AX-024 是一种口服可利用的，首创的TCR-Nck相互作用抑制剂，可选择性地抑制 TCR 触发的 T 细胞活化，IC50值为 1 nM。AX-024 通过靶向SH3结构域调节细胞信号传导。AX-024 具有低毒、高效、高选择性的特点。AX-024 有效抑制白细胞介素-6 (IL-6)，肿瘤坏死因子-α (TNFα)，干扰素-γ (IFN-γ)，IL-10和IL-17A的产生。

AX-024 is an orally available, first-in-class inhibitor of the TCR-Nck interaction that selectively inhibits TCR-triggered T cell activation with an IC 50 ~1 nM. AX-024 modulates cell signaling by targeting SH3 domains. AX-024 has low-acute toxicity and high potency and selectivity, and strongly inhibit the production of IL-6, TNF-α, IFN-γ, IL-10 and IL-17A.

AX-024 is >10,000-fold more potent than the AX-000 hit in terms of inhibition of TCR-triggered T cell proliferation. The IC 50 of AX-024 in this assay is 1 nM, although it shows inhibitory effects at a concentration of 1 pM or less. AX-024 is also a much more potent inhibitor of cytokine release by human peripheral blood mononuclear cells stimulated with anti-CD3 than AX-000, strongly hindering interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-10, and IL-17A production at a concentration of 10 nM. In CD8 + T cells of OT1 TCR transgenic (OT1 Tg ) mice bearing wild-type (WT) AX-024 strongly inhibits T cell proliferation at a concentration of 0.1 nM when OT1 Tg T cells are WT for the PRS mutation. Coimmunoprecipitation experiments in these cells show that Nck recruitment to the TCR is induced upon stimulation in the absence of drug but is inhibited in the presence of AX-024 in a dose-dependent manner at concentrations starting from 1 nM [1].

AX-024-treated group presents less scales and reduces skin thickening compare to the vehicle group. AX-024 significantly reduces thickening of both skin layers, but more effectively of the dermis, which rather resembles that of mice treated with a control cream lacking imiquimod (IMQ). AX-024 significantly diminishes the number of airway inflammatory cells in both assays. Mice receiving AX-024 rapidly recovers from neurological impairment and weight loss, becoming symptom-free by day 30, unlike mice that receives the vehicle, in which ataxia and loss of the righting reflex persist [1].

1370544-73-2

C21H22FNO2

339.4

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years