Key result
A non-peptide benzodiazepinone compound stimulated the proliferation and STAT5 activation of a human TPO-dependent megakaryocytic cell line, mimicking the effect of thrombopoietin via c-Mpl.
Identifies a non-peptide compound capable of mimicking thrombopoietin effects via the c-Mpl receptor in vitro.
Supports development of non-peptide TPO receptor agonists; leaves open in vivo efficacy and safety for clinical use.
Thrombopoietin (TPO) is a cytokine which plays a central role in megakaryopoiesis and platelet production by binding to its cell surface receptor, termed c-Mpl. In the present study, two benzodiazepinones that compete with the binding of TPO to the extracellular region of c-Mpl were identified, and one of them stimulated the proliferation of a human 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 mimic the effect of TPO via c-Mpl.
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Kimura et al. (1998) studied this question. Benzodiazepinones was evaluated on Proliferation of UT-7/TPO cells and activation of STAT5. A non-peptide benzodiazepinone compound stimulated the proliferation and STAT5 activation of a human TPO-dependent megakaryocytic cell line, mimicking the effect of thrombopoietin via c-Mpl.
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