ZK 216348

ZK 216348 ((+)-ZK 216348) is a nonsteroidal selective glucocorticoid receptor agonist with an IC₅₀ of 20.3 nM. ZK 216348 also binds to Progesterone and mineralocorticoid receptors with IC₅₀s of 20.4 nM and 79.9 nM, respectively. ZK 216348 has antiinflammatory activity similar to Prednisolone and induces less transactivation-mediated side effects^[1][2]. IC50 & Target:IC50: 20.3 nM (Glucocorticoid recepto), 20.4 nM (Progesterone receptor ) and 79.9 nM (mineralocorticoid receptor)^[1] In Vitro: In human peripheral blood mononuclear cells (PBMCs), ZK 216348 inhibits TNF-α and IL-12 with IC₅₀ of 89 nM and 52 nM, respectively^[1].
Participation of an active GR in the antiinflammatory response of ZK 216348 is further investigated in Caco-2 cells, where the TNF-α-induced expression of the proinflammatory cytokine IL-8 is suppressed in the presence of ZK 216348^[2]. In Vivo: ZK 216348 (1-30? mg/kg; subcutaneous injection; for 24 hours; NMRI mice and Wistar rats) treatment inhibits ear edema in both mice and rats. A markedly superior side-effect profile is found in ZK 216348 with regard to increases in blood glucose, spleen involution, and, to a lesser extent, skin atrophy^[1].