WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 555388
Description: TP0463518 is a novel, highly potent HIF prolyl hydroxylase (PHD) inhibitor. TP0463518 competitively inhibited human PHD2 with a Ki value of 5.3 nM. TP0463518 also inhibited human PHD1/3 with IC50 values of 18 and 63 nM as well as monkey PHD2 with an IC50 value of 22 nM. In normal mice and rats, TP0463518 significantly increased the serum EPO levels at doses of 5 and 20 mg/kg, respectively.
MedKoo Cat#: 555388
Chemical Formula: C20H18ClN3O6
Exact Mass: 431.0884
Molecular Weight: 431.829
Elemental Analysis: C, 55.63; H, 4.20; Cl, 8.21; N, 9.73; O, 22.23
Synonym: TP0463518; TP-0463518; TP 0463518;
IUPAC/Chemical Name: (1-((6-(4-chlorophenoxy)pyridin-3-yl)methyl)-4-hydroxy-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonyl)glycine
InChi Key: HMMHKGLPKAQOOH-UHFFFAOYSA-N
InChi Code: InChI=1S/C20H18ClN3O6/c21-13-2-4-14(5-3-13)30-16-6-1-12(9-22-16)11-24-8-7-15(25)18(20(24)29)19(28)23-10-17(26)27/h1-6,9,25H,7-8,10-11H2,(H,23,28)(H,26,27)
SMILES Code: O=C(O)CNC(C1=C(O)CCN(CC2=CC=C(OC3=CC=C(Cl)C=C3)N=C2)C1=O)=O
The correlation factors for serum EPO and the serum TP0463518 levels were 0.95 in mice and 0.92 in rats. TP0463518 also increased the serum EPO level in 5/6 nephrectomized chronic kidney disease model rats at a dose of 10 mg/kg, with a correlation factor for serum EPO and the serum TP0463518 levels of 0.82. Finally, the effect of TP0463518 in monkeys was investigated. TP0463518 was promptly removed with a half-life of 5.2 h and increased the area under the curve (AUC) of EPO at a dose of 5 mg/kg. The EPO and TP0463518 levels were also correlated. P0463518 induces endogenous EPO with a strong pharmacokinetic-pharmacodynamic correlation and may contribute to desirable hemoglobin control in patients with renal anemia.
1: Kato S, Takayama N, Takano H, Koretsune H, Koizumi C, Kunioka EI, Uchida S,
Takahashi T, Yamamoto K. TP0463518, a novel inhibitor for hypoxia-inducible
factor prolyl hydroxylases, increases erythropoietin in rodents and monkeys with
a good pharmacokinetics-pharmacodynamics correlation. Eur J Pharmacol. 2018 Nov
5;838:138-144. doi: 10.1016/j.ejphar.2018.08.044. Epub 2018 Sep 1. PubMed PMID:
2: Shinfuku A, Shimazaki T, Fujiwara M, Sato F, Watase H, Numazaki T, Kawakita Y,
Mutoh M, Yamasaki H, Takayama N, Kato S, Sugimoto T, Maruyama J. Novel Compound
Induces Erythropoietin Secretion through Liver Effects in Chronic Kidney Disease
Patients and Healthy Volunteers. Am J Nephrol. 2018;48(3):157-164. doi:
10.1159/000492181. Epub 2018 Sep 3. PubMed PMID: 30176654; PubMed Central PMCID: