Roxadustat

Summary

Roxadustat (CHEMBL2338329) is an approved small-molecule EC 1.14.11.2 (procollagen-proline dioxygenase) inhibitor (ATC B03XA05) targeting EGLN2; indicated across 5 conditions including anemia and chronic kidney disease.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: B03XA05
• Targets: 1 (EGLN2)
• Indications: 5 conditions
• Clinical trials: 63
• Chemistry: 352.3 Da · C19H16N2O5

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2338329
Name	Roxadustat
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	11256664
ChEBI	CHEBI:132774
ATC	B03XA05
Molecular formula	C19H16N2O5
Molecular weight	352.3
InChIKey	YOZBGTLTNGAVFU-UHFFFAOYSA-N

SMILES: CC1=C2C=C(C=CC2=C(C(=N1)C(=O)NCC(=O)O)O)OC3=CC=CC=C3

IUPAC name: 2-[(4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carbonyl)amino]acetic acid

ChEBI definition: An N-acylglycine resulting from the formal condensation of the amino group of glycine with the carboxy group of 4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carboxylic acid. It is an inhibitor of hypoxia inducible factor prolyl hydroxylase (HIF-PH).

Pharmacological roles (ChEBI): EC 1.14.11.2 (procollagen-proline dioxygenase) inhibitor, EC 1.14.11.29 (hypoxia-inducible factor-proline dioxygenase) inhibitor.

Also known as: ASP-1517, ASP1517, Evrenzo, FG-4592, FG4592, Roxadustat, ROXADUSTAT, SID174006837, roxadustat

Patent coverage: 471 distinct patent families (1,063 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 705 (66%) 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

Broader ChEMBL bioactivity targets: 9 (assay-derived). Sample: Thyroid hormone receptor alpha, Thyroid hormone receptor beta, Gamma-butyrobetaine dioxygenase, Sodium-dependent noradrenaline transporter, Alpha-ketoglutarate-dependent dioxygenase FTO, Sodium-dependent dopamine transporter, Bifunctional peptidase and arginyl-hydroxylase JMJD5, Aspartyl/asparaginyl beta-hydroxylase, Egl nine homolog 1.

Bioactivity

ChEMBL activities: 22 potent at pChembl ≥ 5 of 25 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
THRB	7.89	EC50	12.9	nM	CHEMBL_ACT_24922581
EGLN1	7.85	IC50	14	nM	CHEMBL_ACT_25962638
EGLN1	7.57	IC50	27	nM	CHEMBL_ACT_18989067
EGLN1	7.5	IC50	32	nM	CHEMBL_ACT_22951633
THRA	7.49	EC50	32.7	nM	CHEMBL_ACT_24922553
EGLN1	7.33	IC50	47	nM	CHEMBL_ACT_24922623
EGLN1	6.93	IC50	117.2	nM	CHEMBL_ACT_25510257
EGLN1	6.92	IC50	120.5	nM	CHEMBL_ACT_24821698
EGLN1	6.28	IC50	520	nM	CHEMBL_ACT_24887216
EGLN1	6.24	IC50	575.3	nM	CHEMBL_ACT_19130987
EGLN1	6.23	IC50	591.4	nM	CHEMBL_ACT_16483251
EGLN1	6.23	IC50	591.4	nM	CHEMBL_ACT_18299387
EGLN1	6.23	IC50	591	nM	CHEMBL_ACT_22401550
EGLN1	6.22	IC50	599	nM	CHEMBL_ACT_28222109
EGLN1	5.68	IC50	2100	nM	CHEMBL_ACT_17700696
EGLN1	5.68	IC50	2100	nM	CHEMBL_ACT_17765945
EGLN1	5.55	IC50	2800	nM	CHEMBL_ACT_29204493
SLC6A3	5.54	AC50	2880	nM	CHEMBL_ACT_25125381
EGLN1	5.24	IC50	5740	nM	CHEMBL_ACT_18299420
EGLN1	5.21	EC50	6110	nM	CHEMBL_ACT_24965174
BBOX1	5.09	IC50	8100	nM	CHEMBL_ACT_29204383
FTO	5.01	IC50	9800	nM	CHEMBL_ACT_12700016

Target pathways

Aggregated over 1 target gene(s): EGLN2.

Top Reactome pathways

1 total, by targets touching each:

Pathway	Targets	Genes
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	1	EGLN2

Dominant GO biological processes

GO term	Targets
regulation of cell growth	1
response to hypoxia	1
peptidyl-proline hydroxylation to 4-hydroxy-L-proline	1
estrogen receptor signaling pathway	1
regulation of neuron apoptotic process	1
cell redox homeostasis	1
positive regulation of protein catabolic process	1
cellular response to hypoxia	1

Indications & clinical

Indications

5 indications (2 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
anemia	4	MONDO:0002280	EFO:0004272
chronic kidney disease	4	MONDO:0005300	EFO:0003884
myelodysplastic syndrome	3	MONDO:0018881	EFO:0000198
ST-elevation myocardial infarction	2	MONDO:0041656	EFO:0008585
kidney disorder	1	MONDO:0005240	EFO:0003086

Clinical trials

Total trials: 63.

Phase distribution

Phase	Trials
PHASE3	24
PHASE2	13
PHASE1	12
PHASE4	8
Not specified	3
PHASE1/PHASE2	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07162090	PHASE4	NOT_YET_RECRUITING	Hypoxia-inducible Factor Prolyl Hydroxylase Inhibitors on Sarcopenia in Hemodialysis Patients
NCT04059913	PHASE4	COMPLETED	Evaluate the Efficacy and Safety of Multiple Roxadustat Dosing Regimens for the Treatment of Anemia in Dialysis Participants With Chronic Kidney Disease
NCT04454879	PHASE4	COMPLETED	Different Doses of Roxadustat Treatment for Anemia in Peritoneal Dialysis Patients
NCT04655027	PHASE4	COMPLETED	A Study to Investigate the Effect of Roxadustat Versus Recombinant Human Erythropoietin (rHuEPO) on Oral Iron Absorption in Chinese Patients With Anemia of Chronic Kidney Disease (CKD)
NCT05691257	PHASE4	UNKNOWN	Study of the Safety and Efficacy of Roxadustat in the Treatment of Heart Failure With Chronic Kidney Disease and Anemia
NCT06006949	PHASE4	UNKNOWN	Roxadustat Combined With Luspatercept Versus Luspatercept Monotherapy in the Treatment of Refractory MDS-RS
NCT06115421	PHASE4	UNKNOWN	Effect of Low Doses of Hypoxia-inducible Factor- Prolyl Hydroxylase Enzyme Inhibitor Plus Iron in the Treatment of Anemia in Dialysis-dependent Chronic Kidney Disease Patients
NCT07359027	PHASE4	COMPLETED	Study of Roxadustat’s Effect on Anemia in Patients With Diabetic Kidney Disease
NCT05970172	PHASE3	RECRUITING	A Study of Roxadustat to Treat Anemia in Children and Teenagers With Chronic Kidney Disease
NCT06772272	PHASE3	ACTIVE_NOT_RECRUITING	Effect of Perioperative Roxadustat in Elective Lumbar Interbody Fusion Surgery.
NCT01750190	PHASE3	COMPLETED	A Study of Roxadustat for the Treatment of Anemia in Participants With Chronic Kidney Disease and Not Receiving Dialysis
NCT01887600	PHASE3	COMPLETED	Roxadustat in the Treatment of Anemia in Chronic Kidney Disease Patients Not Requiring Dialysis
NCT02021318	PHASE3	COMPLETED	Roxadustat in the Treatment of Anemia in Chronic Kidney Disease (CKD) Patients, Not on Dialysis, in Comparison to Darbepoetin Alfa
NCT02052310	PHASE3	COMPLETED	Safety and Efficacy Study of Roxadustat (FG-4592) for the Treatment of Anemia in End-Stage Renal Disease (ESRD) Newly Initiated Dialysis Participants
NCT02174627	PHASE3	COMPLETED	Safety and Efficacy Study of Roxadustat to Treat Anemia in Patients With Chronic Kidney Disease (CKD), Not on Dialysis
NCT02174731	PHASE3	COMPLETED	Safety and Efficacy Study of Roxadustat to Treat Anemia in Patients With Chronic Kidney Disease, on Dialysis.
NCT02273726	PHASE3	COMPLETED	Study to Evaluate the Efficacy and Safety of Roxadustat in the Treatment of Anemia in Participants With ESRD on Stable Dialysis
NCT02278341	PHASE3	COMPLETED	Roxadustat in the Treatment of Anemia in End Stage Renal Disease (ESRD) Patients on Stable Dialysis
NCT02652806	PHASE3	COMPLETED	FG-4592 for Treatment of Anemia in Subjects With Chronic Kidney Disease
NCT02652819	PHASE3	COMPLETED	FG-4592 for Treatment of Anemia in Subjects With Chronic Kidney Disease Not on Dialysis
NCT02779764	PHASE3	COMPLETED	A Long Term Study of Intermittent Oral Dosing of ASP1517 in Hemodialysis Chronic Kidney Disease Patients With Anemia Converted From Erythropoieses Stimulating Agent (ESA) Treatment
NCT02780141	PHASE3	COMPLETED	A Study of Intermittent Oral Dosing of ASP1517 in Erythropoieses Stimulating Agent (ESA)-Naive Hemodialysis Chronic Kidney Disease Patients With Anemia
NCT02780726	PHASE3	COMPLETED	A Study of Intermittent Oral Dosing of ASP1517 in Peritoneal Dialysis Chronic Kidney Disease Patients With Anemia
NCT02952092	PHASE3	COMPLETED	A Study of Intermittent Oral Dosing of ASP1517 in Hemodialysis Chronic Kidney Disease Patients With Anemia
NCT02964936	PHASE3	COMPLETED	A Study of Intermittent Oral Dosing of ASP1517 in ESA-untreated Chronic Kidney Disease Patients With Anemia
NCT02988973	PHASE3	COMPLETED	A Study of Intermittent Oral Dosing of ASP1517 in Non-Dialysis Chronic Kidney Disease Patients With Anemia
NCT03263091	PHASE3	TERMINATED	Efficacy and Safety of Roxadustat for Treatment of Anemia in Participants With Lower Risk Myelodysplastic Syndrome With Low Red Blood Cell Transfusion Burden
NCT03303066	PHASE2/PHASE3	COMPLETED	Efficacy and Safety of FG-4592 for Treatment of Anemia in Participants With Lower Risk Myelodysplastic Syndrome (MDS)
NCT04410198	PHASE3	COMPLETED	Study of Roxadustat Conversion in Participants Receiving Stable Erythropoiesis-Stimulating Agent (ESA) or as Initial Anemia Treatment in Chronic Dialysis Participants
NCT04484857	PHASE3	COMPLETED	Study of Roxadustat Conversion in Participants Receiving Stable ESA or as Initial Anemia Treatment in Hemodialysis Participants
NCT04621331	PHASE3	WITHDRAWN	Investigating the Efficacy, Safety and PK of Roxadustat (FG-4592) for Treatment of Anemia in Pediatric Patients With CKD
NCT04925011	PHASE3	UNKNOWN	Investigating the Efficacy and Safety of Roxadustat (FG-4592) for Treatment of Anemia in Pediatric Patients With CKD
NCT05301517	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Roxadustat for the Treatment of Anemia in Participants Receiving Chemotherapy Treatment for Non-Myeloid Malignancies
NCT05810311	PHASE2	NOT_YET_RECRUITING	The Effect of Roxadustat on Renal Oxygenation in Diabetes Nephropathy
NCT06903559	PHASE1/PHASE2	RECRUITING	Roxadustat’s Effect on Heart, Nutrition, and Inflammation in Hemodialysis Patients
NCT06917950	PHASE1/PHASE2	RECRUITING	Roxadustat for Bone and Neuropsychiatric Aspects in Hemodialysis Patients
NCT00761657	PHASE2	COMPLETED	Phase 2 Study of Roxadustat in Participants With Anemia and Chronic Kidney Disease Not Requiring Dialysis
NCT01147666	PHASE2	COMPLETED	Study of Roxadustat (FG-4592) in Participants With End-Stage Renal Disease Receiving Maintenance Hemodialysis
NCT01244763	PHASE2	COMPLETED	Study of Roxadustat in Non-Dialysis Chronic Kidney Disease Participants With Anemia
NCT01414075	PHASE2	COMPLETED	Study of Roxadustat (FG-4592) to Correct Anemia in Newly Initiated Dialysis Participants Not on Erythropoiesis-Stimulating Agent Treatment

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.

5 molecules share ≥1 primary target. Top 5 by shared-target count:

Molecule	Source	Status	Shared targets
MOLIDUSTAT	ChEMBL + PubChem	Phase 2 (approved)	EGLN2
anhydrous citric acid	PubChem	Approved	EGLN2
ascorbic acid	PubChem	Approved	EGLN2
Malic Acid	PubChem	Approved	EGLN2
Oxygen	PubChem	Approved	EGLN2