PlumX Metrics
Embed PlumX Metrics

Discovery of novel non-peptide thrombopoietin mimetic compounds that induce megakaryocytopoiesis

Bioscience Reports, ISSN: 0144-8463, Vol: 28, Issue: 5, Page: 275-285
2008
  • 6
    Citations
  • 0
    Usage
  • 4
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

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

Yamane, Noriko; Takahashi, Koji; Tanaka, Yoshikazu; Kato, Kazue; Takayama, Masami; Ohyabu, Naoki; Shiota, Takeshi; Takenaka, Hideyuki; Yoshida, Yutaka; Hara, Shinichiro; Murashi, Takami; Nakamura, Etsuo; Nishitani, Yoshinori; Ishizaki, Jun; Yamane, Shoji; Nagata, Kiyoshi; Koizumi, Kenzo; Yutsudo, Takashi; Suzuki, Ryuji; Itoh, Tsunetoshi; Takemoto, Hiroshi

Portland Press Ltd.

Biochemistry, Genetics and Molecular Biology

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know