Vadadustat

Summary

Vadadustat (CHEMBL3646221) is an approved small molecule (ATC B03XA08) targeting EGLN2 and EGLN1; indicated across 4 conditions including anemia and chronic kidney disease.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: B03XA08
• Targets: 2 (EGLN2, EGLN1)
• Indications: 4 conditions
• Clinical trials: 35
• Chemistry: 306.7 Da · C14H11ClN2O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3646221
Name	Vadadustat
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	23634441
ATC	B03XA08
Molecular formula	C14H11ClN2O4
Molecular weight	306.7
InChIKey	JGRXMPYUTJLTKT-UHFFFAOYSA-N

SMILES: C1=CC(=CC(=C1)Cl)C2=CC(=C(N=C2)C(=O)NCC(=O)O)O

IUPAC name: 2-[[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino]acetic acid

Also known as: AKB-6548, B-506, B506, PG-1016548, PG1016548, Vadadustat, Vafseo, VADADUSTAT

Patent coverage: 207 distinct patent families (533 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 347 (65%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
EGLN2	egl-9 family hypoxia inducible factor 2	Inhibition		4.6%	Q96KS0
EGLN1	egl-9 family hypoxia inducible factor 1	Inhibition	7.54	16.6%	Q9GZT9

Broader ChEMBL bioactivity targets: 12 (assay-derived). Sample: Vascular endothelial growth factor A, long form, Vascular endothelial growth factor receptor 1, Gamma-butyrobetaine dioxygenase, Methylcytosine dioxygenase TET2, Bifunctional peptidase and arginyl-hydroxylase JMJD5, Prolyl 3-hydroxylase OGFOD1, Methylcytosine dioxygenase TET1, Aspartyl/asparaginyl beta-hydroxylase, Methylcytosine dioxygenase TET3, Egl nine homolog 1, Prolyl hydroxylase EGLN3, Hypoxia-inducible factor 1-alpha inhibitor.

Bioactivity

ChEMBL activities: 26 potent at pChembl ≥ 5 of 29 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
EGLN1	7.54	IC50	29	nM	CHEMBL_ACT_18989068
EGLN1	7.54	IC50	29	nM	CHEMBL_ACT_24960818
EGLN1	6.59	IC50	256.9	nM	CHEMBL_ACT_25510258
BBOX1	6.55	IC50	280	nM	CHEMBL_ACT_29204381
EGLN3	6.41	IC50	390	nM	CHEMBL_ACT_16311771
EGLN3	6.41	IC50	390	nM	CHEMBL_ACT_16333476
EGLN1	6.41	IC50	390	nM	CHEMBL_ACT_16761070
EGLN3	6.41	IC50	390	nM	CHEMBL_ACT_27022829
EGLN3	6.41	IC50	390	nM	CHEMBL_ACT_28782323
EGLN1	6.39	IC50	410	nM	CHEMBL_ACT_16300587
EGLN1	6.39	IC50	410	nM	CHEMBL_ACT_16338084
EGLN1	6.39	IC50	410	nM	CHEMBL_ACT_27022823
EGLN1	6.39	IC50	410	nM	CHEMBL_ACT_28782314
EGLN1	6	IC50	990	nM	CHEMBL_ACT_29204430
EGLN1	5.96	IC50	1100	nM	CHEMBL_ACT_16279408
EGLN1	5.96	IC50	1100	nM	CHEMBL_ACT_16317896
EGLN1	5.96	IC50	1100	nM	CHEMBL_ACT_27022826
EGLN1	5.96	IC50	1100	nM	CHEMBL_ACT_28782320
OGFOD1	5.85	IC50	1400	nM	CHEMBL_ACT_18989078
KDM8	5.39	IC50	4100	nM	CHEMBL_ACT_29204510
ASPH	5.36	IC50	4400	nM	CHEMBL_ACT_29204501
TET2	5.3	IC50	5012	nM	CHEMBL_ACT_25520051
TET3	5.26	IC50	5495	nM	CHEMBL_ACT_25520085
TET1	5.2	IC50	6310	nM	CHEMBL_ACT_25520016
VEGFA	5.12	EC50	7600	nM	CHEMBL_ACT_17616023
FLT1	5.12	EC50	7600	nM	CHEMBL_ACT_28782317

Target pathways

Aggregated over 2 target gene(s): EGLN2, EGLN1.

Top Reactome pathways

1 total, by targets touching each:

Pathway	Targets	Genes
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	2	EGLN1, EGLN2

Dominant GO biological processes

GO term	Targets
response to hypoxia	2
regulation of neuron apoptotic process	2
cellular response to hypoxia	2
regulation of cell growth	1
peptidyl-proline hydroxylation to 4-hydroxy-L-proline	1
estrogen receptor signaling pathway	1
cell redox homeostasis	1
positive regulation of protein catabolic process	1
intracellular iron ion homeostasis	1
intracellular oxygen homeostasis	1
regulation of angiogenesis	1
positive regulation of transcription by RNA polymerase II	1
cardiac muscle tissue morphogenesis	1
heart trabecula formation	1
ventricular septum morphogenesis	1

Indications & clinical

Indications

2 approved indications. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
anemia	4	MONDO:0002280	EFO:0004272
chronic kidney disease	4	MONDO:0005300	EFO:0003884

1 disease in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
liver disorder	1	MONDO:0005154	EFO:0001421

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 35.

Phase distribution

Phase	Trials
PHASE3	12
PHASE1	11
PHASE2	10
PHASE4	1
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07537816	PHASE4	NOT_YET_RECRUITING	Effects of Vadadustat on Anemia, Quality of Life, and Inflammation in Dialysis Patients
NCT06520826	PHASE3	ACTIVE_NOT_RECRUITING	Vafseo Outcomes In-Center Experience
NCT06901505	PHASE3	ACTIVE_NOT_RECRUITING	To Evaluate the Efficacy of Three Times Weekly (TIW) Vadadustat Compared to Standard of Care ESA in Patients With Anemia of CKD Receiving In-Center Hemodialysis
NCT07086755	PHASE2/PHASE3	RECRUITING	Vadadustat for the Treatment of Nonintubated Acute Respiratory Distress Syndrome Due to Pathogen-Associated Lung Injury
NCT07565701	PHASE3	NOT_YET_RECRUITING	Safety and Efficacy of a Phased Transition From Epogen to Three Times Weekly Oral Vadadustat for the Treatment of Anemia in Subjects Receiving In-Center Hemodialysis
NCT02648347	PHASE3	COMPLETED	Study to Evaluate Vadadustat for the Correction of Anemia in Participants With Non-dialysis-dependent Chronic Kidney Disease
NCT02680574	PHASE3	COMPLETED	Efficacy and Safety Study to Evaluate Vadadustat for the Maintenance Treatment of Anemia in Participants With Non-dialysis-dependent Chronic Kidney Disease (NDD-CKD)
NCT02865850	PHASE3	COMPLETED	Efficacy and Safety Study to Evaluate Vadadustat for the Correction or Maintenance Treatment of Anemia in Participants With Incident Dialysis-dependent Chronic Kidney Disease (DD-CKD)
NCT02892149	PHASE3	COMPLETED	Efficacy and Safety Study to Evaluate Vadadustat for the Maintenance Treatment of Anemia in Participants With Dialysis-dependent Chronic Kidney Disease (DD-CKD)
NCT03242967	PHASE3	WITHDRAWN	Study to Evaluate Three Times Per Week (TIW) Oral Dosing of Vadadustat for Anemia in Subjects With Dialysis-Dependent Chronic Kidney Disease (DD-CKD)
NCT04313153	PHASE3	COMPLETED	Trial Evaluating the Efficacy and Safety of Oral Vadadustat Once Daily (QD) and Three Times Weekly (TIW) for the Maintenance Treatment of Anemia in Hemodialysis Subjects Converting From Erythropoiesis-Stimulating Agents (ESAs)
NCT04707768	PHASE3	COMPLETED	Study Evaluating the Efficacy and Safety of Dose Conversion From a Long-acting Erythropoiesis-stimulating Agent (Mircera®) to Three Times Weekly Oral Vadadustat for the Maintenance Treatment of Anemia in Hemodialysis Subjects
NCT05082571	PHASE3	WITHDRAWN	Study to Evaluate the Safety and Efficacy of Oral Vadadustat in Pediatric Participants With Anemia of Chronic Kidney Disease
NCT05082584	PHASE3	WITHDRAWN	Study to Evaluate the Safety and Efficacy of Oral Vadadustat in Pediatric Participants With Anemia of Chronic Kidney Disease Naive to Erythropoiesis-Stimulating Agents
NCT01235936	PHASE2	COMPLETED	Safety and Efficacy Study for AKB-6548 in Participants With Chronic Kidney Disease and Anemia
NCT01381094	PHASE2	COMPLETED	42-Day Repeat Oral Dose Study of AKB-6548 in Participants With Chronic Kidney Disease and Anemia
NCT01906489	PHASE2	COMPLETED	20-Week Repeat Oral Dose Study of AKB-6548 in Participants With Chronic Kidney Disease and Anemia
NCT02260193	PHASE2	COMPLETED	16-Week Repeat Oral Dose Study of AKB-6548 for Anemia in Participants With End Stage Renal Disease (ESRD) Requiring Chronic Hemodialysis
NCT03054337	PHASE2	COMPLETED	Dose-Finding Study of Vadadustat in Japanese Subjects With Anemia Secondary to Non-Dialysis Dependent Chronic Kidney Disease (NDD-CKD)
NCT03054350	PHASE2	COMPLETED	Dose-Finding Study of Vadadustat in Japanese Subjects With Anemia Secondary to Dialysis-Dependent Chronic Kidney Disease (DD-CKD)
NCT03140722	PHASE2	TERMINATED	Study to Evaluate Vadadustat for Anemia in Subjects With Dialysis-Dependent Chronic Kidney Disease (DD-CKD) Who Are Hyporesponsive to Erythropoiesis Stimulating Agents
NCT03799627	PHASE2	COMPLETED	Study of Vadadustat in Hemodialysis Participants With Anemia Switching From Epoetin Alfa
NCT04478071	PHASE2	COMPLETED	Vadadustat for the Prevention and Treatment of Acute Respiratory Distress Syndrome (ARDS) in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19)
NCT04707573	PHASE2	COMPLETED	Study to Assess the Safety and Pharmacokinetics of AKB-6548 in Participants With Chronic Kidney Disease (CKD), Stages 3 and 4
NCT02327546	PHASE1	COMPLETED	Effects of Ferrous Sulfate on the Pharmacokinetics of AKB-6548
NCT02502500	PHASE1	COMPLETED	Effect of AKB-6548 on the Pharmacokinetics of Celecoxib
NCT03639155	PHASE1	COMPLETED	A Study in Evaluating Bioequivalence Between Test and Reference Formulations of Vadadustat Tablets in Healthy Adults
NCT03657290	PHASE1	COMPLETED	A Study in Evaluating Bioequivalence of Test and Reference Vadadustat 450 MG and 150 MG Tablets and to Determine Food Effect on the 450 MG Tablet
NCT03789032	PHASE1	COMPLETED	Study to Evaluate the Effect of Rabeprazole on the Pharmacokinetics of Vadadustat
NCT03799848	PHASE1	COMPLETED	A Single Dose Study of Oral Vadadustat in Subjects With Normal and Impaired Hepatic Function
NCT03801733	PHASE1	COMPLETED	Drug-Drug Interaction Study of Vadadustat With Rosuvastatin, Sulfasalazine, Pravastatin, Atorvastatin and Simvastatin
NCT03801746	PHASE1	COMPLETED	Drug-Drug Interaction Study of Vadadustat With Cyclosporine, Probenecid and Rifampin
NCT03801759	PHASE1	COMPLETED	Drug-Drug Interaction Study of Vadadustat With Digoxin, Adefovir and Furosemide
NCT03992066	PHASE1	COMPLETED	Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Vadadustat in Hemodialysis Subjects With Anemia Associated With Chronic Kidney Disease
NCT04299633	PHASE1	COMPLETED	Study in Healthy Adult Subjects to Assess the Effect of Phosphate Binders on the Pharmacokinetics of a Single Dose of Vadadustat

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

12 molecules share ≥1 primary target. Top 12 by shared-target count:

Molecule	Source	Status	Shared targets
MOLIDUSTAT	ChEMBL + PubChem	Phase 2 (approved)	EGLN1, EGLN2
anhydrous citric acid	PubChem	Approved	EGLN1, EGLN2
DAPRODUSTAT	ChEMBL	Phase 4 (approved)	EGLN1
ROXADUSTAT	ChEMBL	Phase 4 (approved)	EGLN1
DESIDUSTAT	ChEMBL	Phase 3	EGLN1
ENARODUSTAT	ChEMBL	Phase 3	EGLN1
FUMARIC ACID	ChEMBL	Phase 3	EGLN1
SUCCINIC ACID	ChEMBL	Phase 3	EGLN1
IZILENDUSTAT	ChEMBL	Phase 2	EGLN1
ascorbic acid	PubChem	Approved	EGLN2
Malic Acid	PubChem	Approved	EGLN2
Oxygen	PubChem	Approved	EGLN2