Application
Avatrombopag may be used in laboratory studies to explore the mechanisms of thrombopoiesis and the role of thrombopoietin receptor agonists in platelet production.
Biochem/physiol Actions
Avatrombopag (E5501; YM477; AKR 501) is an orally active, potent, and human and chimpanzee species-specific thrombopoietin (TPO) receptor (TPOR) agonist that induces cellular STAT3/5 phosphorylation and proliferation of hTPOR-expressing Ba/F3 cells (proliferation EC50 = 3.3 nM). Avatrombopag promotes megakaryocyte differentiation from human cord blood (CB) CD34+ cells (EC50 = 25 nM) and increases the number of human platelets in NOD/SCID mice transplanted with human fetal liver CD34(+) cells in vivo (0.3, 1, 3 mg/kg/d p.o.). This small molecule agonist of the TPO‐RA enhances platelet production by activating the receptor and mimicking the biological effects of thrombopoietin (TPO). Its distinctive chemical structure allows for selective binding to the transmembrane domain of the TPO receptor (TPO-R), preventing interference with the binding of endogenous TPO. Avatrombopag activates crucial intracellular pathways, such as the phosphorylation of STAT3, STAT5, and ERK (MAPK), which promote the differentiation and proliferation of megakaryocytes, a vital process for platelet production.
Orally active, potent and human and chimpanzee species-specific thrombopoietin receptor (TPO) agonist in vitro and in vivo.
| Quality Segment | 100 |
| assay | ≥98% (HPLC) |
| form | powder |
| color | white to beige |
| solubility | DMSO: 2 mg/mL, clear (warmed) |
| storage temp. | 2-8°C |
| SMILES string | ClC1=CC(C(NC2=NC(C3=CC(Cl)=CS3)=C(N4CCN(C5CCCCC5)CC4)S2)=O)=CN=C1N6CCC(C(O)=O)CC6 |
