Description
AX-024 is an inhibitor of the TCR-Nck interaction that selectively inhibits TCR-triggered T cell activation. AX-024 modulates cell signaling by targeting SH3 domains and has low-acute toxicity and high potency and selectivity in the inhibition of the production of IL-6, TNF-α, IFN-γ, IL-10 and IL-17A.
Uses
AX-024, is >10,000-fold more potent than the AX-000 hit in terms of inhibition of TCR-triggered T cell proliferation. It is a cytokine release inhibitor which can strongly inhibit the production of interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), interferon-γ (IFN-γ), IL-10 and IL-17A.
in vitro
AX-024 reduces T cell proliferation upon weak T cell receptor (TCR) stimulation but neither significantly affects phosphorylation of Zap70 (ζ chain of T cell receptor–associated protein kinase 70) nor interacts directly with Nck1-SH3. AX-024 is likely not involved in modulating the Nck/TCR interaction but probably has other targets in T cells. An array of biophysical techniques did not detect a direct interaction between AX-024 and Nck-SH3.1 in vitro._x000D_
_x000D_
Reference: J Biol Chem. 2020 Jun 5;295(23):7849-7864. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278359/#B11
target
AX-024 is an inhibitor of the TCR-Nck interaction that selectively inhibits TCR-triggered T cell activation with an IC50 ~1 nM.
