| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| Other Sizes |
| Targets |
Aprocitentan D4 targets the same receptors as its unlabeled parent drug. Aprocitentan is a dual ETA/ETB antagonist with pA2 values of 6.7 and 5.5, and IC50 values of 3.4 nM and 987 nM, respectively. By blocking endothelin receptors, it inhibits endothelin-mediated vasoconstriction and smooth muscle proliferation.
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| ln Vitro |
The ET-1-induced rise in intracellular calcium in non-recombinant cells (primary human lung smooth muscle cells, rat aortic smooth muscle cell line A10, and mouse fibroblast cell line 3T3) is entirely inhibited by aproticitentan (ACT-132577) [1].
Aprocitentan D4 is primarily used as an analytical internal standard rather than for its pharmacological activity. Aprocitentan is a major active metabolite of Macitentan, a dual ETA/ETB antagonist. The compound is used in LC-MS/MS methods for the quantification of Aprocitentan and Macitentan in biological matrices. The deuterium labeling provides a mass shift for accurate quantification. |
| ln Vivo |
Aprocitentan (ACT-132577) has a longer half-life than its parent chemical and a volume of distribution larger than rats' plasma volumes [1]. The average recovery of Aprocitentan (ACT-132577) in rat plasma ranged from 82.6% to 90.6%, whereas its matrix effect in rat plasma varied from 101.4% to 115.2% [2].
Aprocitentan D4 is used in pharmacokinetic studies as an internal standard for the quantification of Aprocitentan. Aprocitentan is a major active metabolite of Macitentan, a dual ETA/ETB antagonist. The deuterium-labeled compound can be co-administered with unlabeled drug to study absorption, distribution, metabolism, and excretion. It is used in bioequivalence studies and method validation. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for Aprocitentan D4 are typically performed as part of analytical method validation. The compound is used as an internal standard in LC-MS/MS assays for the quantification of Aprocitentan. It is dissolved in an appropriate solvent and spiked into biological matrices at known concentrations. Calibration curves are generated by plotting the peak area ratio of Aprocitentan to Aprocitentan D4 against the concentration of Aprocitentan.
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| Cell Assay |
For in vitro cell-based assays, Aprocitentan D4 can be used in studies investigating Aprocitentan's receptor antagonism, though its primary use is as an analytical internal standard. Cells expressing ETA or ETB receptors are cultured and treated with the compound. Receptor antagonism is confirmed by its ability to block endothelin-induced signaling. However, due to its role as an internal standard, it is more frequently used in analytical quantification.
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| Animal Protocol |
In vivo animal studies with Aprocitentan D4 are primarily pharmacokinetic. The compound is administered orally to rodents, and blood samples are collected at predetermined time points. Plasma concentrations of both labeled and unlabeled Aprocitentan are analyzed by LC-MS/MS using Aprocitentan D4 as the internal standard. Pharmacodynamic effects can be evaluated in models of hypertension or pulmonary arterial hypertension.
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| ADME/Pharmacokinetics |
Aprocitentan D4 (CAS: 1103522-45-7) has a molecular weight of 546.19 g/mol and a molecular formula of C16H14Br2N6O4S. Synonyms: ACT-132577 D4. Related CAS: Aprocitentan D4. Appearance: solid powder. Storage: powder at -20°C. The compound is a tetra-deuterated form of Aprocitentan, a major active metabolite of Macitentan.
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| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation There is currently no information regarding the clinical use of apraciltan during lactation. Because apraciltan binds to plasma proteins at a rate exceeding 99%, its concentration in breast milk is likely to be low. However, its half-life is 41 hours, which may allow it to accumulate in the infant. Since there is currently no information regarding the use of apraciltan during lactation, alternative medications are recommended, especially for breastfed newborns or premature infants. ◉ Effects on Breastfed Infants No published information was found as of the revision date. ◉ Effects on Lactation and Breast Milk No published information was found as of the revision date. As a deuterium-labeled analog of a drug metabolite, Aprocitentan D4 is expected to have a similar toxicity profile to Aprocitentan, though toxicity studies are typically not performed on the labeled compound. Aprocitentan is generally well-tolerated, with common side effects including headache, peripheral edema, and nasopharyngitis. The compound is used in very small quantities as an analytical internal standard. |
| References |
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| Additional Infomation |
ACT-132577 belongs to the sulfonamide class of compounds, in which one amino group of the sulfonamide group is replaced by 5-(4-bromophenyl)-6-{2-[(5-bromopyrimidin-2-yl)oxy]ethoxy}pyrimidin-4-yl. It is the active metabolite of macitentan (an orphan drug for the treatment of pulmonary arterial hypertension, prepared by oxidative depropanolization). ACT-132577 has multiple functions, including antihypertensive activity, endothelin receptor antagonism, drug metabolism, and exogenous substance metabolism. It is an aromatic ether, an organic bromine compound, belonging to the pyrimidine and sulfonamide classes. Functionally, it is related to ethylene glycol. Apraceptan is currently being investigated in the clinical trial NCT03541174 (a study aimed at demonstrating the efficacy of apraceptan in treating refractory hypertension and further understanding its safety).
Drug Indications Treatment of hypertension Aprocitentan D4 (ACT-132577 D4) is the tetra-deuterated form of Aprocitentan, a major active metabolite of Macitentan, a dual ETA/ETB antagonist. Aprocitentan has pA2 values of 6.7 and 5.5, and IC50 values of 3.4 nM and 987 nM for ETA and ETB, respectively. The labeled compound is used as an internal standard for analytical and pharmacokinetic studies. It is not intended for therapeutic use. |
| Molecular Formula |
C₁₆H₁₀D₄BR₂N₆O₄S
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|---|---|
| Molecular Weight |
550.22
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| Exact Mass |
543.916
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| CAS # |
1103522-45-7
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| Related CAS # |
Aprocitentan-d4
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| PubChem CID |
25099191
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| Appearance |
White to off-white solid powder
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| LogP |
4.385
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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 |
8
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| Heavy Atom Count |
29
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| Complexity |
597
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| Defined Atom Stereocenter Count |
0
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| SMILES |
0
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| InChi Key |
DKULOVKANLVDEA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H14Br2N6O4S/c17-11-3-1-10(2-4-11)13-14(24-29(19,25)26)22-9-23-15(13)27-5-6-28-16-20-7-12(18)8-21-16/h1-4,7-9H,5-6H2,(H2,19,25,26)(H,22,23,24)
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| Chemical Name |
5-(4-bromophenyl)-4-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-6-(sulfamoylamino)pyrimidine
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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 |
| 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) |
DMSO : ~25 mg/mL (~45.77 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.58 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.58 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8175 mL | 9.0873 mL | 18.1745 mL | |
| 5 mM | 0.3635 mL | 1.8175 mL | 3.6349 mL | |
| 10 mM | 0.1817 mL | 0.9087 mL | 1.8175 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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