UCB-5307 is a potent TNF signaling inhibitor with a KD of 9 nM for human TNFα. UCB-5307 can penetrate the preformed hTNF/hTNFR1 complex.In Vitro:UCB-5307 inhibits wild-type TNF but does not inhibit L57F TNF. The T1/2 of UCB-5307 is 3.3 h.
UCB-5307 disrupts a preformed hTNF/hTNFR1 complex, can penetrate the preformed complex, dislodging one of the receptors. Preloading hTNF with UCB-5307 blocks one receptor from binding.
UCB-5307 binds to a pocket in the centre of the TNF trimer formed by the movement of the TNF monomers, stabilising the distorted trimer, which leads to reduced signalling through TNFR1.