AX-024

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 IC50 ~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.

Product information

CAS Number: 1370544-73-2

Molecular Weight: 339.40

Formula: C21H22FNO2

Chemical Name: 1-{[4-(4-fluorophenyl)-6-methoxy-2H-chromen-3-yl]methyl}pyrrolidine

Smiles: COC1C=C2C(=CC=1)OCC(CN1CCCC1)=C2C1C=CC(F)=CC=1

InChiKey: VMMKGVRPILDZML-UHFFFAOYSA-N

InChi: InChI=1S/C21H22FNO2/c1-24-18-8-9-20-19(12-18)21(15-4-6-17(22)7-5-15)16(14-25-20)13-23-10-2-3-11-23/h4-9,12H,2-3,10-11,13-14H2,1H3

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 35 mg/mL (103.12 mM; Need ultrasonic and warming).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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.

Products are for research use only. Not for human use.