JAK3-IN-1 is a potent JAK3 inhibitor with IC50 of 4.8 nM, also inhibits JAK1 (IC50 = 896 nM) and JAK2 (IC50 = 1050 nM).
JAK3-IN-1 provides a set of useful tools to pharmacologically interrogate JAK3-dependent biology. JAK3-IN-1 completely inhibits IL-4 induced p-STAT6 at a concentration of 500 nM and only partially inhibits IFN-induced p-STAT1 at a concentration of 5.0 M. In a similar way, JAK3-IN-1 exhibits consistent potency and selectivity for JAK3 in leukemia cancer cell lines: TALL-1 and OCL-AML5.
JAK3-IN-1 demonstrates reasonable pharmacokinetic properties, with moderate T1/2 of 1.4 h, area under the curve (AUC) value of 795 ngh/mL following a 10 mg/kg oral dose and good oral
bioavailability of 66%.