WHI-P258 is a quinazoline compound that modeling studies suggested would bind to the active site of JAK3 with an estimated Ki value of 72 ?M.1 However, it is inactive at JAK3 (IC50 = >300 ?M) and has been used as a negative control for structurally similar compounds that inhibit platelet aggregation and herpes simplex virus 1 (HSV-1) replication.2,3
1.Sudbeck, E.A., Liu, X.P., Narla, R.K., et al.Structure-based design of specific inhibitors of Janus kinase 3 as apoptosis-inducing antileukemic agentsClin. Cancer Res.5(6)1569-1582(1999) 2.Yakota, S.-i., Yokosawa, N., Okabayashi, T., et al.Induction of suppressor of cytokine signaling-3 by herpes simplex virus type 1 confers efficient viral replicationVirology338(1)173-181(2005) 3.Tibbles, H.E., Vassilev, A., Wendorf, H., et al.Role of a JAK3-dependent biochemical signaling pathway in platelet activation and aggregationJ. Biol. Chem.276(21)17815-17822(2001)