product name Eltrombopag
Description: Eltrombopag, a member of the biarylhydrazone class, is a nonpeptide agonist of the thrombopoietin receptor (TpoR), used to treat chronic hepatitis C-associated thrombocytopenia and chronic immune (idiopathic) thrombocytopenia (ITP). Eltrombopag demonstrates an EC50 of 0.27 μM in murine BAF3 cells transfected with the luciferase reporter gene under direction of the STAT-activated IRF-1 promoter and human TpoR. Eltrombopag activates the receptor by association with metal ions (i.e., Zn2+) and specific amino acids within the transmembrane and juxtamembrane domains of the TpoR.
References: Stem Cells. 2009 Feb;27(2):424-30; Leuk Res. 2010 Sep;34(9):1224-31; Blood. 2012 Jul 12;120(2):386-94.
442.47
Formula
C25H22N4O4
CAS No.
496775-61-2
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 26 mg/mL (58.8 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: Eltrombopag demonstrates a half maximal effective concentration (EC50) of 0.27 μM in murine BAF3 cells transfected with the luciferase reporter gene under direction of the STAT-activated IRF-1 promoter and human TpoR (BAF3/IRF-1/hTpoR). Eltrombopag activates the receptor by association with metal ions (i.e., Zn2+) and specific amino acids within the transmembrane and juxtamembrane domains of the TpoR. Eltrombopag (30 μM) results in activation of STAT5 in N2C-Tpo cells, as detected with an antiphospho-STAT5 antibody on Western blots. Eltrombopag stimulates proliferation after a 2-day incubation with an EC50 of 0.03 μM in a BrdU assay conducted in BAF3/hTpoR cells. Eltrombopag also induces differentiation of hematopoietic stem cells into committed megakaryocyte progenitor cells. Eltrombopag increases the differentiation of bone marrow CD34+ cells into CD41+ megakaryocytes in a dose-dependent manner with an EC50 of 0.1 μM. Eltrombopag inhibits N2C-Tpo cell and HEL92.1.7 cell proliferating with IC50 of 20.7 μg/mL and 2.3 μg/mL. Eltrombopag (20 μg/mL) leads to a decreased cell division rate, a block in G(1) phase of cell cycle, and increased differentiation in human and murine leukemia cells. Eltrombopag (5 μg/mL) shows clear signs of differentiation, significant changes in the organization of the nuclear contents, and an increase in the cytoplasm/nucleus ratio in HL60 cells. Eltrombopag (5 μg/mL) causes an increase in CD11b, which is consistent with a premacrophage state in U937 cells, and also causes an increase in CD11b in URE cells. Eltrombopag leads to a reduction in free intracellular iron in leukemic cells in a dose-dependent manner in HL60 cells. Kinase Assay: Cell Assay: |
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| In Vivo | Eltrombopag (10 mg/kg per day) increases platelet counts over twofold approximately 1 week after the last dose for one chimpanzee and approximately 1.5-fold for the other two chimpanzees. Eltrombopag (1 mg/mL) prolongs survival in mouse models of leukemia. |
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| References | Stem Cells. 2009 Feb;27(2):424-30; Leuk Res. 2010 Sep;34(9):1224-31; Blood. 2012 Jul 12;120(2):386-94. |
