An EP4 receptor antagonist
MF766 is an antagonist of the prostaglandin E2 (PGE2) receptor subtype EP4 (Ki = 0.23 nM).1 It is selective for EP4 over the PGD2 receptor subtype DP1 (Ki = 1,648 nM) as well as the EP1, EP2, EP3, and CRTH2/DP2 receptors, the PGI2 receptor (IP), thromboxane receptor (TP), and PGF receptor (FP; Kis = >6,000 nM for all). It inhibits cAMP accumulation induced by PGE2 in HEK293 cells (IC50 = 1.3 nM). MF766 (312.5 and 1,250 nM) reverses PGE2-induced decreases in IFN-γ production in IL-2-stimulated primary human natural killer cells.2 It reduces paw edema in a rat model of adjuvant-induced arthritis in a dose-dependent manner.1 MF766 (30 mg/kg) inhibits tumor growth in a CT26 murine colon cancer model.2
1.Colucci, J., Boyd, M., Berthelette, C., et al.Discovery of 4-{1-[({1-[4-(trifluoromethyl)benzyl]-1H-indol-7-yl}carbonyl)amino]cyclopropyl}benzoic acid (MF-766), a highly potent and selective EP4 antagonist for treating inflammatory painBioorg. Med. Chem. Lett.20(12)3760-3763(2010) 2.Wang, Y., Cui, L., Georgiev, P., et al.Combination of EP4 antagonist MF-766 and anti-PD-1 promotes anti-tumor efficacy by modulating both lymphocytes and myeloid cellsOncoimmunology10(1)1896643(2021)
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