Fig 1.

Janus kinase (JAK) inhibitors (JAKi) block the activity of cytokines. (A) Greater than 50 cytokines signal via the JAK-signal transducer and activator of transcription proteins (STAT) pathway and rely entirely on the kinase activity of JAK proteins to transmit their signals. JAK inhibitors block the activity of activated JAK proteins downstream of cytokine receptor signaling and thus prevent downstream activation of STAT proteins. (B) JAK inhibitors are oral medications dosed 1 to 2 times per day. The levels of drug in the plasma fluctuate throughout the day. During peak plasma levels a portion, but not all, of a particular cytokine's activity is inhibited. In practice, in this therapeutic range, pathologically elevated cytokine activity is targeted while normal cytokine function is relatively spared. Throughout the day, the plasma concentration is also frequently subtherapeutic. The specific range varies for individual cytokines and the specificity of the JAK inhibitor. Upon cessation of the drug, the effect dissipates rapidly.