Palupiprant

Palupiprant (E7046) is an orally bioavailable and specific EP4 antagonist, with IC₅₀ of 13.5 nM and K_i of 23.14 nM. Palupiprant exhibits anti-tumor activities^[1][2]. IC50 & Target:IC50: 13.5 nM (EP4)^[2]
Ki: 23.14 nM (EP4)^[2] In Vitro:Palupiprant (E7046) reverses the immunosuppressive effects of PGE2 on activation and differentiation of human myeloid cells through selective EP4 antagonism^[2]. In Vivo:In the CT-26 tumor model, the Palupiprant/RT combination causes the anti-tumor memory response of 9 animals. In the 4T1 model, the combination of Palupiprant 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^[1]. Palupiprant (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. Palupiprant 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 Palupiprant 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^[2].