Catalog No.: PC-24914Not For Human Use, Lab Use Only.
AS2863619 is a potent, selective and orally active inhibitor of CDK8 and CDK19 with IC50 of 0.61 nM and 4.28 nM, respectively, AS2863619 is a potent Foxp3 inducer in Tconv cells with EC50 of 32.5 nM.
AS2863619 is a potent, selective and orally active inhibitor of CDK8 and CDK19 with IC50 of 0.61 nM and 4.28 nM, respectively, AS2863619 is a potent Foxp3 inducer in Tconv cells with EC50 of 32.5 nM. AS2863619 could generate Foxp3+ T cells from naïve Foxp3−CD4+ Tconv cells in a dose-dependent fashion, also substantially enhances FOXP3 expression in human CD4+ and CD8+ Tconv cells in the peripheral blood. AS2863619 does not exhibit cellular toxicity or hinder proliferative activity of Tconv cells in the concentration range having Foxp3-inducing activity. AS2863619 inhibits the ability of activated CDK8/19 to phosphorylate the serine residue in the PSP motif of STAT5, augments the retention of the tyrosine-phosphorylated STAT5 in the nucleus, leading to enhanced activation of STAT5, which consequently activates the Foxp3 gene. AS2863619 (30 mg/kg) induced Foxp3 in KJ1-26+ T cells in DO11.10 TCR transgenic mice, effectively suppressed skin contact hypersensitivity and autoimmune disease in animal models.
