KT474

KT474 is a proteolysis-targeting chimera (PROTAC) that drives the degradation of IL-1 receptor-associated kinase 4 (IRAK4). It induces the degradation of IRAK4 in primary mouse and rat splenocytes and isolated dog, monkey, and human peripheral blood mononuclear cells (PBMCs) with half-maximal degradation concentration (DC50) values of 4. 2. 9. 2. and 1. nM, respectively. KT474 is selective for IRAK4 over a panel of 468 kinases at 1 µM. It inhibits IL-8 release induced by R-848 (Cay-14806) in isolated human PBMCs (IC50 = 3 nM). In vivo, KT474 (30 and 100 mg/kg, p.o.) decreases ear thickness in a mouse model of psoriasis induced by imiquimod (Cay-14956).. Solulibility: Acetonitrile: Slightly soluble: 0.1-1 mg/ml: DMSO: Sparingly soluble: 1-10 mg/ml.