Avatrombopag

Avatrombopag (AKR-501) is an orally active, nonpeptide thrombopoietin (TPO) receptor agonist (EC₅₀=3.3 nM). Avatrombopag mimics the biological activities of TPO. Avatrombopag increases platelet production by activating the intracellular signaling system, and promotes production of platelets and megakaryocytes from hemopoietic precursor cells. Avatrombopag is a substrate of cytochrome P450 (CYP) 2C9 and CYP3A^[1][2][3]. IC50 & Target:EC50: 3.3 nM (TPO receptor)^[1] In Vitro:Avatrombopag (E5501; AKR-501) specifically targets the TPO receptor and stimulated megakaryocytopoiesis throughout the development and maturation of megakaryocytes just as recombinant human TPO (rhTPO) did^[1].
Avatrombopag (0-100 nM) supports the proliferation of TPO receptor expressing Ba/F3 cell in a concentration-dependent fashion. Avatrombopag (0-3 μM) induces tyrosine phosphorylation of STAT3 and STAT5, and threonine phosphorylation of ERK in the cells, as did rhTPO^[1].
Avatrombopag promotes megakaryocyte colony formation from human CB CD34⁺ cells in a concentration-dependent fashion. The EC₅₀ is 25 nM for Avatrombopag and the maximum activity of Avatrombopag is similar to that of rhTPO^[1]. In Vivo:Avatrombopag (0.3-3 mg/kg; p.o.; daily for 14 days) increases the number of human platelets in NOD/SCID mice transplanted with human FL CD34⁺ cells^[1].