AS2863619

2241300-51-4

405.24

DMSO : 250 mg/mL (616.92 mM; Need ultrasonic)

Cell Cycle/DNA Damage; JAK/STAT Signaling; Stem Cell/Wnt

AS2863619 enables conversion of antigen-specific effector/memory T cells into Foxp3⁺ regulatory T (T_reg) cells for the treatment of various immunological diseases. AS2863619 is a potent, orally active cyclin-dependent kinase 8 (CDK8) and CDK19 inhibitor with IC₅₀s of 0.61 nM and 4.28 nM, respectively. STAT5 activation enhanced by AS2863619 inhibition of CDK8/19, which consequently activates the Foxp3 gene^[1]. In Vitro: AS2863619 (1 uM; 22 hours; mouse CD4⁺ T cells) treatment suppresses serine phosphorylation of the PSP motif of STAT5b to ca.40% while enhancing tyrosine phosphorylation in the C-terminal domain to ca.160% of control-treated samples^[1]. In Vivo: AS2863619 (30 mg/kg; oral administration; daily; for 2 weeks; mice) treatment after sensitization with 2, 4-dinitrofluorobenzene (DNFB) dampens the degree of the secondary response, with milder infiltration of inflammatory cells into the skin and decreases ratios of interferon-gamma⁺ (IFN-gamma⁺) cells in a skin contact hypersensitivity model, when compared with vehicle-treated control mice. T_reg depletion before the elicitation of the secondary response abolishes AS2863619-induced suppression. KLRG1⁺ Foxp3⁺ T cells are specifically increased in DNFB sensitized AS2863619-treated mice^[1].