Home GPCR & G Protein Endothelin Receptor antagonist Macitentan For research use only.

Macitentan

Synonyms: ACT 064992

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

Macitentan Chemical Structure

Macitentan Chemical Structure

CAS No. 441798-33-0

Purity & Quality Control

Macitentan Related Products

Signaling Pathway

Endothelin Receptor Signaling Pathways

Endothelin Receptor Signaling Pathway

Biological Activity

Description Macitentan is an orally active, non-peptide, dual ETA/ETB (endothelin) receptor antagonist with IC50 of 0.5 nM/391 nM.
Targets
ET-A [1] ET-B [1]
0.5 nM 391 nM
In vitro
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
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]
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

Chemical Information & Solubility

Molecular Weight 588.27 Formula

C19H20Br2N6O4S
CAS No. 441798-33-0 SDF Download Macitentan SDF
Smiles CCCNS(=O)(=O)NC1=C(C(=NC=N1)OCCOC2=NC=C(C=N2)Br)C3=CC=C(C=C3)Br
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (169.98 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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