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.
    Structure
    • 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.
    References-Activity
    1. 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.
    Our bioassay
    • 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
    1. Iglarz, M. et al. (2008) J. Pharmacol. Exp. Ther. 327, 736.
    2. Saeki, T. et al. (1991) Biochem. Biophys. Res. Commun. 179, 286.
    3. Xie, C. and Wang, D.H. (2009) Hypertension 54, 1298.
    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: 24/01/2020

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

    For research purposes only, not for human use
    Shipping and Ordering information