Ixekizumab

Ixekizumab (LY2439821) is a humanized IgG4 monoclonal antibody that selectively binds and neutralizes interleukin IL-17A (K_D<3 pM). Ixekizumab directly blocks IL-17A binding to IL-17RA (IL-17A receptor) but does not bind to other IL-17 family members. Ixekizumab is used for the research of moderate-to-severe plaque psoriasis^[1][2]. In Vitro: The equilibrium K_D of Ixekizumab for human and cynomolgus monkey IL-17A were 1.8 pM and 0.8 pM, respectively. Ixekizumab also bound to rabbit IL-17A, but the affinity was lower, and the binding was heterogeneous (K_D of 1.3 nM and 14 nM). Ixekizumab shows no binding to either mouse or rat IL-17A^[1].
Ixekizumab (0.1-10000 pM) inhibits human IL-17A- or human IL-17A/F heterodimer-induced growth-regulated oncogene (GRO)α secretion from HT-29 cells in a dose-dependent fashion. Ixekizumab inhibits cynomolgus monkey IL-17A-induced GROα secretion from HT-29 cells in a dose-dependent fashion^[1]. In Vivo: Ixekizumab (0.001-1 mg/kg; i.v.) is able to decrease human IL-17A-induced keratinocyte chemoattractant (KC) secretion in the plasma of the C57BL/6 mice in a dose-dependent manner^[1].
In male cynomolgus monkeys, following IV administration of 1 mg/kg, Ixekizumab is eliminated with a mean half-life of 6.5 days. After SC administration of 1 mg/kg, Ixekizumab reaches an average maximal plasma concentration of 11.1 µg/mL ~72 hours postdose. The mean elimination half-life following the SC injection was 10.3 days^[1].