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Macitentan Endothelin Receptor antagonist

Name: Macitentan
SKU: S8051
Availability: InStock
Rating: 5 (10 reviews)

Cat.No.S8051

Macitentan is an orally active, non-peptide, dual ETA/ETB (endothelin) receptor antagonist with IC50 of 0.5 nM/391 nM.

Chemical Structure

Molecular Weight: 588.27

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.98%

99.98

Related Targets	Adrenergic Receptor AChR 5-HT Receptor Histamine Receptor Dopamine Receptor Ras GPR GluR Prostaglandin Receptor CXCR Adenosine Receptor P2 Receptor CCR Angiotensin Receptor Hedgehog/Smoothened S1P Receptor PKA Cannabinoid Receptor cAMP Glucagon Receptor SGLT Opioid Receptor Sigma Receptor PAR LTR Neurokinin Receptor Guanylate Cyclase PKG LPA Receptor OX Receptor
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Chemical Information, Storage & Stability

Molecular Weight	588.27	Formula	C₁₉H₂₀Br₂N₆O₄S	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	441798-33-0	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	ACT 064992			Smiles	CCCNS(=O)(=O)NC1=C(C(=NC=N1)OCCOC2=NC=C(C=N2)Br)C3=CC=C(C=C3)Br

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (169.98 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (8.50mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.830mg/ml (1.41mM)	Taking the 1 mL working solution as an example, add 50 μL of 16.6 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	ET-A ^[1] 0.5 nM ET-B ^[1] 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. This compound 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. This compound 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 this compound is approximately 40 hr. It 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 this chemical 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] This compound (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. It increases glomerular filtration rate and decreases filtration fraction, and attenuates vascular and tubulo-interstitial lesions and also glomerular damage. ^[1] This chemical (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. It also ameliorates mesangial expansion, cardiac dysfunction and the increased expression of ANP and BNP in these diabetic mice. ^[2] This compound (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. It plus paclitaxel inhibits the phosphorylation of ETRs and suppresses the survival pathways of tumor cells by decreasing the levels of pVEGFR2, pAkt, and pMAPK. This chemical 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]
References	[1] https://pubmed.ncbi.nlm.nih.gov/18780830/ [2] https://pubmed.ncbi.nlm.nih.gov/22525377/ [3] https://pubmed.ncbi.nlm.nih.gov/21403842/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT05731492	Recruiting	Arterial Hypertension Pulmonary	Actelion	March 14 2024	Phase 1
NCT05167825	Recruiting	Pulmonary Arterial Hypertension	Janssen Pharmaceutical K.K.	November 14 2022	Phase 3
NCT05433675	Completed	Healthy	Actelion	June 22 2022	Phase 1
NCT05392530	Completed	Healthy	Actelion	May 25 2022	Phase 1
NCT05373108	Completed	Cardiac Allograft Vasculopathy	University of California Los Angeles\|American Heart Association\|Janssen LP	May 19 2022	Phase 4

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