Emavusertib is an inhibitor of IL-1 receptor-associated kinase 4 (IRAK4; IC50 = 31.7 nM).1 It is selective for IRAK4 over FMS-related tyrosine kinase 3 (FLT3), cyclin-dependent kinase 2 (Cdk2), Aurora A kinase, glycogen synthase kinase 3β (GSK3β), and muscle-associated receptor tyrosine kinase (MUSK) at 1 µM. Emavusertib inhibits IL-6 release mediated by toll-like receptor 2 (TLR2), TLR5, or IL-1 receptor (IL-1R) in isolated human whole blood (IC50s = 989, 696, and 1,375 nM, respectively). In vivo, emavusertib (25-200 mg/kg) reduces tumor volume in an OCI-Ly3 diffuse large B cell lymphoma (DLBCL) mouse xenograft model.
1.Gummadi, V.R., Boruah, A., Ainan, B.R., et al.Discovery of CA-4948, an orally bioavailable IRAK4 inhibitor for treatment of hematologic malignanciesACS Med. Chem. Lett.11(12)2374-2381(2020)