to rats with a dosing cannula. The dosing volume of the test substances and vehicle is set at 5 mL/kg. Approximately 20 min after administration of compounds, the rats are anesthetized with sodium pentobarbital, and then pithed and ventilated 30 min after dosing. Approximately 1 h after oral administration of compounds, big endothelin-1 (1 nmol/kg) is intravenously administered, and blood pressure is measured. In these two experiments, the dose of test compound that causes 50% inhibition (ID50) of the big endothelin-1-induced increase in diastolic blood pressure is determined by linear regression analysis [1].

Cas No.

173937-91-2

分子式

C29H38N2O6

分子量

510.62

别名

A-147627;(+)-A 127722;ABT-627;阿曲生坦

储存和溶解度

DMSO:Soluble
Powder: -20°C for 3 years
In solvent: -80°C for 2 years