Avatrombopag (AKR-501) is an orally active, nonpeptide thrombopoietin (TPO) receptor agonist with an EC50 of 3.3 nM. It mimics the biological activities of TPO, stimulating platelet production by activating the intracellular signaling system and promoting the generation of platelets and megakaryocytes from hematopoietic precursor cells. Avatrombopag is metabolized by cytochrome P450 (CYP) 2C9 and CYP3A enzymes [1][2][3].
体内研究
Avatrombopag (0.3-3 mg/kg; pO.; daily for 14 days) enhances human platelet count in NOD/SCID mice that have been transplanted with human FL CD34+ cells [1].
体外研究
Avatrombopag (E5501; AKR-501) selectively binds to the TPO receptor and induces megakaryocytopoiesis during the development and maturation of megakaryocytes, akin to the effect of recombinant human TPO (rhTPO) [1].
Avatrombopag (0-100 nM) promotes the proliferation of Ba/F3 cells expressing the TPO receptor in a concentration-dependent manner. Furthermore, Avatrombopag (0-3 μM) induces tyrosine phosphorylation of STAT3 and STAT5, as well as threonine phosphorylation of ERK in these cells, similar to the effects observed with rhTPO [1].
Avatrombopag induces concentration-dependent formation of megakaryocyte colonies from human CB CD34+ cells. The EC50 for Avatrombopag is 25 nM, and its maximum activity is comparable to that of rhTPO [1].
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