Sibrafiban

Names

[ Name ]:
Sibrafiban

[Synonym ]:
Xubix
UNII-YUE443B0NF
Sibrafiban
Ro 48-3657

Biological Activity

[Description]:

Sibrafiban (RO 48-3657) is the orally active, nonpeptide, double-prodrug of Ro 44-3888 and a selective glycoprotein IIb/IIIa receptor antagonist. Sibrafiban inhibits platelet aggregation[1][2][3].

[Related Catalog]:

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Cytoskeleton >> Integrin

[Target]

Glycoprotein IIb/IIIa receptor[1]

[In Vitro]

The effects of site occupancy by Sibrafiban on platelet activation are assessed using P-selectin expression, fibrinogen binding and microaggregate formation. Sibrafiban inhibits ADP and TRAP-stimulated fibrinogen binding and microaggregate formation in a concentration-dependent manner, whereas P-selectin expression is relatively unaltered. A decrease in site occupancy from peak to trough of Sibrafiban does not result in increased activation of platelets[3].

[In Vivo]

The effects of Ro 44-3888 on the platelet aggregation response to ADP (17 μmol) and on cutaneous bleeding times is determined in 8 rhesus monkeys given Sibrafiban 0.25 mg/kg/day or 0.5 mg/kg/day orally for 8 days. The maximum inhibition of ex vivo platelet aggregation and prolongation of bleeding time by Ro 44-3888 are dose dependent[1].

[References]

[1]. M Dooley, et al. Sibrafiban. Drugs. 1999 Feb;57(2):225-30; discussion 231-2.

[2]. B Wittke, et al. Pharmacokinetics and pharmacodynamics of sibrafiban alone or in combination with ticlopidine and aspirin. Br J Clin Pharmacol. 2000 Mar;49(3):231-9.

[3]. Jeffrey T Billheimer, et al. Effects of glycoprotein IIb/IIIa antagonists on platelet activation: development of a transfer method to mimic peak to trough receptor occupancy. Thromb Res. 2002 Sep 15;107(6):303-17.

Chemical & Physical Properties

[ Density]:
1.33g/cm3

[ Molecular Formula ]:
C₂₀H₂₈N₄O₆

[ Molecular Weight ]:
420.46000

[ Exact Mass ]:
420.20100

[ PSA ]:
143.55000

[ LogP ]:
1.49920

[ Index of Refraction ]:
1.598