Prostaglandin Receptor Antagonist

PF-04418948, a chemical probe, is an orally active, potent and selective prostaglandin EP₂ receptor antagonist with an IC₅₀ of 16 nM.

ONO-AE3-208 is a selective and orally active EP4 receptor antagonist with a K_i of 1.3 nM. ONO-AE3-208 shows less potently affects EP3, FP, and TP receptors (K_i of 30 nM, 790 nM, and 2400 nM, respectively). ONO-AE3-208 suppresses cell invasion, migration, and metastasis of prostate cancer.

Palupiprant (E7046) is an orally bioavailable and specific EP4 antagonist, with IC₅₀ of 13.5 nM and K_i of 23.14 nM. Palupiprant exhibits anti-tumor activities.

Grapiprant (CJ-023423) is a selective EP4 receptor antagonist whose physiological ligand is prostaglandin E₂ (PGE₂). Grapiprant displaces [³H]-PGE₂ (1 nM) binding to dog recombinant EP4 receptor with IC₅₀ value of 35 nM and K_i value of 24 nM. Grapiprant has the potential for osteoarthritic pain and inflammation treatment^[3] .

GW627368 (GW627368X) is a novel, potent and selective competitive antagonist of prostanoid EP4 receptor with additional human TP receptor affinity, with pK_i values of 7.0 and 6.8 for human prostanoid EP4 and TP receptors respectively.

Laropiprant is a potent and selective DP receptor antagonist with K_i values of 0.57 nM and 2.95 nM for DP receptor and TP Receptor, respectively.

L-798106 is potent and highly selective prostanoid EP₃ receptor antagonist (K_i=0.3 nM), it also has micromolar activities at the EP₄, EP₁ and EP₂ receptors with K_i values of 916 nM, >5000 nM and >5000 nM, respectively.

RO1138452 is a potent and selective IP (prostacyclin) receptor antagonist. RO1138452 displays high affinity for IP receptors. In human platelets, pK_i is 9.3±0.1; in a recombinant IP receptor system, pK_i is 8.7±0.06.

TG4-155 is a potent, brain-permeant and selective EP2 receptor antagonist with a K_i of 9.9 nM. TG4-155 shows low nanomolar antagonist activity against only EP2 and DP1. TG4-155 has an EP2 Schild K_B of 2.4 nM and displays 550-4750-fold selectivity for EP2 over EP1, EP3, EP4 and IP, but only 14-fold selectivity against the DP1 receptor.

DG-041 is a potent, high affinity and selective EP₃ receptor antagonist with IC₅₀s of 4.6 nM and 8.1 nM in the binding and FLIPR assay, respectively. DG-041 inhibits PGE2 facilitation of platelet aggregation. DG-041 crosses the blood-brain barrier.

Asapiprant is a potent and selective DP₁ receptor antagonist with a K_i of 0.44 nM.

EP4 receptor antagonist 1 is a highly potent and selective competitive prostanoid EP4 receptor antagonist for cancer immunotherapy. EP4 receptor antagonist 1 inhibits human and mouse EP4 receptor with IC₅₀s of 6.1 nM and 16.2 nM, respectively. IC₅₀s >10 μM for human EP1, EP2,and EP3 receptors.

AH 6809 is an antagonist of EP and DP receptor, with K_is of 1217, 1150, 1597, and 1415 nM for the cloned human EP₁, EP₂, EP₃-III, and DP receptor respectively. AH 6809 has a K_i of 350 nM for mouse EP₂ receptor.

Fevipiprant (QAW039, NVP-QAW039) is s an orally active, selective, reversible prostaglandin D2 (DP2) receptor antagonist with an K_d value of 1.14 nM. Fevipiprant has the potential for the research of bronchial asthma.

Timapiprant (OC000459) is a potent, selective, and orally active D prostanoid receptor 2 (DP₂, also known as CRTH2) antagonist. Timapiprant (OC000459) potently displaces [³H] PGD2 from human recombinant DP₂ (K_i=13 nM), rat recombinant DP₂ (K_i=3 nM), and human native DP₂ (K_i=4 nM). Timapiprant (OC000459) inhibits mast cell activation of Th2 lymphocytes and eosinophils.

SC-51322 is a potent and selective antagonist of prostaglandin E2 (PGE₂) receptor (EP ₁), with a pA₂ of 8.1. SC-51322 has the pain-relieving effect.

Seratrodast (AA 2414), an orally active antiasthmatic agent, is a thromboxane A2 receptor (TP) antagonist and ferroptosis inhibitor. Seratrodast reduces lipid ROS production, modulates the systemic xc-/GSH/GPX4 axis, and inhibits JNK phosphorylation and p53 expression. Seratrodast exhibits anti-asthmatic and anti-epileptic activity.

Ramatroban is a selective thromboxane A₂ (TxA₂, IC₅₀=14 nM) antagonist, which also antagonizes CRTH2 (IC₅₀=113 nM) by inhibiting PGD₂ binding.

CJ-42794 (CJ-042794) is a potent, orally active, selective prostaglandin E receptor 4 (EP4) antagonist with an IC₅₀ value of 10 nM, which is 200-fold more selective than EP1, EP2 and EP3. CJ-42794 can be used in research of gastric ulcers.

Vorbipiprant (CR6086) is an orally active EP4 receptor antagonist with high selectivity for the human EP4 receptor (K_i: 16.6 nM). Vorbipiprant has immunomodulatory, anti-inflammatory, antitumor, and anti-angiogenic activities. Vorbipiprant can inhibit the expression of multiple pro-inflammatory cytokines and the activation of immune cells, and convert "cold" tumors unresponsive to immune checkpoint inhibitors into "hot" tumors. Vorbipiprant is used in the research of diseases such as rheumatoid arthritis and colon cancer.