ACT-132577

Despropyl Macitentan
An Antagonist of Endothelin Receptors
    Cat #: A-350
    Alternative Name Despropyl Macitentan
  • Lyophilized Powder
  • Bioassay Tested
  • Source Synthetic
    MW: 546.19
    Purity: >98%
    Effective concentration 1-100 µM.
      • ACT-132577
    Chemical name 5-(4-bromophenyl)-4-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-6-(sulfamoylamino)pyrimidine.
    Molecular formula C16H14Br2N6O4S.
    CAS No.: 1103522-45-7.
    PubChem CID 25099191
    Activity ACT-132577, a metabolite of macitentan, is a dual antagonist of ET-A and ET-B endothelin receptors, inhibiting binding of 125I-ET-1 to recombinant ET-A and ET-B receptors with IC50 values of 3.4 nM and 987 nM, respectively1.
      • Iglarz, M. et al. (2008) J. Pharmacol. Exp. Ther. 327, 736.
    Shipping and storage Shipped at room temperature. Product as supplied can be stored intact at room temperature for several weeks. For longer periods, it should be stored desiccated at -20°C.
    Solubility Soluble in DMSO with gentle warming. Centrifuge all products before use (10000 x g 5 min).
    Storage of solutions Up to three months at -20°C.
      • ACT-132577
        Alomone Labs ACT-132577 inhibits ET-B receptor-mediated Ca2+ mobilization in CHO cells.
        Dose-response plot of ACT-132577 (#A-350) inhibition of the ET-B receptor-mediated, endothelin-1-evoked Ca2+ mobilization (IC50 = 5.99 µM). Cells were loaded with Calcium 6 dye, incubated with ACT-132577, and stimulated with 30 nM endothelin-1 (EC80). Changes in intracellular Ca2+ levels were detected as changes in maximum relative fluorescence (RLU) using FLIPRTETRA™.
    References - Scientific background
      • ACT-132577 is an active metabolite of Macitentan that acts as an endothelin B (ET-B) and endothelin A (ET-A) receptor antagonist. ACT-132577 antagonizes the specific binding of endothelin-1 on membranes of cells overexpressing ET-A and ET-B receptors with IC50 values of 3.4 nM and 987 nM, respectively1. It also has the ability to reach full inhibition of intracellular Ca2+ increase induced by endothelin-1 on non-recombinant cells1.

        Endothelin receptors belong to the superfamily of G-protein coupled receptors and include two subtypes: ET-A and ET-B. ET-A receptors are predominantly expressed in peripheral tissues, especially in vascular smooth muscle tissues to mediate vasoconstriction. They are also present in several different regions of the brain. ET-B receptors play an important role in regulating renal function and blood pressure and are expressed in sensory nerves. They are mainly detected in medium- and large-sized cell bodies of human trigeminal ganglia.

        The ET-A receptor has high affinity for endothelin-1 and endothelin-2 and relatively low affinity for endothelin-3, while the ET-B receptor has high affinity for all endothelin isopeptides2,3.

    Target Endothelin receptors
    Last update: 19/08/2019

    ACT-132577 (#A-350) is a highly pure, synthetic, and biologically active compound.

    For research purposes only, not for human use