Tumor necrosis factor (TNF, also referred to as TNFα) is a pro-inflammatory cytokine belonging to a family of trimeric proteins. TNF exerts its biological functions through activating distinct signaling pathways such as nuclear factor κB (NF-κB) and c-Jun N-terminal kinase (JNK). Thus, TNF plays an important role in diverse cellular events such as cell survival, proliferation, differentiation, and death. TNF can suppress tumor cell proliferation and induce tumor regression. Meanwhile, it is a key mediator in autoimmune diseases such as rheumatoid arthritis and Crohn’s disease. Since the TNF gene was cloned in 1984, extensive research has revealed a variety of roles for TNF under physiological conditions such as in body development and immunity, and in pathological responses such as inflammation, tumor growth, transplant rejection, rheumatoid arthritis, and septic shock.

In regard to cancer, TNF is a double-dealer. On the one hand, TNF could be a cancer killer. Its anticancer property is mainly through inducing cancer cell death, a process that could be used for cancer research. On the other hand, TNF could be an endogenous tumor promoter. TNF stimulates proliferation, survival, migration, and angiogenesis in cancer cells, resulting in tumor promotion. Thus, TNF is a double-edged sword that could be either pro- or anti-tumorigenic.

UCB-5307 is a TNF signaling inhibitor.

TNF antagonist treatments have been one of the success stories of recent years. Biologics such as infliximab, etanercept, adalimumab, golimumab, and certolizumab pegol have proved efficacious in the clinic. UCB-5307 is a potent TNF inhibitor that can compromise signaling and inhibit the functions of TNF in vitro and in vivo. Preloading hTNF with UCB-5307 blocked one receptor from binding. Additionally, UCB-5307 targets TNF directly and inhibits activity by destabilizing the TNF trimer, resulting in a dimer that is no longer able to interact with the receptor.

All in all, UCB-5307 is a TNF signaling inhibitor with a KD of 9 nM. UCB-5307 can penetrate the preformed hTNF/hTNFR1 complex.


Holbrook J, et, al. F1000Res. 2019 Jan 28;8:F1000 Faculty Rev-111.