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In vitro: E7046 reverses the immunosuppressive effects of PGE2 on activation and differentiation of human myeloid cells through selective EP4 antagonism.
In vivo: In the CT-26 tumor model, the E7046/RT combination causes the anti-tumor memory response of 9 animals. In the 4T1 model, the combination of E7046 and RT also produces significant better tumor growth inhibition activity compared with each treatment alone. The combination significantly improves survival by inhibiting the subsequent spontaneous lung metastasis of 4T1 tumors. E7046 (150 mg/kg) inhibits the growth of multiple syngeneic tumor models. Blockade of EP4 signaling promotes anti-tumor DC differentiation and slows tumor growth in mice. E7046 treatment reduces the growth or even rejected established tumors in vivo in a manner dependent on both myeloid and CD8C T cells. Furthermore, co-administration of E7046 and E7777, an IL-2-diphtheria toxin fusion protein that preferentially kills Tregs, synergistically disrupts the myeloid and Treg immunosuppressive networks, resulting in effective and durable anti-tumor immune responses in mouse tumor models.
| Cell Experiment | |
|---|---|
| Cell lines | BM cells |
| Preparation method | For certain experiments, CT26, 4T1 cell supernatants, and/or EP1 (SC-57089), EP2 (ER-880696), EP3 (L-798106), or EP4 (E7046) antagonists at 1 mM, are added to the BM cells. To assess the effect of differentiated BM cells on T cell proliferation, mouse BM cells differentiated are co-cultured for 72 hours with anti-CD3/CD28 Dynabeadsstimulated and CFSE (1 mM)-stained T cells. |
| Concentrations | 1 mM |
| Incubation time | 72 h |
| Animal Experiment | |
|---|---|
| Animal models | Female BALB/c mice |
| Formulation | 0.5% methylcellulose |
| Dosages | 100 or 150 mg/kg |
| Administration | p.o. |
| Molecular Weight | 483.39 |
| Formula | C22H18F5N3O4 |
| CAS Number | 1369489-71-3 |
| Solubility (25°C) | DMSO: ≥ 35 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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