Sitaxentan sodium

Names

[ Name ]:
Sitaxentan sodium

[Synonym ]:
Thelin
Sodium (4-chloro-3-methyl-1,2-oxazol-5-yl)({2-[(6-methyl-1,3-benzodioxol-5-yl)acetyl]-3-thienyl}sulfonyl)azanide
3-Thiophenesulfonamide, N-(4-chloro-3-methyl-5-isoxazolyl)-2-[2-(6-methyl-1,3-benzodioxol-5-yl)acetyl]-, sodium salt (1:1)
Sitax
Sitaxsentan sodium
Sitaxentan sodium [USAN]
Sitaxentan sodium
Sitaxsentan (sodium)

Biological Activity

[Description]:

Sitaxsentan (sodium) is an orally active, highly selective antagonist of endothelin A receptors.

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> Endothelin Receptor

Research Areas >> Cardiovascular Disease

[In Vitro]

Sitaxsentan and Bosentan attenuate NTCP transport at higher concentrations, and inhibit human hepatic transporters, which provides a potential mechanism for the increased hepatotoxicity observed for these agents in the clinical setting. Only sitaxsentan decreased OATP transport (52%)[1]. Sitaxsentan and sitaxsentan combined with sildenafil completely prevent the increased expressions of endothelin-1 and of the ETB receptor. Sitaxsentan alone partially restores the expressions of BMPR-1A and BMPR-2. The combination of sildenafil and sitaxsentan further restores the expressions of BMPR-1A and BMPR-2, which remaines, however, decreased compared with controls[3].

[In Vivo]

Sitaxsentan (5 mg/kg infused iv 10 min prior to onset of hypoxia) completely blocks hypoxia-induced vasoconstriction and this group does not differ from air controls. Oral administration of sitaxsentan, significantly attenuates the increase in MPAP, while the administration of sitaxsentan to rats exposed to normal oxygen levels is without effect on MPAP[2]. Sitaxsentan alone limits shunt-induced increase in MT. Sitaxsentan combined with sildenafil more effectively prevents this remodeling, which, however, tends to remain increased compared with controls[3].

[Animal admin]

After an initial 2-week period of hypoxic exposure (10% O2) sitaxsentan (15 or 30 mg/kg body weight per day in the drinking water) is administered for 4 weeks during continuous exposure to hypoxia. At the conclusion of the 4 week period of hypoxia, femoral and pulmonary arterial cannulation and measurement of MPAP, MSAP, and HR are performed.

[References]

[1]. Hartman JC, et al. Evaluation of the endothelin receptor antagonists ambrisentan, darusentan, bosentan, and sitaxsentan as substrates and inhibitors of hepatobiliary transporters in sandwich-cultured human hepatocytes. Can J Physiol Pharmacol. 2010 Jun;88

[2]. Tilton RG, et al. Attenuation of pulmonary vascular hypertension and cardiac hypertrophy with sitaxsentan sodium, an orally active ET(A) receptor antagonist. Pulm Pharmacol Ther. 2000;13(2):87-97.

[3]. Rondelet B, et al. Sildenafil added to sitaxsentan in overcirculation-induced pulmonary arterial hypertension. Am J Physiol Heart Circ Physiol. 2010 Oct;299(4):H1118-23. Epub 2010 Aug 6.

[Related Small Molecules]

Chemical & Physical Properties

[ Molecular Formula ]:
C₁₈H₁₄ClN₂NaO₆S₂

[ Molecular Weight ]:
476.88600

[ Exact Mass ]:
475.98800

[ PSA ]:
135.56000

[ LogP ]:
4.90080

[ Appearance of Characters ]:
white to beige

[ Storage condition ]:
room temp

[ Water Solubility ]:
H2O: soluble10mg/mL (clear solution)

Safety Information

[ RIDADR ]:
NONH for all modes of transport

[ RTECS ]:
XN0296600

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