| Chemical Properties | Back Directory | [density ]
1.32±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS (pH 7.2) (1:6): 0.14 mg/ml | [form ]
A crystalline solid | [pka]
4.19±0.10(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
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[1]. | [Biological Activity]
EP4 receptor antagonist 1 is an antagonist of the prostaglandin E2 (PGE2) receptor EP4 that has an IC50 value of 6.1 nM in a calcium flux assay using CHO cells co-expressing the human receptor and Gα16.1 It is selective for EP4 over EP1, EP2, and EP3 receptors (IC50s = >10,000 nM for all). EP4 receptor antagonist 1 inhibits PGE2-induced β-arrestin recruitment in HEK293 cells expressing EP4. It reverses ERK phosphorylation induced by PGE2 in CHO cells expressing EP4 and decreases GM-CSF-induced expression of Il1b, Il4ra, Il6, Arg1, Cox2, and Il10 in RAW 264.7 cells when used at a concentration of 10 μM. EP4 receptor antagonist 1 (50 and 150 mg/kg once per day) reduces tumor volume and increases infiltration of CD8+ T cells into tumors in a murine colon carcinoma model. | [in vivo]
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 1 is well tolerated in mice at the tested dosage[1].
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) of 4.7 h[1]. | Animal Model: | BALB/c female mice (6-week-old)bearing CT26 colon cancer model[1] | | 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[1] | | 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) of 4.1 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) of 4.7 h at a dose of 5 mg/kg (orally). |
| [References]
1.Yang, J.-J., Yu, W.-W., Hu, L.-L., et al.Discovery and characterization of 1 H-1,2,3-triazole derivatives as novel prostanoid EP4 receptor antagonists for cancer immunotherapyJ. Med. Chem.63(2)569-590(2020)
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ChemeGen 中國
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https://www.chemegen.com |
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