AX-024 (1704801-24-0) is a potent (IC50 ~ 1 nM) and specific inhibitor of T cell antigen receptor (TCR)-dependent T cell activation. It inhibited neither B cell proliferation triggered by B cell antigen receptor (BCR), TLR4, CD40 agonists nor IL-2-dependent proliferation of T lymphoblasts. AX-024 binds to the SH3.1 domain of the adaptor protein Nck blocking its interaction with the CD3e subunit on the T cell antigen receptor. AX-024 displayed protective effects in mouse models of psoriasis, allergic asthma, and multiple sclerosis. Importantly, the therapeutic effect of AX-024 persisted after removal of the drug in contrast to fingolimod suggesting a persistent modification of autoimmune T cells. Currently in clinical trials.
1) Borroto et al. (2016), First-in-class inhibitor of the T cell receptor for the treatment of autoimmune diseases; Sci. Transl. Med., 8 370ra184