Discovery of novel non-peptide thrombopoietin mimetic compounds that induce megakaryocytopoiesis
Bioscience Reports, ISSN: 0144-8463, Vol: 28, Issue: 5, Page: 275-285
2008
- 6Citations
- 4Captures
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Metrics Details
- Citations6
- Citation Indexes6
- CrossRef6
- Captures4
- Readers4
Article Description
We have identified a series of novel non-peptide compounds that activate the thrombopoietin-dependent cell line Ba/F3-huMPL. The compounds stimulated proliferation of Ba/F3-huMPL in the absence of other growth factors, but did not promote proliferation of the thrombopoietin-independent parent cell line Ba/F3. The thrombopoietin-mimetic compounds elicited signal-transduction responses comparable with recombinant human thrombopoietin, such as tyrosine phosphorylation of the thrombopoietin receptor, JAK (Janus kinase) 2, Tyk2 (tyrosine kinase 2), STAT (signal transducer and activator of transcription) 3, STAT5, MAPKs (mitogen-activated protein kinases), PLC? (phospholipase C?), Grb2 (growth-factor-receptor-bound protein 2), Shc (Src homology and collagen homology), Vav, Cbl and SHP- 2 (Src homology 2 domain-containing protein tyrosine phosphatase 2) and increased the number of CD41+ cells (megakaryocyte lineage) in cultures of human CD34+ bone-marrow cells (haematopoietic stem cells). These findings suggest that this series of compounds are novel agonists of the human thrombopoietin receptor and are possible lead compounds for the generation of anti-thrombocytopaenia drugs.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=65849148342&origin=inward; http://dx.doi.org/10.1042/bsr20080086; http://www.ncbi.nlm.nih.gov/pubmed/18620546; http://bioscirep.org/cgi/doi/10.1042/BSR20080086; https://portlandpress.com/bioscirep/article/28/5/275/55604/Discovery-of-novel-non-peptide-thrombopoietin; https://dx.doi.org/10.1042/bsr20080086; https://portlandpress.com/bioscirep/article-abstract/28/5/275/55604/Discovery-of-novel-non-peptide-thrombopoietin?redirectedFrom=fulltext
Portland Press Ltd.
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