Thrombopoietin (TPO) is a cytokine which plays a central role in megak
aryopoiesis and platelet production by binding to its cell surface rec
eptor, termed c-Mpl, In the present study, two benzodiazepinones that
compete with the binding of TPO to the extracellular region of c-Mpl w
ere identified, and one of them stimulated the proliferation of a huma
n TPO-dependent megakaryocytic cell line, UT-7/TPO. It stimulated the
activation of signal transducer and activator of transcription 5 in UT
-7/TPO cells, These results suggest that a non-peptide compound can mi
mic the effect of TPO via c-Mpl. (C) 1998 Federation of European Bioch
emical Societies.