TG101209 (SAR-317461) is a potent, selective, orally bioavailable JAK2 inhibitor with IC50 of 6 nM.
TG101209 also inhibits FLT3 (IC50=25 nM) and RET (IC50=17 nM) kinases, weakly inhibits JAK3 (IC50=168 nM).
TG101209 inhibits growth of Ba/F3 cells expressing JAK2V617F or MPLW515L mutations with IC50 of 200 nM, induces cell cycle arrest and apoptosis, and inhibits phosphorylation of JAK2V617F, STAT5 and STAT3.
TG101209 attenuates myelofibrosis in murine model of JAK2V617F-induced polycythemia vera.
TG101209 also potently inhibits BRD4 with Kd of 123 nM.
