ACT-132577

Details:

Common name :N - [5 - (4 - bromine phenyl) - 6 - [2 - [(5 - bromine - 2 - pyrimidine base) oxygen radicals) ethoxy] - 4 - pyrimidine base] amino sulfonamide

English name :ACT - 132577(Aprocitentan )
CAS number: 1103522-45-7
Molecular weight :546.19300

Molecular formula C16H14Br2N6O4S

Physical activity
Description ACT-132577 is the main active metabolite of macitentan and is a dual ETA/ETB inhibitor.
Related category
Signaling Pathway >> G protein-coupled receptors /G proteins >> Endothelin receptors
Research Areas >> Cardiovascular diseases
In vitro studies of ACT-132577 achieved complete inhibition of ET-1 on intracellular calcium increase induced by non-recombinant cells (primary human lung smooth muscle cells and rat aortic smooth muscle cell line A10 and mouse fibroblast cell line 3T3) [1].
In vivo studies ACT-132577 has a distribution volume greater than plasma volume and a longer half-life than its parent compound in rats [1]. In rat plasma, the average recovery of ACT-132577 ranges from 82.6% to 90.6%, and the matrix effect of ACT-132577 in rat plasma ranges from 101.4% to 115.2% [2].
Kinase assay Competitive binding assay was performed in 200μL50mMTris/HCl buffer (pH 7.4) consisting of 25mM MnCl 2,1mM EDTA, 0.5% (w/v) bovine serum albumin (V part) and (2-aminoethyl) benzene sulfonyl fluoride in 50μg/ mL 4-polypropylene microtitration plates. Membranes containing 0.5μg protein (ETA) or 0.2μg protein (ETB) were incubated at room temperature for 2 hours with 16pM 125I-ET-1 (8000cpm) and an unlabeled test compound in increasing concentrations. Maximum and minimum binding were determined in samples without and without 100nM unlabeled ET-1. After incubation for 2 hours, the membrane was filtered onto a filter plate containing a GF/C filter. Add 50 µL scintillation mixture to each hole and count the filter plate in the microplate counter. The test compound was dissolved, diluted, and added to the assay in dimethyl sulfoxide. The final concentration of DSO was 2.5%, and it was found that it did not interfere with binding. The IC 50 value is calculated as the concentration of an antagonist that inhibits 50% ET-1 specific binding.