Reference - Detail
| RRC ID | 42560 |
|---|---|
| Author | Nakamura T, Miyakawa Y, Miyamura A, Yamane A, Suzuki H, Ito M, Ohnishi Y, Ishiwata N, Ikeda Y, Tsuruzoe N. |
| Title | A novel nonpeptidyl human c-Mpl activator stimulates human megakaryopoiesis and thrombopoiesis. |
| Journal | Blood |
| Abstract |
NIP-004 is a novel synthetic compound developed to display human thrombopoietin (TPO) receptor (c-Mpl) agonist activity. NIP-004 displays species specificity, stimulating proliferation or differentiation of human c-Mpl-expressing cells such as UT-7/TPO and human CD34(+) cells but not murine c-Mpl-expressing cells or cynomolgus monkey cells. To test the mechanism of its action, we constructed mutant forms of c-Mpl; murine c-Mpl(L490H) dis-played a response to NIP-004, whereas human c-Mpl(H499L) lost this response, indicating that histidine in the transmembrane domain of c-Mpl is essential for its activity. Because histidine is not present in the c-Mpl transmembrane domain of rats, hamsters, rhesus macaques, and cynomolgus monkeys, we examined the in vivo efficacy of NIP-004 using mice that received xenotransplants. In immunodeficient nonobese diabetic (NOD)/Shi-scid, IL-2Rgamma(null) (NOG) mice receiving transplants of umbilical cord blood-derived CD34(+) cells, NIP-004 increased human megakaryoblasts, mature megakaryocytes, and circulating human platelets 6-fold, the latter being morphologically and functionally indistinguishable from normal human platelets. These observations indicate that NIP-004 is a novel human c-Mpl activator and induces human thrombopoiesis. |
| Volume | 107(11) |
| Pages | 4300-7 |
| Published | 2006-6-1 |
| DOI | 10.1182/blood-2005-11-4433 |
| PII | S0006-4971(20)64564-5 |
| PMID | 16484588 |
| MeSH | Animals Blood Platelets / cytology Cell Count Cell Line, Tumor Cord Blood Stem Cell Transplantation Graft Survival Histidine Humans Megakaryocytes / cytology Mice Mice, SCID Mutation Proto-Oncogene Proteins / agonists* Proto-Oncogene Proteins / genetics Receptors, Cytokine / agonists* Receptors, Cytokine / genetics Receptors, Thrombopoietin Thrombopoiesis / drug effects* Transplantation, Heterologous |
| IF | 17.794 |
| Times Cited | 58 |
| WOS Category | HEMATOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 24 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | Ba/F3(RCB0805) |