Targeting the adenosine A2A receptor, a critical mediator of immunosuppression on the tumor microenvironment, has emerged as a strategy to improve cancer immunotherapy, and several A2A receptor antagonists are under clinical evaluation both as monotherapy and in combination with checkpoint inhibitors.

Tumor necrosis factor-α (TNF-α) is a cytokine involved in the regulation of inflammation in several autoimmune and inflammatory disorders such as rheumatoid arthritis, ulcerative colitis, or psoriasis. Anti-TNF biological treatments in place are effective but there is a need for alternatives with novel pharmacological profiles to overcome their limitations.

Interleukin-4 (IL-4) plays an important role in regulating inflammation. While several antibody-based options targeting IL-4 have been reported, strategies based on small molecule inhibitors have proven difficult to find.