Chemical Component Summary

NameVadadustat
SynonymsGSK128863
Identifiers2-[[5-(3-chlorophenyl)-3-oxidanyl-pyridin-2-yl]carbonylamino]ethanoic acid
FormulaC14 H11 Cl N2 O4
Molecular Weight306.701
TypeNON-POLYMER
Isomeric SMILESc1cc(cc(c1)Cl)c2cc(c(nc2)C(=O)NCC(=O)O)O
InChIInChI=1S/C14H11ClN2O4/c15-10-3-1-2-8(4-10)9-5-11(18)13(16-6-9)14(21)17-7-12(19)20/h1-6,18H,7H2,(H,17,21)(H,19,20)
InChIKeyJGRXMPYUTJLTKT-UHFFFAOYSA-N

Chemical Details

Formal Charge0
Atom Count32
Chiral Atom Count0
Bond Count33
Aromatic Bond Count12

Drug Info: DrugBank

DrugBank IDDB12255 
NameVadadustat
Groups
  • approved
  • investigational
DescriptionOne of the most common symptoms of advanced renal disease is anemia, caused primarily by the inability of the kidney to respond to anemic conditions with a corresponding increase in [erythropoietin] (EPO) production.[A244165] The treatment of anemia associated with chronic kidney disease (CKD) has traditionally involved the administration of exogenous erythropoiesis-stimulating agents (ESAs), such as [darbepoetin alfa], to counter the decrease in endogenous EPO production. While efficacious, the overuse of ESAs has been associated with cardiovascular complications, progression of CKD, and increases in overall mortality.[A244165] A relatively new and alternative treatment option for patients with anemia associated with CKD is the use of small molecule inhibitors of hypoxia-inducible factor prolyl-hydroxylase (HIF-PH). These agents inhibit prolyl-hydroxylase domain oxygen sensors, mimicking hypoxic conditions and activating hypoxia-inducible factors. These transcription factors serve a multitude of roles, including the stimulation of erythropoiesis.[A244165] Vadadustat is an orally administered inhibitor of HIF-PH with a safety and efficacy profile non-inferior to [darbepoetin alfa] for the treatment of anemia in patients with CKD undergoing dialysis.[A244145,A244155] It was first approved in Japan, and in April 2023, it was approved by the EMA for the treatment of symptomatic anemia associated with CKD in adults on chronic maintenance dialysis.[L39610,L46936,L46951] Vadadustat is currently awaiting a regulatory decision by the FDA.[L39605] Vadadustat did not meet the prespecified noninferiority criterion for cardiovascular safety in patients with non-dialysis-dependent CKD.[A244150]
Synonyms
  • N-(5-(3-Chlorophenyl)-3-hydroxypyridine-2-carbonyl)glycine
  • Glycine, N-((5-(3-chlorophenyl)-3-hydroxy-2-pyridinyl)carbonyl)-
  • Vadadustat
Brand NamesVafseo
IndicationVadadustat is indicated for the treatment of symptomatic anemia associated with chronic kidney disease (CKD) in adults on chronic maintenance dialysis.[L46936]
Categories
  • Amino Acids
  • Amino Acids, Peptides, and Proteins
  • Antianemic Preparations
  • BCRP/ABCG2 Inhibitors
  • Blood and Blood Forming Organs
ATC-CodeB03XA08
CAS number1000025-07-9

Drug Targets

NameTarget SequencePharmacological ActionActions
Egl nine homolog 1MANDSGGPGGPSPSERDRQYCELCGKMENLLRCSRCRSSFYCCKEHQRQD...unknowninhibitor
Egl nine homolog 2MDSPCQPQPLSQALPQLPGSSSEPLEPEPGRARMGVESYLPCPLLPSYHC...unknowninhibitor
Egl nine homolog 3MPLGHIMRLDLEKIALEYIVPCLHEVGFCYLDNFLGEVVGDCVLERVKQL...unknowninhibitor
Hypoxia-inducible factor 1-alphaMEGAGGANDKKKISSERRKEKSRDAARSRRSKESEVFYELAHQLPLPHNV...unknownstabilization
Endothelial PAS domain-containing protein 1MTADKEKKRSSSERRKEKSRDAARCRRSKETEVFYELAHELPLPHSVSSH...unknownstabilization
View More
Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS. Nucleic Acids Res. 2011 Jan; 39 (Database issue):D1035-41. | PMID:21059682

Related Resource References

Resource NameReference
Pharos CHEMBL3646221
PubChem 23634441
ChEMBL CHEMBL3646221