Lepzacitinib

Lepzacitinib is an inhibitor of JAK1 and JAK3 (IC50s = 1.5 and 3.6 nM, respectively). It selectively inhibits IL-2-induced activation of JAK1/3 over IFN-gamma-induced activation of JAK1/2, GM-CSF-induced activation of JAK2, and IL-12-induced activation of JAK2/tyrosine kinase 2 (TYK2) in isolated human peripheral blood mononuclear cells (PBMCs, IC50s = 19, 97, 794, and 898 nM, respectively). Lepzacitinib is also selective for JAK1 and JAK3 over a panel of 214 additional kinases at 1 µM. Topical application of lepzacitinib (2% solution) inhibits IL-15-induced expression of mRNA encoding chemokine (C-C-motif) ligand 8 (CCL8) by 83% in a porcine model of atopic dermatitis. InChI: InChI=1S/C18H21N5O3/c1-2-26-18(25)14-10-21-17-13(6-8-20-17)16(14)22-12-4-3-9-23(11-12)15(24)5-7-19/h6,8,10,12H,2-5,9,11H2,1H3,(H2,20,21,22)/t12-/m1/s1 InChIKey: QQOPOYMFJLUSBI-GFCCVEGCSA-N SMILES: CCOC(C1=CN=C(NC=C2)C2=C1N[C@H]3CN(CCC3)C(CC#N)=O)=O