prostaglandin a2

PGA2 is a naturally occurring prostaglandin in gorgonian corals where it may function in self defense. It is generally not present in mammals. PGA2 has low biological potency in most bioassays, but it does show some antiviral/antitumor activity.[1] At a 25 uM concentration, PGA2 blocks the cell cycle progression of NIH 3T3 cells at the G1 and G2/M phase .[2] It has also been shown to act as a vasodilator with natriuretic properties.[3]

17-phenyl trinor-13,14-dihydro Prostaglandin A2 is a synthetic analog of prostaglandin with relatively unexplored biological activity. Similarly structured, particularly in its lower side chain, to the PGF2α analog latanoprost, which is an approved glaucoma treatment, this compound presents an interesting subject for further pharmaceutical research and potential therapeutic applications.

16,16-dimethyl PGA2 is a metabolism-resistant analog of PGA2 with a prolonged in vivo half-life. It inhibits the proliferation of Sendai virus in cultured African green monkey kidney cells by >90% at a concentration of 4 μg/ml. Daily infusion of 10 μg of 16,16-dimethyl PGA2 methyl ester into mice infected with influenza A virus increased survival by 40%. Similar treatment of mice inoculated with erythroleukemia cells delayed tumor growth and increased survival time.

8-iso Prostaglandin A2 is an isoprostane produced by the nonenzymatic oxidation of arachidonic acid.

17-Phenyl trinor prostaglandin A2 is a synthetic analog of prostaglandin [1].

Arbaprostil, a synthetic analog of prostaglandin E2 (PGE2) known as 15(R)-15-methyl prostaglandin E2, was developed for its cytoprotective activity. In the commercial production of bulk arbaprostil, one potential impurity is 15(R)-15-methyl Prostaglandin A2 (15(R)-15-methyl PGA2). The pharmacology and EP receptor binding affinity of 15(R)-15-methyl PGA2 have not been reported.

Cucumarioside A2-2 is a triterpene glycoside isolated from the Far-Eastern sea cucumber Cucumaria japonica, that exhibits antitumor activity.

Etodolac (AY-24236) inhibits the activity of cyclooxygenase I and II, thereby preventing the formation of prostaglandin which is involved in the induction of pain, fever, and inflammation. Etodolac is a pyranocarboxylic acid and non-steroidal anti-inflammatory drug (NSAID) with antipyretic and analgesic activities. It also inhibits platelet aggregation by blocking platelet cyclooxygenase and the subsequent formation of thromboxane A2.

Ozagrel (Domenan) is a selective thromboxane A(2) (TXA(2)) synthetase inhibitor with IC50 of 11 nM for rabbit platelet, used for the improvement of postoperative cerebrovascular contraction and accompanying cerebral ischaemia.

Ketoprofen (RP-19583) is a propionic acid derivative and nonsteroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic, and antipyretic effects. It inhibits cyclo-oxygenase I and II, decreasing the formation of prostaglandin and thromboxane precursors. This reduction in prostaglandin synthesis, mediated by prostaglandin synthase, is responsible for its therapeutic effects. Additionally, Ketoprofen decreases thromboxane A2 formation via thromboxane synthase, inhibiting platelet aggregation.

Ozagrel hydrochloride (OKY-046 HCl) is a selective thromboxane A(2) synthetase inhibitor used for the improvement of postoperative cerebrovascular contraction and accompanying cerebral ischaemia.

FCE-27262 is a prostaglandin H2/thromboxane A2 receptor antagonist.

L-670,596 is a thromboxane A2/prostaglandin endoperoxide receptor antagonist.

15(R)-Pinane thromboxane A2 is the (R)-epimer of pinane thromboxane A2 . 15(R)-PTA2 does not inhibit collagen-induced platelet aggregation (IC50s = 120-130 μM). It does not affect gastric tone in isolated rat gastric fundus when used at concentrations of 0.5 or 1.5 μg/ml and is less effective than PTA2 at inhibiting prostaglandin-induced contraction of isolated rat stomach muscle.

L 888607 Racemate is a selective antagonist of the prostaglandin D2 receptor subtype 1 (DP1) with Ki values of 132 nM and 17 nM for DP1 and the thromboxane A2 receptor (TP), respectively.

(R)-(+)-Bay-K-8644 is a Ca2+ channel and dihydropyridine agonist that inhibits Ba2+ currents (IBa), induces central respiratory depression in cats, and inhibits platelet activation through competitive antagonism of thromboxane A2-prostaglandin H2 receptors.

Mipitroban is a thromboxane A2/prostaglandin H2 antagonist.

FKGK 18 is an inhibitor of group VIA (GVIA) calcium-independent phospholipase A2 (iPLA2). It inhibits GVIA iPLA2 by 99.9% at 0.091 mole fraction in a mixed micelle activity assay and is selective for GVIA iPLA2 over GIVA cPLA2 and GV sPLA2 where it shows 80.8 and 36.8% inhibition, respectively. FKGK 18 inhibits iPLA2β activity in cytosolic extracts from INS-1 cells overexpressing iPLA2β (IC50 = ~50 nM) as well as iPLA2γ activity in mouse heart membrane fractions (IC50s = ~1-3 μM). It inhibits glucose-induced increases in prostaglandin E2 production and insulin secretion in human pancreatic islets when used at a concentration of 10 μM and inhibits thapsigargin-induced apoptosis in INS-1 cells overexpressing iPLA2β in a concentration-dependent manner. FKGK 18 (20 mg/kg, 3 times per week) reduces blood glucose levels in an intraperitoneal glucose tolerance test, decreases the incidence of diabetes, and increases serum insulin levels in non-obese diabetic (NOD) mice.

2-(E-2-decenoylamino)ethyl 2-(cyclohexylethyl) sulfide inhibits stress-induced ulcers by maintaining phospholipase A2 and prostaglandin E2 levels in rats subjected to water immersion-restrained stress-induced ulceration.

SQ 26655 is an antagonist of thromboxane A2/prostaglandin H2.

HA-29 is an inhibitor of thromboxane A2 and prostaglandin endoperoxide receptors.

LCB-2853 is a potent thromboxane A2 prostaglandin H2 (TXA2 PGH2) receptor antagonist with antiplatelet aggregation, antivasospasm, and antithrombotic effects.

Ifetroban (BMS-180291) sodium is an orally active thromboxane A2 (TXA2) and prostaglandin H2 (PGH2) receptor antagonist used to study myocardial ischemia, stroke, hypertension, thrombosis, and cardiomyopathy.

Arachidonic acid leelamide is a phospholipase A2 inhibitor. Phospholipase A is a hydrolase responsible for the release of arachidonic acid from the sn2 position of phospholipids. The released arachidonic acid is then converted to mediators of inflammation

Ono-3708 is a potent antagonist of the thromboxane A2/prostaglandin endoperoxide receptor in vitro and in vivo.

PGBx is a mixture of oligomers of PGB1 with a molecular weight of 1,000-1,500. It has antioxidant and free radical trapping activity that was first studied in isolated mitochondria.1 PGBx has anti-inflammatory and cytoprotective activity which may be attributed to inhibition of the 14 kDa sPLA2.2,3 At a dose of 1 mg/kg, PGBx significantly reduces the incidence of ulcers in rats.2References1. Polis, B.D., Polis, E., and Kwong, S. Protection and reactivation of oxidative phosphorylation in mitochondria by a stable free-radical prostaglandin polymer (PGBΧ). Proceedings of the National Academy of Sciences of the United States of America 76, 1598-1602 (1979).2. Kumashiro, R., Devlin, T.M., Kholoussy, A.M., et al. Prostaglandin BΧ in the prevention of stress ulcers in rats. International Surgery 70, 247-250 (1985).3. Franson, R.C., Rosenthal, M.D., and Regelson, W. Mechanism(s) of cytoprotective and anti-inflammatory activity of PGB1 oligomers: PGBx has potent anti-phospholipase A2 and anti-oxidant activity. Prostaglandins, Leukotrienes and Essential Fatty Acids 43, 63-70 (1991). PGBx is a mixture of oligomers of PGB1 with a molecular weight of 1,000-1,500. It has antioxidant and free radical trapping activity that was first studied in isolated mitochondria.1 PGBx has anti-inflammatory and cytoprotective activity which may be attributed to inhibition of the 14 kDa sPLA2.2,3 At a dose of 1 mg/kg, PGBx significantly reduces the incidence of ulcers in rats.2 References1. Polis, B.D., Polis, E., and Kwong, S. Protection and reactivation of oxidative phosphorylation in mitochondria by a stable free-radical prostaglandin polymer (PGBΧ). Proceedings of the National Academy of Sciences of the United States of America 76, 1598-1602 (1979).2. Kumashiro, R., Devlin, T.M., Kholoussy, A.M., et al. Prostaglandin BΧ in the prevention of stress ulcers in rats. International Surgery 70, 247-250 (1985).3. Franson, R.C., Rosenthal, M.D., and Regelson, W. Mechanism(s) of cytoprotective and anti-inflammatory activity of PGB1 oligomers: PGBx has potent anti-phospholipase A2 and anti-oxidant activity. Prostaglandins, Leukotrienes and Essential Fatty Acids 43, 63-70 (1991).

Thromboxane A2, as an unstable intermediate between the prostaglandin endoperoxides and thromboxane B2, is a potent inducer of platelet aggregation and causes vasoconstriction.

Ono 1301 is a prostaglandin I2 mimetic coumpound with inhibitory activity against thromboxane A2 synthase. Ono 1301 suppresses pancreatic fibrosis in the DBTC-induced CP model by inhibiting monocyte activity not only with induction of HGF but also by Ono