Sigma-Aldrich Avatrombopag

Avatrombopag (E5501; YM477; AKR 501) is an orally active, potent, and humanand chimpanzee species-specific thrombopoietin (TPO) receptor (TPOR) agonistthat induces cellular STAT3/5 phosphorylation and proliferation ofhTPOR-expressing Ba/F3 cells (proliferation EC50 = 3.3 nM). Avatrombopagpromotes megakaryocyte differentiation from human cord blood (CB) CD34+ cells(EC50 = 25 nM) and increases the number of human platelets in NOD/SCID micetransplanted with human fetal liver CD34(+) cells in vivo (0.3, 1, 3 mg/kg/d p.o.). Thissmall molecule agonist of the TPO‐RAenhances platelet production by activating the receptor and mimicking thebiological effects of thrombopoietin (TPO). Its distinctive chemical structureallows 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 thephosphorylation of STAT3, STAT5, and ERK (MAPK), which promote thedifferentiation and proliferation of megakaryocytes, a vital process forplatelet production.

Avatrombopag may beused in laboratory studies to explore the mechanisms of thrombopoiesis and therole of thrombopoietin receptor agonists in platelet production.

Orally active, potent and human and chimpanzee species-specific thrombopoietin receptor (TPO) agonist in vitro and in vivo.