ATC Group: L01EJ Janus-associated kinase (JAK) inhibitors

Fedratinib is a kinase inhibitor with activity against wild type and mutationally activated Janus Associated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3). Fedratinib reduced JAK2-mediated phosphorylation of signal transducer and activator of transcription (STAT3/5) proteins, inhibited malignant cell proliferation in vitro and in vivo.

Momelotinib and its major human circulating metabolite (M21), are inhibitors of wild type Janus Kinase 1 and 2 (JAK1/JAK2) and mutant JAK2^V617F, which contribute to signalling of a number of cytokines and growth factors that are important for haematopoiesis and immune function. Momelotinib inhibits cytokine-induced STAT3 phosphorylation in whole blood from patients with myelofibrosis and inhibits hepcidin. Additionally, momelotinib and M21 are direct inhibitors of ACVR1, which further down regulates liver hepcidin expression resulting in increased iron availability and red blood cell production.

Ruxolitinib is a selective inhibitor of the Janus Associated Kinases (JAKs) JAK1 and JAK2 (IC₅₀ values of 3.3 nM and 2.8 nM for JAK1 and JAK2 enzymes, respectively). These mediate the signalling of a number of cytokines and growth factors that are important for haematopoiesis and immune function. Ruxolitinib inhibits cytokine-induced STAT3 phosphorylation in whole blood from healthy subjects, MF patients and PV patients.