TP0463518

TP0463518 is an orally active, competitive pan-inhibitor of hypoxia-inducible factor prolyl hydroxylases PHD1/2/3. TP0463518 competitively inhibits human PHD1 (IC₅₀=18 nM), PHD2 (K_i=5.3 nM), and PHD3 (IC₅₀=63 nM), and targets monkey PHD2 with an IC₅₀ of 22 nM. TP0463518 inhibits PHD-catalyzed hydroxylation to stabilize HIFα, thereby upregulating erythropoietin (EPO) expression and enhancing intestinal iron absorption (such as increased DMT-1 and dCYTb expression), improving anemia. TP0463518 is mainly used for the research of renal anemia and inflammatory anemia^[1][2]. In Vitro:TP0463518 can significantly upregulate the mRNA expression of the HIF-2α target gene EPO in 293FT cells, with liver-specific induction of EPO by 5.2-fold^[1]. In Vivo:TP0463518 (5-40 mg/kg; oral gavage; once daily; 6 weeks) significantly increases serum erythropoietin (EPO) levels and improved renal anemia and inflammatory anemia in mice, rats, 5/6 nephrectomized rats and rhesus monkey models, and the blood drug concentration is highly correlated with EPO levels^[1][2].