Prostaglandin Receptor Antagonist

HTL0039732 is an orally active antagonist of the prostaglandin EP4 receptor (Prostaglandin E2 Receptor EP4). HTL0039732 reverses PGE₂-induced differentiation toward M2-like macrophages. HTL0039732 exhibits efficacy in syngeneic tumor models and acts synergistically with PD-1/PD-L1 pathway blockers. HTL0039732 can be used for the research of advanced solid tumors.

TP-18 is a potent and orally active dual EP2/EP4 antagonist with IC₅₀ values of 9.5 nM (EP2) and 3.3 nM (EP4). TP-18 effectively depletes a highly immunosuppressive VSIG4high tumor-associated macrophage (TAM) subset and enhances cytotoxic CD8+ T cell-mediated colorectal cancer (CRC) tumor elimination. TP-18 dampens the expression of VSIG4 by blunting EP2/EP4-Gαs-PKA signaling. TP-18 enhances the sensitivity of anti-PD-1 therapy in CRC mouse models and in patient-derived tumor immune organoids. TP-18 can be used to study colorectal cancer.

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.