| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
Endothelin Receptors Type A (ETA) and Type B (ETB). Macitentan D4 is a dual antagonist of ETA and ETB receptors. It binds to ETA with high affinity (IC50 = 0.5 nM) and to ETB with lower affinity (IC50 = 391 nM) in radioligand binding assays. It inhibits endothelin-1 (ET-1)-induced intracellular calcium increases in human pulmonary arterial smooth muscle cells.
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|---|---|
| ln Vitro |
Macitentan potently inhibits ET-1-induced contraction of isolated rat aortic rings (pA2 = 7.6 for ETA). It also inhibits sarafotoxin S6c-induced contractions of isolated rat tracheal rings (pA2 = 5.9 for ETB), demonstrating functional antagonism at both receptor subtypes. In human pulmonary arterial smooth muscle cells (HPASMCs), macitentan inhibits ET-1-induced Ca2+ increases with an IC50 of 0.9 nM.
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| ln Vivo |
Oral administration of macitentan (30 mg/kg/day) prevents the development of pulmonary hypertension and right ventricle hypertrophy in a rat model induced by monocrotaline. It also decreases mean arterial blood pressure in hypertensive DOCA-salt rats (ED50 = 1 mg/kg). Macitentan increases plasma ET-1 concentrations in normotensive rats, consistent with receptor blockade. In a streptozotocin-induced diabetic rat model, macitentan reduces vascular and tubulointerstitial lesions and glomerular damage.
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| Enzyme Assay |
Radioligand binding assays are performed using membrane preparations from CHO cells expressing recombinant human ETA or ETB receptors. Membranes (20-40 microg protein) are incubated with [¹2⁵I]-ET-1 as the radioligand and varying concentrations of macitentan D4 in 50 mM Tris-HCl buffer (pH 7.4) containing 0.5% BSA for 120 minutes at 25degC. Nonspecific binding is determined with 100 nM unlabeled ET-1. Bound and free ligands are separated by filtration through GF/C filters, and radioactivity is measured with a gamma counter.
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| Cell Assay |
Human pulmonary arterial smooth muscle cells (HPASMCs) are cultured in SmBM-2 medium supplemented with 5% FBS. Cells are seeded in 96-well plates and loaded with the calcium-sensitive fluorescent dye Fluo-4 AM (5 microM) for 60 minutes at 37degC. After dye loading, varying concentrations of macitentan D4 are added, followed by stimulation with 10 nM ET-1. Intracellular Ca2+ levels are measured immediately by fluorescence (excitation at 494 nm, emission at 516 nm) using a plate reader. IC50 values are calculated from the inhibition of the ET-1-induced calcium response.
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| Animal Protocol |
Male Sprague-Dawley rats (200-250 g) with monocrotaline (MCT)-induced pulmonary hypertension are used. MCT (60 mg/kg) is injected subcutaneously on day 1. From day 1 to day 28, rats receive oral macitentan (30 mg/kg/day) or vehicle. On day 28, right ventricular systolic pressure (RVSP) is measured with a pressure transducer catheter inserted into the right ventricle. Heart and lungs are harvested for measurement of right ventricular hypertrophy index (RV/LV+S) and histological assessment of pulmonary vascular remodeling.
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| ADME/Pharmacokinetics |
Macitentan D4 serves as an internal standard for bioanalytical quantification. The parent drug macitentan has a terminal half-life of approximately 16 hours in humans, with steady-state achieved within 3-5 days. It is >99% protein bound and is primarily metabolized by CYP3A4 to its active metabolite, ACT-132577. The D4-labeled version is less toxic and has a longer half-life than the unlabeled parent drug in research settings.
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| Toxicity/Toxicokinetics |
Macitentan is generally well tolerated. The most common adverse reactions include headache, nasopharyngitis, anemia, and peripheral edema. Serious but rare side effects include hepatotoxicity and teratogenicity (pregnancy category X, causes fetal harm). Macitentan may also cause decreases in hemoglobin and hematocrit due to its vasodilatory effects.
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| References | |
| Additional Infomation |
Macitentan (Opsumit®) was FDA-approved in 2013 for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to reduce disease progression and hospitalization. The D4-labeled version is a research tool for internal standard use in LC-MS/MS bioanalysis, drug-drug interaction studies, and metabolite identification.
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| Molecular Formula |
C19H16D4BR2N6O4S
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|---|---|
| Molecular Weight |
592.297
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| Exact Mass |
589.988
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| CAS # |
1258428-05-5
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| Related CAS # |
Macitentan;441798-33-0
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| PubChem CID |
49849030
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.7±0.1 g/cm3
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| Boiling Point |
692.4±65.0 °C at 760 mmHg
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| Flash Point |
372.5±34.3 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.634
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| LogP |
5.41
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
32
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| Complexity |
642
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C([2H])(C([2H])([2H])OC1=NC=C(C=N1)Br)OC2=NC=NC(=C2C3=CC=C(C=C3)Br)NS(=O)(=O)NCCC
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| InChi Key |
JGCMEBMXRHSZKX-LZMSFWOYSA-N
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| InChi Code |
InChI=1S/C19H20Br2N6O4S/c1-2-7-26-32(28,29)27-17-16(13-3-5-14(20)6-4-13)18(25-12-24-17)30-8-9-31-19-22-10-15(21)11-23-19/h3-6,10-12,26H,2,7-9H2,1H3,(H,24,25,27)/i8D2,9D2
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| Chemical Name |
5-(4-bromophenyl)-6-[2-(5-bromopyrimidin-2-yl)oxy-1,1,2,2-tetradeuterioethoxy]-N-(propylsulfamoyl)pyrimidin-4-amine
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6883 mL | 8.4417 mL | 16.8833 mL | |
| 5 mM | 0.3377 mL | 1.6883 mL | 3.3767 mL | |
| 10 mM | 0.1688 mL | 0.8442 mL | 1.6883 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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