EP 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.

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.

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.

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.

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.

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.

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.

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.

MF498 is a selective and orally active E prostanoid Receptor 4 (EP4) antagonist with a K_i value of 0.7 nM. MF498 can be used in the research of inflammation, such as rheumatoid and osteoarthritis.

MF-766 is a highly potent, selective and orally active EP4 antagonist with a K_i of 0.23 nM. MF-766 behaves as a full antagonist with an IC₅₀ of 1.4 nM (shifted to 1.8 nM in the presence of 10% HS) in the functional assay. MF-766 can be used for cancer and inflammation diseases research.

SC 51089 free base is a selective antagonist of prostaglandin E₂ EP1 receptor, with K_is of 1.3, 11.2, 17.5, and 61.1 μM for EP1, TP, EP3, and FP receptors, respectively. SC 51089 free base exhibits neuroprotective activity.

EP3 antagonist 3 (compound 2) is an orally active, potent and selective EP3 antagonist, with a pK_i of 8.3. EP3 antagonist 3 shows excellent pharmacokinetic properties. EP3 antagonist 3 can be used for overactive bladder (OAB) research.

L-826266 is a selective and competitive EP3 receptor antagonist. L-826266 can be used for convulsive disorders research.

EP2 receptor antagonist-1 (compound 1) is a potent, reversible, and agonist dependent allosteric prostaglandin EP2 receptor antagonist. EP2 receptor antagonist-1 shows anti-inflammatory effects.

AAT-008 is a potent, selective, and orally active prostaglandin EP4 receptor antagonist with K_is of 0.97 and 6.1 nM for recombinant human EP4 and recombinant rat EP4, respectively. AAT-008 exerts tumor growth delay in mice bearing CT26WT colon tumors when combined with radiotherapy. AAT-008 can be used for the study of acute and chronic inflammatory pain and cancer .