Bosentan 

Bosentan is a competitive and dual antagonist of endothelin-1 (ET) for the ET_A and ET_B receptors with K_i of 4.7 nM and 95 nM in human SMC, respectively.

Ki: 4.7 nM (ET_A receptor, in human SMC), 95 nM (ET_A receptor, in human SMC)^[1]

Bosentan (BOS) competitively and specifically antagonizes binding of ¹²⁵I-labelled ET-1 to ET_A receptors on human smooth muscle cells (SMC) and ET_B receptors on human placenta cells. The in vitro binding affinity of Bosentan to ET_A receptors on human SMC is 4.7 nM and to ET_B receptors on human SMC or placenta cells is 41 or 95 nM. Bosentan has 67-fold greater selectivity for ET_A than ET_B receptors (mean IC₅₀=7.1 vs 474.8 nM) in an in vitro ¹²⁵I-labeling assay^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In hypertensive rats, Macitentan 30 mg/kg further decreases mean arterial blood pressure (MAP) by 19 mm Hg when given on top of Bosentan 100 mg/kg. Conversely, Bosentan given on top of Macitentan fails to induce an additional MAP decrease. In pulmonary hypertensive rats, Macitentan 30 mg/kg further decreases mean pulmonary artery pressure (MPAP) by 4 mm Hg on top of Bosentan, whereas a maximal effective dose of Bosentan given on top of Macitentan does not cause any additional MPAP decrease^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

551.61

C₂₇H₂₉N₅O₆S

147536-97-8

Solid

White to off-white

O=S(NC1=NC(C2=NC=CC=N2)=NC(OCCO)=C1OC3=CC=CC=C3OC)(C4=CC=C(C(C)(C)C)C=C4)=O

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

• [1]. Dhillon S, et al. Bosentan: a review of its use in the management of mildly symptomatic pulmonary arterial hypertension. Am J Cardiovasc Drugs. 2009;9(5):331-50.  [Content Brief]

  [2]. Akamata K, et al. Bosentan reverses the pro-fibrotic phenotype of systemic sclerosis dermal fibroblasts via increasing DNA binding ability of transcription factor Fli1. Arthritis Res Ther. 2014 Apr 3;16(2):R86.  [Content Brief]

  [3]. Iglarz M, et al. Comparison of pharmacological activity of macitentan and bosentan in preclinical models of systemic and pulmonary hypertension. Life Sci. 2014 Nov 24;118(2):333-9.  [Content Brief]

  [4]. Son GY, et al. Endothelin Regulates Porphyromonas gingivalis-Induced Production of Inflammatory Cytokines. PLoS One. 2016 Dec 28;11(12):e0167713.  [Content Brief]