| CAS |
1370544-73-2 |
| English Name |
AX-024 |
| Synonyms |
AX-024 HCl |
| Molecular Formula |
C21H22FNO2 |
| Molecular Weight |
339.4 |
| Solubility |
Soluble in DMSO |
| Purity |
≥98% |
| Appearance |
Liquid |
| Storage |
Store at 2-8℃，2 years |
| Delivery Time |
1-2 Days |
| MDL |
MFCD30609505 |
| SMILES |
COC1=CC=C(OC2)C(C(C3=CC=C(F)C=C3)=C2CN4CCCC4)=C1 |
| 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 |
| PubChem CID |
56949412 |
| Target Point |
TCR;IFNAR；Interleukin Related |
| Passage |
Immunology & Inflammation |
| Background |
AX-024 specifically inhibits TCR-dependent T cell activation.AX-024 specifically inhibits the earliest TCR signaling events.It has a strong inhibitory effect on the production of IL-6, TNF-α, IFN-γ, IL-10 and IL-17A. |
| Biological Activity |
AX-024 specifically inhibits TCR-dependent T cell activation.AX-024 specifically inhibits the earliest TCR signaling events.AX-024 attenuates the severity of skin inflammation in a psoriasis model as well as of lung inflammation in an asthma model.[1] |
| In Vitro |
Replacing the piperidine substituent by a smaller pyrrolidine ring and adding a methoxy substituent in position 6 gave rise to the lead compound AX-024，which was >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 was 1 nM，although it showed inhibitory effects at a concentration of 1 pM or less. AX-024 was 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 necrosisfactor–a(TNFa)，interferon-g(IFN-g)，IL-10，and IL-17A production at a concentration of 10 nM.[1] |
| 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[1]. |
| Cell Experiment |
Spleen B cells from C57BL/6 mice are labeled with Cell Trace Violet and incubated for 72 hours with either anti-IgM(10 mg/mL)or anti-CD40(5 mg/mL)，supplemented with IL-4(5 ng/mL)or LPS(2.5 mg/mL)in the presence of different concentrations of AX-024. Proliferation is calculated according to the total number of cell divisions[1]. |
| Animal Experiment |
Eight-week-old CD-1 mice are injected intraperitoneally with different amounts of the AX-024 dissolved in 0.5 mL of saline. All animals are observed clinically for the appearance of macroscopically visible adverse reactions twice daily over 14 days，as well as immediately after AX-024 administration. A necropsy is carried out on each animal on day 14，and the abdominal，thoracic，and cranial cavities are examined in situ，together with their associated organs[1]. |
| Data Literature Source |
[1]. Borroto A，et al. First-in-class inhibitor of the T cell receptor for the treatment of autoimmune diseases. Sci Transl Med. 2016 Dec 21;8(370):370ra184 |
| Unit |
Bottle |
| Specification |
5mg 10mg |
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