EP4 receptor antagonist 1

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

EP4受体拮抗剂1抑制人和小鼠EP4受体，IC50分别为6.1 nM和16.2 nM。

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.EP4 receptor antagonist 1 is a highly potent and selective competitive prostanoid EP4 receptor antagonist for cancer immunotherapy.(In Vitro):EP4 receptor antagonist 1 inhibits the activity of the CRE reporter in HEK293 cells with an IC50 of 5.2±0.4 nM in a dose-dependent manner. EP4 receptor antagonist 1 dose-dependently inhibits PGE2-stimulated β-arrestin recruitment in HEK293-EP4 cells with an IC50 of 0.4±0.1 nM. EP4 receptor antagonist 1 inhibits PGE2-stimulated cAMP accumulation in HEK293-EP4 cells with an IC50 of 18.7±0.6 nM in a dose-dependent manner. EP4 receptor antagonist 1 (1 nM-10 μM) reverses PGE2-induced ERK phosphorylation in a concentration-dependent manner. The IC50s are >10 μM for human EP1, EP2, and EP3 receptors.(In Vivo):EP4 receptor antagonist 1 (1 mg/kg; i.v.) demonstrates moderate clearance of 1.7 L/h/kg in mice with a corresponding favorable half-life of 4.1 h. EP4 receptor antagonist 1 (5 mg/kg; orally) exhibits good bioavailability of 48.0% in mice with a corresponding favorable half-life of 4.7 h. EP4 receptor antagonist 1 (16, 50, and 150 mg/kg; oral) causes significant inhibition of tumor growth in BALB/c female mice. No significant body weight loss is found in any mouse cohorts. EP4 receptor antagonist 1 is well tolerated in mice at the tested dosage.

The antagonistic effect of EP4 receptor antagonist 1 (Compounds 59) on human EP4 in calcium flux assay with an IC50 of 6.1±0.2 nM in CHO-Gα16 cells overexpressing human EP4 receptor. The antagonistic effect of EP4 receptor antagonist 1 on human EP4 in calcium flux assay with an IC50 of 16.2±1.7 nM in CHO-Gα16 cells overexpressing mouse EP4 receptor.EP4 receptor antagonist 1 dose dependently inhibits PGE2-stimulated cAMP accumulation in HEK293-EP4 cells with an IC50 of 18.7±0.6 nM. EP4 receptor antagonist 1 dose-dependently inhibits the activity of the CRE reporter in HEK293 cells with an IC50 of 5.2±0.4 nM.EP4 receptor antagonist 1 dose-dependently inhibits PGE2-stimulated β-arrestin recruitment in HEK293-EP4 cells with an IC50 of 0.4±0.1 nM.EP4 receptor antagonist 1 (1 nM-10 μM) reverses PGE2-induced ERK phosphorylation in a concentration-dependent manner. Western Blot Analysis Cell Line:CHO-EP4 cells Concentration:1 nM, 100 nM, 10 μM Incubation Time:Pretreated for 20 min and then subjected to 30 nM PGE2 simulation for 10 min.Result:Reversed PGE2-induced ERK phosphorylation in a concentration-dependent manner.

EP4 receptor antagonist 1 (16, 50, and 150 mg/kg; orally; once daily for two weeks) causes significant inhibition of tumor growth in BALB/c female mice. No significant body weight loss is found in any mouse cohorts. EP4 receptor antagonist 1is well tolerated in mice at the tested dosage.EP4 receptor antagonist 1 (1 mg/kg; intravenously) demonstrates moderate clearance (CL=1.7 L/h/kg) in mice with a corresponding favorable half-life (t1/2) of 4.1 h.EP4 receptor antagonist 1 (5 mg/kg; orally) exhibits good bioavailability (F=48.0%) in mice with a corresponding favorable half-life (t1/2) of4.7 h. Animal Model:BALB/c female mice (6-week-old)bearing CT26 colon cancer model Dosage:16, 50, and 150 mg/kg Administration:Orally; once daily for two weeks Result:Tumor growth inhibition (TGI) was 24.6% at 16 mg/ kg, 54.7% at 50 mg/kg, and 63.8% at 150 mg/kg. Animal Model:BALB/c female mice Dosage:1 mg/kg and 5 mg/kg (Pharmacokinetic Analysis) Administration:Intravenously or orally at a dose of 1 mg/kg (5 mL/kg) and 5 mg/kg (10 mL/kg),respectively.Result:Demonstrated moderate clearance ( CL=1.7 L/h/kg) in mice with a corresponding favorable half-life (t1/2) of4.1 h at a dose of 1 mg/kg (intravenously). Exhibited good bioavailability (F=48.0%) in mice with a corresponding favorable half-life (t1/2) of4.7 h at a dose of 5 mg/kg (orally).

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GPCR/G Protein

Prostaglandin Receptor

HIV-1| IFN-γ| IKK| IL Receptor| JAK| NADPH-oxidase| NF-κB| NO| ROS| STAT| TLR| TNF-α

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2287259-07-6

458.441

C23H21F3N4O3

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (218.14 mM)

C\C=C\c1nnn(Cc2ccc(cc2)C(F)(F)F)c1C(=O)N[C@@H](C)c1ccc(cc1)C(O)=O

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(-20℃)

With Ice Pack

≥ 2 years