GDC-046 is a tyrosine kinase 2 (TYK2) inhibitor (Ki = 4.8 nM).1 It is selective for TYK2 over JAK1, -2, and -3 (Kis = 83.8, 27.6, and 253 nM, respectively). GDC-046 selectively inhibits TYK2-mediated IL-12-induced phosphorylation of STAT4 over JAK1-mediated IL-6-induced phosphorylation of STAT3 and JAK2-mediated erythropoietin-induced phosphorylation of STAT5 in cell-based assays (EC50s = 380, 2,000, and 1,700 nM, respectively).
1.Liang, J., van Abbema, A., Balazs, M., et al.Lead optimization of a 4-aminopyridine benzamide scaffold to identify potent, selective, and orally bioavailable TYK2 inhibitorsJ. Med. Chem.56(11)4521-4536(2013)