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 (Ki=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].

Product Specifications

CAS Number

[1558021-37-6]

UNSPSC

12352005

Hazard Statement

H302, H315, H319, H335

Target

HIF/HIF Prolyl-Hydroxylase

Type

Reference compound

Related Pathways

Metabolic Enzyme/Protease

Applications

Metabolism-sugar/lipid metabolism

Field of Research

Metabolic Disease; Inflammation/Immunology

Assay Protocol

https://www.medchemexpress.com/TP0463518.html

Purity

99.25

Solubility

DMSO : ≥ 125 mg/mL

Smiles

ClC(C=C1)=CC=C1OC2=NC=C(CN3C(C(C(NCC(O)=O)=O)=C(O)CC3)=O)C=C2

Molecular Formula

C20H18ClN3O6

Molecular Weight

431.83

Precautions

H302, H315, H319, H335

References & Citations

[1]Kato S, et al. 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.|[2]Kato S, et al. TP0463518 (TS-143) Ameliorates Peptidoglycan-Polysaccharide Induced Anemia of Inflammation in Rats. Biol Pharm Bull. 2021;44 (11) :1653-1661.