Use of EP4 receptor antagonists for the treatment of NASH-associated liver cancer
This invention is directed to prostaglandin E2 receptor 4 (EP4) antagonists useful in the treatment of nonalcoholic steatohepatitis (NASH)-associated liver cancer in a human or animal. The method comprises administering one or more of Compound A, Compound B or Compound C, or pharmaceutically acceptable salts thereof, as the EP4 antagonist(s). The method may include a pharmaceutical composition comprising the EP4 antagonist, and may include one or more other active agents and/or therapies.
1. A method for the treatment of NASH-associated liver cancer, which comprises administering a pharmaceutically effective amount of 3-[2-(4-{2-ethyl-4,6-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl}phenyl)ethyl]-1-[(4-methylbenzene)sulfonyl]urea or a pharmaceutically acceptable salt thereof to a human or an animal in need thereof.
2. The method of claim 1 , further comprising administering the pharmaceutically effective amount of 3-[2-(4-{2-ethyl-4,6-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl}phenyl)ethyl]-1-[(4-methylbenzene)sulfonyl]urea or salt thereof in combination with a second active agent, an anti-tumor therapy or both.
3. The method of claim 2 , wherein the second active agent is an immune checkpoint inhibitor.
4. The method of claim 2 , wherein the second active agent is a PD-1 inhibitor.
5. A method of therapy for the treatment of NASH-associated liver cancer in a human or an animal in need thereof, which results in at least one effect selected from the group consisting of:
increasing DCs, mouse CD103 + DC or a corresponding DC class in the human or the animal, which activates anti-tumor immune function in the human or the animal,
decreasing Foxp3 + Treg cells which suppress anti-tumor immune function in the human or the animal,
increasing CD8 + /Treg population ratio in the human or the animal,
increasing population of activated CD8 + T cells in the human or the animal, and
decreasing PD-1 expression in CD8 + T cells in the human or the animal,
wherein the method comprises administering a therapeutically effective amount of 3-[2-(4-{2-ethyl-4,6-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl}phenyl)ethyl]-1-[(4-methylbenzene)sulfonyl]urea or a pharmaceutically acceptable salt thereof to the human or the animal.
6. The method of claim 5 , further comprising administering the pharmaceutically effective amount of 3-[2-(4-{2-ethyl-4,6-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl}phenyl)ethyl]-1-[(4-methylbenzene)sulfonyl]urea or salt thereof in combination with a second active agent, an anti-tumor therapy or both.
7. The method of claim 6 , wherein the second active agent is an immune checkpoint inhibitor.
8. The method of claim 6 , wherein the second active agent is a PD-1 inhibitor.