Bosentan hydrate

Ro 47-0203
An Antagonist of Endothelin Receptors
  • New
Cat #: B-170
Sizes: 25 mg, 50 mg, 100 mg, 250 mg
  • Lyophilized Powder
  • Bioassay Tested
  • Shipped at Room Temp.
  • Source: Synthetic
    MW: 569.63 Da.
    Purity >98%.
    Effective concentration 0.1-100 nM.
    Structure
    Chemical name 4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-pyrimidin-2-ylpyrimidin-4-yl]benzenesulfonamide;hydrate.
    Molecular formula C27H29N5O6S · H2O.
    CAS number 157212-55-0.
    Activity

    Bosentan is a dual antagonist of the ET-A and ET-B Endothelin receptors, shown to inhibit Endothelin-1 radioligand binding to ET-A and ET-B with Ki of 4.7 nM and 95 nM, respectively. in vitro it competitively inhibits aortic contractions induced by Endothelin-1 and tracheal contractions induced by Sarafotoxin S6C with pA2 of 7.2 and 6.0, respectively1. Bosentan is orally bioavailable and active in vivo2.

    Storage before reconstitution Product before reconstitution should be stored at +4oC.
    Reconstitution Soluble in DMSO. Centrifuge all products before use (10000 x g 5 min).
    Storage after reconstitution Up to three months at -20°C.
    Our bioassay
    Alomone Labs Bosentan hydrate inhibits ET-A receptor-mediated Ca2+ mobilization in CHO cells.
    Dose response curve of Bosentan hydrate (#B-170) inhibition of ET-A receptor-mediated, Endothelin-1-evoked Ca2+ mobilization. IC50 was determined at 8.18 nM. Cells were loaded with Calcium 6 dye, incubated with Bosentan hydrate, and stimulated with 15 nM Endothelin-1 (EC80). Changes in intracellular Ca2+ levels were detected as changes in maximum relative fluorescence (RLU) using FLIPRTETRA™.
    References
    1. Clozel, M. et al. (1994) J. Pharmacol. Exp. Ther270, 228.
    2. Iglarz, M. et al. (2014) Life Sci. 118, 333.
    3. Saeki, T. et al. (1991) Biochem. Biophys. Res. Commun. 179, 286.
    4. Xie, C. and Wang, D.H. (2009) Hypertension 54, 1298.
    Target: Endothelin receptors
    Last update: 08/02/2018

    Bosentan hydrate (Ro 47-0203), is a synthetic nonpeptide compound that acts as an antagonist of endothelin A (ET-A) and endothelin B (ET-B) receptors. Bosentan hydrate is obtained by structural optimization of Ro 46-2005, a less potent ET-A/ET-B antagonist that is orally bioavailable and active in vivo. Bosentan hydrate competitively inhibits the specific binding of radioligand endothelin-1 to ET-A receptors in human smooth muscle cells with Ki value of 4.7 nM, and to ET-B receptors in human placenta with a Ki of 95 nM1. Bosentan may be used as a useful drug in the management of clinical disorders associated with vasoconstriction1,2.

    ET-A receptors are predominantly detected in peripheral tissues, especially in vascular smooth muscle tissues where they mediate vasoconstriction. They are also expressed in several 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 present in medium- and large-sized cell bodies of human trigeminal ganglia.

    ET-A receptor has high affinity for endothelin-1 and endothelin-2 and relatively low affinity for endothelin-3, while ET-B receptor has high affinity equally for all endothelin isopeptides3,4.

    Alomone Labs is pleased to offer Bosentan hydrate (#B-170).

    For research purposes only, not for human use