TG-101348 also significantly inhibits JAK2 V617F, Flt3, and Ret with IC50 of 3 nM, 15 nM, and 48 nM, respectively. TG-101348 also inhibits proliferation of parental Ba/F3 cells to a comparable level, with IC50 of ~420 nM. TG101348 treatment decreases GATA-1 expression, which is associated with erythroid-skewing of JAK2V617F+ progenitor differentiation, and inhibits STAT5 as well as GATA S310 phosphorylation.
In vivo
Oral administration of TG101348 (120 mg/kg) significantly inhibits PV progenitor erythroid differentiation in vivo.
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