A NONPEPTIDE COMPOUND WHICH CAN MIMIC THE EFFECT OF THROMBOPOIETIN VIA C-MPL

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.