TG101348 is an orally-available, aminopyrimidine-based inhibitor of JAK2 and JAK2V617F at an IC50 of 3 nM, with marked selectivity over JAK3 (IC50 >1 uM). [1, 2] TG101348 inhibits proliferation of HMC-1.1 and HMC-1.2 cells at IC50s of 740 and 407 nM, respectively. [1]

In a UT7/EPO cell line, TG101348 inhibited STAT5 phosphorylation much more potently at lower concentrations than known JAK2/3 inhibitor AG490 (600 nM vs 100 uM). In the same study, TG101348 inhibited AKT phosphorylation while reducing GATA-1 S310 phosphorylation. [2]

In human erythroleukemia and Ba/F3-JAK2V617F cells, TG101348 inhibited the cytokine-independent growth at IC50s of 300 and 580 nM, respectively. [3]

TG101348 induces apoptosis in both HEL and Ba/F3 JAK2V617F cells, but not in normal human dermal fibroblasts at concentrations up to 10 uM; antiproliferative IC50 against fibroblasts is > 5 uM.