LY364947

LY-364947 is a selective, ATP-competitive inhibitor of Transforming Growth Factor-β Type I receptor kinase. LY364947 inhibits TGF-β-dependent luciferase production in mink lung cells (p3TP lux) and growth in mouse fibroblasts (NIH 3T3) (IC50 values are 47 and 89 nM respectively). LY364947 is much less potent at related kinases, with IC50 of 400 nM for TGF-β RII and IC50 of 1400 nM for mixed lineage kinase-7 (MLK-7), a kinase in the MAP kinase signal pathway and closely related to TGF-β RII. LY364947 (3 μM) induces expression of Prox1 and LYVE-1 in almost all HDLECs after 24 hours. LY364947 (25 mg/kg) increases p-Akt and decreases nuclear Foxo3a in leukaemia-initiating cells in CML-affected mice.