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AX-024
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AX-024
CAS No. : 1370544-73-2
MCE 站:AX-024
产品活性: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。
研究领域:Apoptosis | Immunology/Inflammation
作用靶点:TNF Receptor | Interleukin Related | IFNAR
In Vitro: AX-024 is >10,000-fold more potent than the AX-000 hit in terms of inhibition of TCR-triggered T cell proliferation. The IC50 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 (OT1Tg) mice bearing wild-type (WT) AX-024 strongly inhibits T cell proliferation at a concentration of 0.1 nM when OT1Tg 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.
In Vivo: 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.
相关产品:Clinical Compound Library Plus | Bioactive Compound Library Plus | Apoptosis Compound Library | Immunology/Inflammation Compound Library | Kinase Inhibitor Library | Clinical Compound Library | Differentiation Inducing Compound Library | Pyroptosis Compound Library | Orally Active Compound Library | Resatorvid | CCCP | Disulfiram | Vadimezan | Shikonin | Tocilizumab | Fisetin | N-Formyl-Met-Leu-Phe | Adalimumab | R-7050 | QNZ | IFN alpha-IFNAR-IN-1 hydrochloride | Infliximab | Diacerein | Cridanimod | Vidofludimus | LMT-28 | Muscone | SC144 | Hydrocortisone hemisuccinate | RCGD423 | SPD304 | Etanercept | Forsythoside B | Apratastat | Neochlorogenic acid | Y-320 | Ginsenoside Rh1 | Astilbin | Semapimod tetrahydrochloride
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