A non-peptide compound which can mimic the effect of thrombopoietin via c-Mpl.
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.
Kimura
T
T
Research and Development Division, Hokuriku Seiyaku Co., Ltd, Katsuyama, Fukui, Japan. tki@land.hokuriku.or.jp
Kaburaki
H
H
Tsujino
T
T
Ikeda
Y
Y
Kato
H
H
Watanabe
Y
Y
D001570:Benzodiazepinones / Q000737:chemistry / Q000494:pharmacology*; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007938:Leukemia; D008533:Megakaryocytes / Q000187:drug effects / Q000502:physiology; D008894:Milk Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D018121:Receptors, Cytokine / Q000378:metabolism; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D050799:STAT5 Transcription Factor; D013926:Thrombopoietin / Q000378:metabolism* / Q000494:pharmacology*; D015534:Trans-Activators / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001570:Benzodiazepinones; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; C082218:MPL protein, human; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013926:Thrombopoietin