Sitaxsentan sodium salt

TBC-11251 sodium salt
A Potent and Selective Antagonist of Endothelin A Receptor
  • New
Cat #: S-185
Sizes: 10 mg, 25 mg, 50 mg, 100 mg
  • Lyophilized Powder
  • Bioassay Tested
  • Shipped at Room Temp.
  • Source: Synthetic
    MW: 476.88 Da.
    Purity >99%.
    Effective concentration 1-100 nM.
    Structure
    Chemical name (4-chloro-3-methyl-1,2-oxazol-5-yl)-[2-[2-(6-methyl-1,3-benzodioxol-5-yl)acetyl]thiophen-3-yl]sulfonylazanide sodium.
    Molecular formula C18H14ClN2NaO6S2.
    CAS number 210421-74-2.
    Activity Sitaxsentan is a potent and selective antagonist of ET-A Endothelin receptors, inhibiting Endothelin-1 radioligand binding to human ET-A and ET-B receptors with IC50 of 1.4 nM and 9.8 µM, respectively (a 7000-fold selectivity). in vitro, Sitaxsentan inhibits Endothelin-1 induced phosphoinositide turnover with a pAof 8.01. Sitaxsentan is orally bioavailable and active in vivo1,2.
    Storage before reconstitution Product before reconstitution should be stored at -20oC.
    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 Sitaxsentan sodium salt inhibits ETA receptor-mediated Ca2+ mobilization in CHO cells.
    Dose response curve of Sitaxsentan sodium salt (#S-185) inhibition of the ET-A receptor-mediated, Endothelin-1-evoked Ca2+ mobilization. IC50 was determined at 9.29 nM. Cells were loaded with Calcium 6 dye, incubated with Sitaxsentan sodium salt, 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. Wu, C. et al. (1997) J. Med. Chem. 40, 1690.
    2. Lepist, E.I. et al. (2014) PLoS One 9, e87548.
    3. Saeki, T. et al. (1991) Biochem. Biophys. Res. Commun. 179, 286.
    Target: ET-A receptors
    Last update: 08/02/2018

    Sitaxsentan, is a synthetic compound that acts as a potent and selective antagonist of ET-A endothelin receptors. Sitaxsentan is one of the most selective ET-A antagonists reported1. Sitaxsentan inhibits Endothelin-1 radioligand binding to human ET-A and ET-B receptors with IC50 of 1.4 nM and 9.8 µM, respectively1.

    In pulmonary arterial hypertension clinical trials, sitaxsentan was shown to improve exercise capacity, improve functional capacity, and delay clinical worsening. However, the compound shows high liver toxicity and is no longer used to treat hypertension2.

    Endothelin receptors include two subtypes: ET-A and ET-B. They are widely distributed in vascular and nonvascular tissues. ET-A receptors are predominantly detected in peripheral tissues, especially in vascular smooth muscle tissues to mediate vasoconstriction. They are also distributed in several regions of the brain.

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

    Alomone Labs is pleased to offer Sitaxsentan sodium salt (#S-185).

    For research purposes only, not for human use