prostacyclin

5-cis Carbaprostacyclin, a stable analog of PGI2 and an isomer of carbaprostacyclin, is a weak inhibitor of human platelet aggregation with an IC50 of 2.8 μM compared to 0.3 μM for carbaprostacyclin. It is a much weaker effector of rabbit mesenteric artery relaxation with an EC50 of 104 μM compared to 5.9 μM for carbaprostacyclin and even antagonizes the adenylate cyclase activation induced by carbaprostacyclin.

13,14-dehydro-15-cyclohexyl Carbaprostacyclin is a chemically stable analog of PGI2. It inhibits the ADP-induced aggregation of human platelets with an ED50 of about 40 nM in PRP and 77 nM in washed platelets, which is comparable to the potency of carbaprostacyclin.

Girinimbine (Girinimbin) is a carbazole alkaloid isolated from the plants M. koenigii, M. koenigii, and Murraya koenigii. Girinimbine exhibits a wide range of biological effects, including apoptosis, antitrypanosomal, antiplatelet, antimicrobial, anti-inflammatory, antioxidant, and antitumor activities.

2-Acetylbenzoic acid is more potent than 2-propionyloxybenzoic acid in inhibiting platelet function and platelet prostaglandin (PG) synthesis although the potencies of these agents were comparable in inhibiting prostacyclin (PGI2) synthesis.

Bradykinin is an inflammatory mediator. It is a peptide that causes blood vessels to dilate (enlarge) via the release of prostacyclin, nitric oxide, and Endothelium-Derived Hyperpolarizing Factor. Bradykinin is a physiologically and pharmacologically active peptide of the kinin group of proteins, consisting of nine amino acids.

Prednicarbate (Hoe 777) is a Corticosteroid Hormone Receptor Agonist. Prednicarbate has antipruritic, anti-inflammatory, and vasoconstrictive properties. It also decreases the number of circulating lymphocytes by inhibiting the production of vasodilators such as nitric oxide and prostacyclin.

BAY 73-1449 is a potent and selective antagonist of the prostacyclin receptor (IC50 < 0.1 nM).

Carbacyclin, a PGI2 analog, is a prostacyclin (PGI2) receptor agonist and vasodilator with potent inhibitory platelet aggregation.

Epoprostenol sodium (Prostaglandin I2 sodium salt) is a short-acting vasodilator, a synthetic prostacyclin, and can be used to study pulmonary hypertension and congestive heart failure.

Tilsuprost is a stable prostacyclin analogue classified as an imino-prostacyclin derivative, exhibiting effective cytoprotective properties.

Taprostene sodium acts as a partial agonist of the prostacyclin (IP) receptor in the prostaglandin class. It interacts with Prostaglandin E2 (PGE2), ONO-AE1-259 (a selective EP2 agonist), and acetylcholine. Taprostene sodium offers significant cardioprotective effects.

AFP-07 is a highly selective and potent agonist. It was used for the prostacyclin receptor.

OP-2507, a prostacyclin agonist, is used potentially for the treatment of hepatic insufficiency and hypertension.

Beraprost is a stable prostacyclin analog.

Selexipag (ACT-293987)(NS-304) is prostacyclin receptor agonist that causes vasodilation in pulmonary vasculature and is used in the therapy of pulmonary arterial hypertension (PAH).

Nafazatrom is a pyrazolinone derivative and lipoxygenase inhibitor that increases endogenous prostacyclin (PGI2) and has experimental anticancer activity. Nafazatrom is also an antithrombotic drug that increases prostacyclin levels and reduces the inciden

RS-93427-007 is an orally active stable mimetic agent of prostacyclin for the study of mechanisms of atherogenesis.

TEI-9063 is a stable and highly specific prostacyclin analogue of prostacyclin receptor in mast cell tumor p-815 cells.

Palmitic acid-13C is intended for use as an internal standard for the quantification of palmitic acid by GC- or LC-MS. Palmitic acid is a 16-carbon saturated fatty acid. It comprises approximately 25% of human total plasma lipids.1 It increases protein levels of COX-2 in RAW 264.7 cells when used at a concentration of 75 μM.2 Palmitic acid is involved in the acylation of proteins to anchor membrane-bound proteins to the lipid bilayer.2,3,4,5,6 |1. Santos, M.J., López-Jurado, M., Llopis, J., et al. Influence of dietary supplementation with fish oil on plasma fatty acid composition in coronary heart disease patients. Ann. Nutr. Metab. 39(1), 52-62 (1995).|2. Lee, J.Y., Sohn, K.H., Rhee, S.H., et al. Saturated fatty acids, but not unsaturated fatty acids, induced the expression of cyclooxygenase-2 mediated through toll-like receptor 4. J. Biol. Chem. 276(20), 16683-16689 (2001).|3. Dietzen, D.J., Hastings, W.R., and Lublin, D.M. Caveolin is palmitoylated on multiple cysteine residues. Palmitoylation is not necessary for localization of caveolin to caveolae. J. Biol. Chem. 270(12), 6838-6842 (1995).|4. Robinson, L.J., and Michel, T. Mutagenesis of palmitoylation sites in endothelial nitric oxide synthase identifies a novel motif for dual acylation and subcellular targeting. Proc. Nat. Acad. Sci. USA 92(25), 11776-11780 (1995).|5. Topinka, J.R., and Bredt, D.S. N-terminal palmitoylation of PSD-95 regulates association with cell membranes and interaction with K+ channel Kv1.4. Neuron 20(1), 125-134 (1998).|6. Miggin, S.M., Lawler, O.A., and Kinsella, B.T. Palmitoylation of the human prostacyclin receptor. Functional implications of palmitoylation and isoprenylation. J. Biol. Chem. 278(9), 6947-6958 (2003).

Palmitic acid-13C is intended for use as an internal standard for the quantification of palmitic acid by GC- or LC-MS. Palmitic acid-13C contains 13C at the C2 position and has been used in the study of free fatty acid incorporation into phospholipid fatty acids in soil microbes.1 Palmitic acid is a 16-carbon saturated fatty acid. It comprises approximately 25% of human total plasma lipids.2 It increases protein levels of COX-2 in RAW 264.7 cells when used at a concentration of 75 μM.3 Palmitic acid is involved in the acylation of proteins to anchor membrane-bound proteins to the lipid bilayer.3,4,5,6,7 |1. Dippold, M.A., and Kuzyakov, Y. Direct incorporation of fatty acids into microbial phospholipids in soils: Position-specific labeling tells the story. Geochim. Cosmochim. Acta 174(1), 211-221 (2016).|2. Santos, M.J., López-Jurado, M., Llopis, J., et al. Influence of dietary supplementation with fish oil on plasma fatty acid composition in coronary heart disease patients. Ann. Nutr. Metab. 39(1), 52-62 (1995).|3. Lee, J.Y., Sohn, K.H., Rhee, S.H., et al. Saturated fatty acids, but not unsaturated fatty acids, induced the expression of cyclooxygenase-2 mediated through toll-like receptor 4. J. Biol. Chem. 276(20), 16683-16689 (2001).|4. Dietzen, D.J., Hastings, W.R., and Lublin, D.M. Caveolin is palmitoylated on multiple cysteine residues. Palmitoylation is not necessary for localization of caveolin to caveolae. J. Biol. Chem. 270(12), 6838-6842 (1995).|5. Robinson, L.J., and Michel, T. Mutagenesis of palmitoylation sites in endothelial nitric oxide synthase identifies a novel motif for dual acylation and subcellular targeting. Proc. Nat. Acad. Sci. USA 92(25), 11776-11780 (1995).|6. Topinka, J.R., and Bredt, D.S. N-terminal palmitoylation of PSD-95 regulates association with cell membranes and interaction with K+ channel Kv1.4. Neuron 20(1), 125-134 (1998).|7. Miggin, S.M., Lawler, O.A., and Kinsella, B.T. Palmitoylation of the human prostacyclin receptor. Functional implications of palmitoylation and isoprenylation. J. Biol. Chem. 278(9), 6947-6958 (2003).

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.

Prostacyclin (PGI2) is a cyclooxygenase metabolite with antithrombotic properties found in vascular endothelial cells. The half-life is short both in vivo and in vitro, ranging from 30 seconds to a few minutes. CG 4305 is a stable carbacyclic analog of PGI2 that inhibits ADP-induced platelet aggregation 25% at a concentration of 50 nM. Doses of 10 mg/kg (oral) or 1 mg/kg (intraduodenal) have been shown to prevent rabbit carotid artery thrombosis.

EDHF (endothelium-derived hyperpolarizing factor) is an unidentified mediator released from vascular endothelial cells in response to acetylcholine and bradykinin which is distinct from the NOS- (nitric oxide) and COX-derived (prostacyclin) vasodilators.[1],[2]Cytochrome P450 (CYP450) metabolism of polyunsaturated fatty acids produces epoxides such as (±)14(15)-EET which are prime candidates for the actual active mediator.[3] However, the CYP450 metabolites of eicosapentaenoic acid and docosahexaenoic acid have been little studied relative to arachidonate epoxygenase metabolites. (±)16(17)-EpDPA is the DHA homolog of (±)14(15)-EpETrE, derived via epoxidation of the 16,17-double bond of DHA. The EDHF activity of (±)16(17)-EpDPA has not yet been determined. The epoxygenase metabolites of DHA have also been detected in a mouse inflammation model.[4]