Macitentan

製品コードS8051 バッチS805101

印刷

化学情報

Chemical Structure Synonyms ACT 064992 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C19H20Br2N6O4S
分子量 588.27 CAS No. 441798-33-0
Solubility (25°C)* 体外 DMSO 100 mg/mL (169.98 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Macitentan is an orally active, non-peptide, dual ETA/ETB (endothelin) receptor antagonist with IC50 of 0.5 nM/391 nM.
in vitro Macitentan achieves full inhibition of intracellular calcium increase induced by ET-1 on primary human pulmonary smooth muscle cells with approximate IC50 of 1 nM. Macitentan inhibits ET-1-induced contractions on isolated rat aortic rings or S6c-induced contractions on isolated rat tracheal rings with pA2 of 7.6 and 5.9, respectively. [1]
in vivo Macitentan administered to normotensive rats, increases plasma ET-1 concentration, which occurred at a 10-fold lower dose than with bosentan. Macitentan dose-dependently decreases mean arterial blood pressure in hypertensive DOCA-salt rats with a maximal effect of -26 mm Hg at a dose of 10 mg/kg and a ED50 of 1mg/kg. At the maximal effective dose, the duration of the blood pressure response to Macitentan is approximately 40 hr. Macitentan orally administrated dose-dependently preventes the development of pulmonary hypertension and the development of right ventricle hypertrophy with a maximal efficacy of 30 mg/kg/day in monocrotaline rat model of pulmonary hypertension. Chronic oral administration of Macitentan at 30 mg/kg/day significantly improves the 42-day survival in monocrotaline rats (83 vs 50% survival in macitentan vs vehicle; 66% reduction of mortality at 42 days). [1] Macitentan (30 mg/kg/day) treated for 24 h partially prevents the development of renal vasoconstriction and increases renal blood flow in streptozotocin-induced diabetic rat model. Macitentan increases glomerular filtration rate and decreases filtration fraction, and attenuates vascular and tubulo-interstitial lesions and also glomerular damage. [1] Macitentan (25 mg/kg/day, p.o.) attenuates the increase of renal, cardiac and retinal ET-1, TGF-β1, VEGF, FN, EDB+FN, collagenα-I(IV) mRNA expression along with increased FN, collagen protein and NF-κB activation induced by type 2 diabetes in db/db mice. Macitentan also ameliorates mesangial expansion, cardiac dysfunction and the increased expression of ANP and BNP in these diabetic mice. [2] Macitentan (100mg/kg) treatment combined with paclitaxel (5 mg/kg) reduced tumor incidence (5/9 vs 9/9 of paclitaxel along) and further reduces tumor weight (median [range]: 0.1 vs 0.4 g of paclitaxel along) and incidences of ascites (0/9 vs 4/9 of paclitaxel along) in SKOV3ip1 ovarian cancer model when compared with paclitaxel alone. Macitentan plus paclitaxel inhibits the phosphorylation of ETRs and suppresses the survival pathways of tumor cells by decreasing the levels of pVEGFR2, pAkt, and pMAPK. Macitentan enhances effects of paclitaxel on tumor cells dividing (Brud+ cells: 18.5 vs 30.8 of paclitaxel along) and apoptosis (TUNEL+ cells: 195 vs 150 of paclitaxel along). [3]

プロトコル(参考用のみ)

キナーゼアッセイ Binding assay
The cDNAs for human ET-A and ET-B receptors are cloned, sequenced, and stably overexpressed in Chinese hamster ovary cells. Membranes are prepared from these cells. The competition binding assay is performed in 200 μL of 50 mM Tris/HCl buffer, pH 7.4, including 25 mM MnCl2, 1 mM EDTA, 0.5% (w/v) bovine serum albumin (fraction V), and 50 μg/mL 4-(2-aminoethyl)benzenesulfonyl fluoride in polypropylene microtiter plates. Membranes containing 0.5 μg of protein (ET-A) or 0.2 μg of protein (ET-B) are incubated for 2 h at room temperature with 16 pM 125I-ET-1 (8000 cpm) and increasing concentrations of unlabeled test compounds. Maximal and minimal binding is determined in samples without and with 100 nM unlabeled ET-1, respectively. After 2 h of incubation, the membranes are filtered onto filter plates containing GF/C filters. To each well, 50 μL of scintillation cocktail is added, and the filter plates counted in a microplate counter. Test compounds are dissolved, diluted, and added to the assay in dimethyl sulfoxide. The final concentration of dimethyl sulfoxide in the assay is 2.5%, which is found not to interfere with the binding.

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

MiRNAs in Systemic Sclerosis Patients with Pulmonary Arterial Hypertension: Markers and Effectors [ Biomedicines, 2022, 10(3)629] PubMed: 35327430
Evaluation of CML TKI Induced Cardiovascular Toxicity and Development of Potential Rescue Strategies in a Zebrafish Model [ Front Pharmacol, 2021, 12:740529] PubMed: 34733159
Novel Targets in a High-Altitude Pulmonary Hypertension Rat Model Based on RNA-seq and Proteomics [ Front Med (Lausanne), 2021, 8:742436] PubMed: 34805208
Targeting the Endothelin-1 Receptors Curtails Tumor Growth and Angiogenesis in Multiple Myeloma [ Front Oncol, 2020, 10:600025] PubMed: 33489901
Role of endothelin-1 clearance in the haemodynamic responses to endothelin-1 in the pulmonary and hindquarter vasculature of anaesthetised rats. [ Eur J Pharmacol, 2019, 855:124-136] PubMed: 31063771
Macitentan, a double antagonist of endothelin receptors, efficiently impairs migration and microenvironmental survival signals in chronic lymphocytic leukemia [ Oncotarget, 2017, 8(52):90013-90027] PubMed: 29163807
Distortion of KB estimates of endothelin-1 ETA and ETB receptor antagonists in pulmonary arteries: Possible role of an endothelin-1 clearance mechanism [ Pharmacol Res Perspect, 2017, 5(6)] PubMed: 29226623

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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