BI-671800 is a highly specific and potent antagonist of chemoattractant receptor-homologous molecule on Th2 cells (DP2/CRTH2), with IC50 values of 4.5 nM and 3.7 nM for PGD2 binding to CRTH2 in hCRTH2 and mCRTH2 transfected cells, respectively[1]. BI-671800 has potential for the treatment of poorly controlled asthma[2].
L 655240 is thromboxane antagonist. L 655240 attenuates early ischemia- and reperfusion-induced arrhythmias in a canine model of coronary artery occlusion. L 655240 also involves in cancer and autoimmune disorders[1].
Dinoprost(Prostaglandin F2α) tromethamine salt is a naturally occurring prostaglandin used in medicine to induce labor and as an abortifacient.
GW627368(GW627368X) is a novel, potent and selective competitive antagonist of prostanoid EP4 receptor(Ki= 100 nM) with additional human TP receptor affinity(Ki= 150 nM).IC50 value: Target: EP4 antagonistin vitro: At recombinant human prostanoid EP4 receptors expressed in HEK293 cells, GW627368X produced parallel rightward shifts of PGE2 concentration-effect (E/[A]) curves resulting in an affinity (pKb) estimate of 7.9 +/- 0.4. GW627368X appears to bind to human prostanoid TP receptors but not the TP receptors of other species. In human washed platelets, GW627368X (10 microM) produced 100% inhibition of U-46619 (EC100)-induced aggregation (approximate pA2 approximately 7.0) [1]. in vivo: Oral administration of GW627368X showed significant tumor regression characterized by tumor reduction and induction of apoptosis. Reduction in prostaglandin E2 synthesis also led to reduced level of VEGF in plasma [2].
GSK345931A is an EP1 receptor antagonist. GSK345931A shows measurable CNS penetration in the mouse and rat and potent analgesic efficacy in acute and sub-chronic models of inflammatory pain[1].
Asapiprant is a potent and selective DP1 receptor antagonist with a Ki of 0.44 nM.
OC000459 is a potent and selective D prostanoid receptor 2 (DP2) antagonist with IC50 of 13 nM.IC50 Value: 13 nM( Ki for hrCRTH2); 3 nM( Ki for Rat rCRTH2);13 nM(Ki for human native CRTH2)Target: D prostanoid receptor 2CRTH2 (chemoattractant receptor expressed on T-helper (Th) type 2 cells) is a G-protein-coupled receptor expressed by Th2 lymphocytes and eosinophils that mediates prostaglandin (PG)D(2)-driven chemotaxis[1]. CRTH2 mediates activation of Th2 cells, eosinophils and basophils in response to prostaglandin D(2). The CRTH2 antagonist OC000459 has been demonstrated to reduce airway inflammation and improve lung function in moderate persistent asthma[2].in vitro: OC000459 is an indole-acetic acid derivative that potently displaces [3H]PGD2from human recombinant DP2 (Ki = 0.013 μM), rat recombinant DP2 (Ki = 0.003 μM), and human native DP2 (Th2 cell membranes; Ki = 0.004 μM) but does not interfere with the ligand binding properties or functional activities of other prostanoid receptors (prostaglandin E1-4 receptors, D prostanoid receptor 1, thromboxane receptor, prostacyclin receptor, and prostaglandin F receptor). OC000459 inhibited chemotaxis (IC50 = 0.028 μM) of human Th2 lymphocytes and cytokine production (IC50 = 0.019 μM) by human Th2 lymphocytes. OC000459 competitively antagonized eosinophil shape change responses induced by PGD2 in both isolated human leukocytes (pKB = 7.9) and human whole blood (pKB = 7.5) but did not inhibit responses to eotaxin, 5-oxo-eicosatetraenoic acid, or complement component C5a. OC000459 also inhibited the activation of Th2 cells and eosinophils in response to supernatants from IgE/anti-IgE-activated human mast cells. OC000459 had no significant inhibitory activity on a battery of 69 receptors and 19 enzymes including cyclooxygenase 1 (COX1) and COX2[3] .in vivo: OC000459 was found to be orally bioavailable in rats and effective in inhibiting blood eosinophilia induced by 13,14-dihydro-15-keto-PGD2 (DK-PGD2) in this species (ED50 = 0.04 mg/kg p.o.) and airway eosinophilia in response to an aerosol of DK-PGD2 in guinea pigs (ED50 = 0.01 mg/kg p.o.) [3].Clinical trial: N/A.
EP3 antagonist 4 (Compound 28) is an EP3 antagonist, with a Ki value of 2 nM for hEP. EP3 antagonist 4 shows low in vivo clearance, high oral AUC, and good bioavailability in the rat full PK studies. EP3 antagonist 4 can be used for research of beta cell dysfunction in diabetes[1].
Bimatoprost is a prostaglandin analog used topically (as eye drops) to control the progression of glaucoma and in the management of ocular hypertension.Target: Prostaglandin ReceptorBimatoprost is a prostaglandin analog/prodrug used topically (as eye drops) to control the progression of glaucoma and in the management of ocular hypertension. It reduces intraocular pressure (IOP) by increasing the outflow of aqueous fluid from the eyes. In December 2008, the indication to lengthen eyelashes was approved by the U.S. Food and Drug Administration (FDA); the cosmetic formulation of bimatoprost is sold as Latisse. In 2008-2011, at least three case series suggested that bimatoprost has the ability to reduce adipose (fat) tissue.Bimatoprost activates prostamide alpha F2 receptors found in the hair follicle to stimulate its growth rate. Research led by Professor Randall and the University of Bradford found that it may also offer a treatment for scalp hair regrowth in trials conducted on samples taken from men undergoing hair transplants. According to Allergan's package labeling, users of its Latisse cosmetic product didn't develop darker irises in clinical studies; however, "patients should be advised about the potential for increased brown iris pigmentation which is likely to be permanent."
ONO-8711 is a potent and selective competitive antagonist of EP1 receptor (Ki = 0.6 and 1.7 nM for human and mouse EP1 respectively). ONO-8711 effectively reduces tumor incidence and multiplicity in mouse models of colon, breast, and oral cancer[1].
CAY10471 Racemate (TM30089 Racemate) is a potent and highly selective prostaglandin D2 receptor CRTH2 antagonist, with a Ki of 0.6 nM for hCRTH2, selective over human thromboxane A2 receptor TP (Ki, >10000 nM) or PGD2 receptor DP (Ki, 1200 nM). CAY10471 Racemate also has effect on mouse and rat orthologs of CRTH2[1].
Prostaglandin E2 is a hormone-like substance that participate in a wide range of body functions such as the contraction and relaxation of smooth muscle, the dilation and constriction of blood vessels, control of blood pressure, and modulation of inflammation.
EP2 receptor antagonist-2 (CID891729) is an antagonist of EP2 receptor. EP2 receptor antagonist-2 inhibits the EP2 receptor activation induced by PGE2. EP2 receptor antagonist-2 also suppresses lactate dehydrogenase (LDH) release induced by N-methyl-D-aspartate (NMDA)[1].
KW-8232, an orally active anti-osteoporotic agent, and can reduces the biosynthesis of PGE2[1].
Nedocromil sodium suppresses the action or formation of multiple mediators, including histamine, leukotriene C4 (LTC4), and prostaglandin D2 (PGD2).
Ro 22-9194 inhibits aggregation and thromboxane Az (TXA2) synthetase activity in rabbit and human platelets. Ro 22-9194 has a potent inhibitory action against various types of model arrhythmias. Ro 22-9194 has non-cholinergic cardiac depressant properties with its vasodilating action[1][2].
Saikogenin D is isolated from Bupleurum chinense, has anti-inflammatory effects. Saikogenin D activates epoxygenases that converts arachidonic acid to epoxyeicosanoids and dihydroxyeicosatrienoic acids, and the metabolites secondarily inhibit prostaglandin E2 (PGE2) production. Saikogenin D results in an elevation of [Ca2+]i due to Ca2+ release from intracellular stores[1][2].
Treprostinil palmitil (TP) is the prodrug of DP1 and EP2 agonist, Treprostinil (UT-15), whose EC50 values were 0.6 and 6.2 nM, respectively. Treprostinil palmitil is a pure prodrug and possesses no inherent binding to G-protein coupled receptors including prostanoid receptors[1][2].
11-Deoxy Prostaglandin E2 is a selective agonist of EP4 with an EC50 of 0.66 nM. 11-Deoxy Prostaglandin E2 is an analog of prostaglandin E2. 11-Deoxy Prostaglandin E2 can be used in study bone healing, heart failure, and other receptor associated conditions[1][2].
MRE-269 is an active metabolite of selexipag, and acts as a selective IP receptor agonist.
U66858 is a potent inhibitor of LTB4 production in human whole blood. U66858 also exhibits significant inhibition of lipoxygenase and TXB2 release.
RO1138452 is a potent and selective IP (prostacyclin) receptor antagonist. RO1138452 displays high affinity for IP receptors. In human platelets, pKi is 9.3±0.1; in a recombinant IP receptor system, pKi is 8.7±0.06.
Selexipag (NS-304) is an orally available and potent agonist for the Prostacyclin (PGI2) receptor (IP receptor).
Agnuside is a compound isolated from Vitex negundo, down-regulates pro-inflammatory mediators PGE2 and LTB4, and reduces the expression of cytokines, with anti-arthritic activity[1].
AS604872 is an orally active, potent and selective prostaglandin F2α receptor (FP) antagonist with a Ki of 35 nM in humans, 158 nM in rats and 323 nM in mice. AS604872 inhibits contractions and delays labour[1].
Nedocromil suppresses the action or formation of multiple mediators, including histamine, leukotriene C4 (LTC4), and prostaglandin D2 (PGD2).
Treprostinil sodium is a potent DP1 and EP2 agonist with EC50 values of 0.6±0.1 and 6.2±1.2 nM, respectively.
L-902688 is a potent, selective and orally active EP4 receptor agonist with a Ki of 0.38 nM and an EC50 of 0.6 nM. L-902688 shows >4,000-fold selective for EP4 over other EP and prostanoid receptors[1][2].
Carboprost tromethamine is the synthetic 15-methyl analogue of prostaglandin F2α. Carboprost tromethamine can effectively promote law contraction of the uterus and significantly reduce the amount of bleeding during and after delivery[1][2].
AL-3138 (11-Deoxy-16-fluoro PGF2α) is a prostaglandin F2 alpha (PGF2alpha) analogue that antagonises FP prostaglandin receptor-mediated inositol phosphate production[1].