iloprost

Iloprost is a synthetic analogue of prostacyclin PGI2. Iloprost commonly employed in the treatment of peripheral vascular disease and also indicated in the treatment of patients affected by systemic sclerosis (SSc) in the presence of severe Raynaud's phen

Iloprost is a second generation structural analog of prostacyclin (PGI2) with about ten-fold greater potency than the first generation stable analogs, typified by carbaprostacyclin. Iloprost binds with equal affinity to the recombinant human IP and EP1 receptors with a Ki value of 11 nM. Most preparations of iloprost contain 16(S) and 16(R) stereoisomers. 16(R)-Iloprost inhibits platelet aggregation with an IC50 value of 65 nM.

Iloprost is a second generation structural analog of prostacyclin (PGI2) with about ten-fold greater potency than the first generation stable analogs, typified by carbaprostacyclin. Iloprost binds with equal affinity to the recombinant human IP and EP1 receptors with a Ki value of 11 nM. Most preparations of iloprost contain 16(S) and 16(R) stereoisomers. 16(S)-Iloprost potently inhibits platelet aggregation with an IC50 value of 3.5 nM.

Epoxyeicosatrienoic acids (EETs), such as 11(12)-EET and 14(15)-EET, are cytochrome P450 metabolites of arachidonic acid that have been identified as endothelium-derived hyperpolarizing factors with vasodilator activity. 14,15-EE-5(Z)-E is a structural analog of 14,15-epoxyeicosatrienoic acids (14,15-EET) that antagonizes EET-induced relaxation of vascular smooth muscle. Relaxation of U46619-constricted bovine arteries by 14,15-EET could be inhibited approximately 80% by 14,15-EE-5(Z)-E at a concentration of 10 μM. 14,15-EE-5(Z)-E does not appear to antagonize nitric oxide- or iloprost-mediated vascular relaxation.

sulotroban is a TXA2 receptor antagonist that acts synergistically with iloprost to inhibit TXA2-dependent platelet activation.

RO1138452 (CAY10441) is a selective and orally bioavailable antagonist of prostacyclin receptor (pKi: 8.3). It antagonizes the carbaprostacyclin-induced activation of human neuroblastoma adenylate cyclase, blocking cyclic AMP accumulation in a dose-dependent manner. Likewise, it inhibits the binding of tritiated iloprost to rodent neuroblastoma cells with a Ki of about 1.5 nM. At levels between 2-20 mg/kg in rats, CAY10441 shows significant analgesic activity in standard antinociceptive assays [1].

BMY-42393 is orally active and selective platelet aggregation inhibitor. BMY-42393 is also a prostacyclin partial agonist that inhibited ADP, collagen and thrombin-induced platelet aggregation (IC50 range 0.3 - 2.0 microM). BMY-42393 stimulated platelet adenylate cyclase activity (EC50 = 25 nM). Platelets treated with BMY 42393 showed an elevation of cAMP levels and activation of cAMP-dependent protein kinase. BMY 42393 also inhibited thrombin-induced elevation of intracellular free calcium. BMY 42393 competed for radiolabeled iloprost and PGE1 binding to platelet membranes (IC50; 170 nM and 130 nM, respectively).