TG101348

TG101348 is an inhibitor of Janus kinase 2 (JAK2) with an IC₅₀ of 6 nM. It also inhibits related kinases fms-related tyrosine kinase 3 (FLT3), RET, and JAK3 with less potent activity, having IC₅₀ values of 25, 17 and 169 nM, respectively (Pardanani et al.). It is proposed to bind to the ATP binding pocket of its kinase targets (Zhou et al.).

CANCER RESEARCH

• Inhibits growth of Ba/F3 cells expressing JAK2 V617F or MPL W515L mutations (Pardanani et al.).
• Reduces tumor cell burden and increases survival in mouse models of JAK2 V617F-induced hematopoietic and myeloproliferative disease (Pardanani et al.; Wernig et al.).
• Sensitizes erlotinib-resistant non-small cell lung cancer cells to erlotinib treatment in vitro and in a mouse xenograft model (Zhang et al.).
• Displaces BRD4 from chromatin and suppresses c-MYC expression in multiple myeloma cells in vitro (Ciceri et al.).