Macitentan

Short Summary : Endothelin (ET)(A) and ET(B) receptor antagonist

Category : GPCR/G protein|Endothelin Receptor

Purity : 0.98

CAS Number : 441798-33-0

Formula : C19H20Br2N6O4S

Molecular Weight : 588.27

SMILE : CCCNS(=O)(=O)NC1=C(C(=NC=N1)OCCOC2=NC=C(C=N2)Br)C3=CC=C(C=C3)Br

Solubility : >21.2mg/mL in DMSO

Storage : Store at -20°C

Description : Macitentan is a new dual ETA/ETB endothelin (ET) receptor antagonist, with mean IC50 values of 0.5 0.2 nM (n= 17) to inhibit the binding of 125I-ET-1 to recombinant ETA receptors, and of 391182 nM (n= 17) for ETB receptors in Chinese hamster ovary cells [1].
ETA and ETB are ET receptors, both of them mediate the detrimental actions of ET-1, and dual blockade of them may be necessary [1].
In microsomal membranes of human-ETA and ETB-overexpressing Chinese hamster ovary cells, macitentan inhibited the binding between 125I-ET-1 and recombinant ETA receptors, with a mean IC50 value of 0.5 0.2 nM (n= 17). The mean IC50 value for ETB receptors was 391182 nM (n= 17). Macitentan completely inhibited the effect that ET-1 increased intracellular calcium in non-recombinant cells [1].
Intravenous administrated macitentan had a volume of distribution largely exceeding plasma volume and a terminal half-life of 2 h in rats. Macitentan was hence metabolized to its major and the only circulating metabolite, a dual ET receptor antagonist, ACT-132577. ACT-132577 also had a volume of distribution greater than the plasma volume. It showed a longer half-life than macitentan in rats. In rat, multiple oral dosing of macitentan at a dose of 10 mg/kg led to 4 to 5-fold higher exposure levels of ACT-132577 than those of the parent compound [1].
Reference: [1]. Marc Iglarz, Christoph Binkert, Keith Morrison, et al. Pharmacology of Macitentan, an Orally Active Tissue-Targeting Dual Endothelin Receptor Antagonist. Journal of Pharmacology and Experimental Therapeutics, 2008, 327:736-745.

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