KF-0210

KF-0210 is a small molecule oral drug developed by Keythera Biopharmaceuticals. It is a highly selective and potent antagonist of E-type prostaglandin receptor 4 (EP4), with a selectivity of 500 folds more potent than other prostaglandin receptors. Prostaglandin E2 (PGE2) is one of the main products produced by the action of cyclooxygenase (COX) from arachidonic acid. It is well known to be involved in many physiological and pathophysiological reactions. For example, it is elevated in some cancer tissues and involved in the inhibition of antitumor immune activity in tumor microenvironment, and thus contributes to the tumor growth and metastasis. EP4 receptor is a major PGE2 recepor in tumor tissues. Inhibition of EP4 receptor can block PGE2 function, increase antitumor immune responses and thus reduce tumor growth and metastasis. When combined with anti PD-(L)1 antibody, EP4 antagonist may also increase the response to the therapy. Therefore, EP4 antagonist become a potential novel therapy for cancers, especially when combined with PD-(L)1 antibodies. PGE2 is also known to be involved in the inflammation and pain in osteoarthritis through EP4 receptor. Selective EP4 antagonist can also achieve anti-inflammatory and analgesic effects by blocking the downstream signal pathway of PGE2, without affecting the levels of prostaglandins, especially PGI2, which can avoid the adverse reactions in the kidneys and cardiovascular systems caused by COX2 inhibitors.