Tofacitinib inhibits IL-2-mediated human T cell blast proliferation and IL-15-induced CD69 expression with IC50 of 11 nM and 48 nM, respectively. Tofacitinib prevents mixed lymphocyte reaction with IC50 of 87 nM. Tofacitinib treatment of murine factor-dependent cell Patersen�Cerythropoietin receptor (FDCP-EpoR) cells harboring human wild-type or V617F JAK2 leads to prevention of cell proliferation with IC50 of 2.1 µM and 0.25 µM, respectively. Tofacitinib inhibits interleukin-6-induced phosphorylation of STAT1 and STAT3 with IC50 of 23 nM and 77 nM, respectively. Moreover, Tofacitinib generates a significant pro-apoptotic effect on murine FDCP-EpoR cells carrying JAK2VV617F, whereas a lesser effect was observed for cells carrying wild-type JAK2. This activity is coupled with the inhibition of phosphorylation of the key JAK2V617F-dependent downstream signaling effectors signal transducer and activator of transcription (STAT)3, STAT5, and v-akt murine thymoma viral oncogene homolog (AKT).

(3R,4S)-Tofacitinib

(3S,4R)-Tofacitinib

(3S,4S)-Tofacitinib

AG-490

AT9283

AZD-1480

Baricitinib

BMS-911543

CEP-33779