Febuxostat

Summary

Febuxostat (CHEMBL1164729) is an approved small-molecule EC 1.17.3.2 (xanthine oxidase) inhibitor (ATC M04AA03) targeting XDH; indicated across 9 conditions including gout and cardiovascular disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: M04AA03
• Targets: 1 (XDH)
• Indications: 9 conditions
• Clinical trials: 85
• Chemistry: 316.4 Da · C16H16N2O3S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1164729
Name	Febuxostat
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	134018
ChEBI	CHEBI:31596
ATC	M04AA03
Molecular formula	C16H16N2O3S
Molecular weight	316.4
InChIKey	BQSJTQLCZDPROO-UHFFFAOYSA-N

SMILES: CC1=C(SC(=N1)C2=CC(=C(C=C2)OCC(C)C)C#N)C(=O)O

IUPAC name: 2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methyl-1,3-thiazole-5-carboxylic acid

ChEBI definition: A 1,3-thiazolemonocarboxylic acid that is 4-methyl-1,3-thiazole-5-carboxylic acid which is substituted by a 3-cyano-4-(2-methylpropoxy)phenyl group at position 2. It is an orally-active, potent, and selective xanthine oxidase inhibitor used for the treatment of chronic hyperuricaemia in patients with gout.

Pharmacological roles (ChEBI): EC 1.17.3.2 (xanthine oxidase) inhibitor.

Also known as: Adenuric, Febuxostat, Febuxostat krka, Febuxostat mylan, NSC-758874, TMX-67, Uloric, FEBUXOSTAT, SID124893781, febuxostat, SID170465220, SID144206555

Patent coverage: 2,007 distinct patent families (3,499 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 3,469 (99%) 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
XDH	xanthine dehydrogenase	Inhibition	7.52	0%	P47989

Broader ChEMBL bioactivity targets: 12 (assay-derived). Sample: Xanthine dehydrogenase/oxidase, ATP-binding cassette sub-family C member 4, Protein deacetylase HDAC6, Xanthine dehydrogenase/oxidase, Progesterone receptor, RISC-loading complex subunit TARBP2, Muscarinic acetylcholine receptor M1, 3’,5’-cyclic-AMP phosphodiesterase 4A, Xanthine dehydrogenase/oxidase, Flavin reductase (NADPH).

Bioactivity

ChEMBL activities: 46 potent at pChembl ≥ 5 of 51 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
XDH	10	Ki	0.1	nM	CHEMBL_ACT_18252132
XDH	10	Ki	0.1	nM	CHEMBL_ACT_24885795
P80457	9.92	Ki	0.12	nM	CHEMBL_ACT_15008221
XDH	9.22	Ki	0.6	nM	CHEMBL_ACT_20627773
P80457	9.22	Ki	0.6	nM	CHEMBL_ACT_25708401
P80457	9.05	Ki	0.9	nM	CHEMBL_ACT_15008220
XDH	8.9	IC50	1.26	nM	CHEMBL_ACT_13949012
P80457	8.56	IC50	2.78	nM	CHEMBL_ACT_25597661
XDH	8.54	IC50	2.92	nM	CHEMBL_ACT_24840401
P80457	8.54	IC50	2.91	nM	CHEMBL_ACT_29095998
P80457	8.52	IC50	3	nM	CHEMBL_ACT_3343844
XDH	8.51	Ki	3.1	nM	CHEMBL_ACT_20627774
P80457	8.51	Ki	3.1	nM	CHEMBL_ACT_25708402
P22985	8.4	IC50	3.98	nM	CHEMBL_ACT_13947453
P80457	8.32	IC50	4.8	nM	CHEMBL_ACT_18959263
P80457	8.28	IC50	5.2	nM	CHEMBL_ACT_18521668
XDH	8.16	IC50	6.91	nM	CHEMBL_ACT_25587743
P80457	8.15	IC50	7	nM	CHEMBL_ACT_22459266
XDH	8.1	IC50	8	nM	CHEMBL_ACT_25881171
XDH	8.1	IC50	8	nM	CHEMBL_ACT_26044618
P80457	8	IC50	10	nM	CHEMBL_ACT_15759525
P80457	8	IC50	10	nM	CHEMBL_ACT_15759540
P80457	8	IC50	10	nM	CHEMBL_ACT_18164469
P80457	8	IC50	10	nM	CHEMBL_ACT_25835400
XDH	8	IC50	10	nM	CHEMBL_ACT_29153325
XDH	7.89	IC50	13	nM	CHEMBL_ACT_18434398
P80457	7.75	IC50	18	nM	CHEMBL_ACT_19210028
P80457	7.75	IC50	18	nM	CHEMBL_ACT_23205068
P80457	7.73	IC50	18.6	nM	CHEMBL_ACT_15026710
P80457	7.72	IC50	18.9	nM	CHEMBL_ACT_22442329

Target pathways

Aggregated over 1 target gene(s): XDH.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
Purine catabolism	1	XDH
Butyrophilin (BTN) family interactions	1	XDH
Azathioprine ADME	1	XDH

Dominant GO biological processes

GO term	Targets
allantoin metabolic process	1
guanine catabolic process	1
inosine catabolic process	1
deoxyinosine catabolic process	1
adenosine catabolic process	1
deoxyadenosine catabolic process	1
deoxyguanosine catabolic process	1
AMP catabolic process	1
IMP catabolic process	1
lactation	1
hypoxanthine catabolic process	1
xanthine catabolic process	1
iron-sulfur cluster assembly	1
regulation of epithelial cell differentiation	1
obsolete amide catabolic process	1

Indications & clinical

Indications

9 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
gout	4	MONDO:0005393	EFO:0004274
cardiovascular disorder	3	MONDO:0004995	EFO:0000319
tumor lysis syndrome	3	MONDO:0043875	EFO:1001479
hypertensive disorder	2	MONDO:0005044	EFO:0000537
kidney disorder	2	MONDO:0005240	EFO:0003086
metabolic dysfunction-associated steatotic liver disease	2	MONDO:0013209	EFO:0003095
nephrolithiasis	2	MONDO:0008171	EFO:0004253

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

Clinical trials

Total trials: 85.

Phase distribution

Phase	Trials
PHASE2	23
PHASE3	19
PHASE4	17
Not specified	12
PHASE1	10
PHASE1/PHASE2	2
PHASE2/PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06622603	PHASE4	RECRUITING	the Effects of Febuxostat Dose Tapering in Gout Patients Optimally Controlled for 5 Years or More
NCT06834230	PHASE4	RECRUITING	Effect of Dotinurad in Hyperuricemia With Hypertension
NCT07369622	PHASE4	NOT_YET_RECRUITING	HLA-B*58:01-Guided Therapy for Gout: Effectiveness, Safety, and Cost-Effectiveness
NCT01112982	PHASE4	COMPLETED	An Assessment of Chronic Synovial-Based Inflammation and Its Role With Serum Urate Levels.
NCT01328769	PHASE4	COMPLETED	Febuxostat, Blood Pressure and the Intrarenal Renin-Angiotensin System (RAS)
NCT01472692	PHASE4	COMPLETED	Study of Febuxostat Effect on Blood Pressure in Patients With High Normal Blood Pressure
NCT01654276	PHASE4	COMPLETED	Effects of Hyperuricemia Reversal on Features of the Metabolic Syndrome
NCT01763996	PHASE4	COMPLETED	The Influence of Febuxostat on Coronary Artery Endothelial Dysfunction in Participants With Chronic Stable Angina
NCT02060552	PHASE4	COMPLETED	Immune Molecular and Inflammatory Cytokines Dysfunction Analysis in Gout Patients With Different Urate Levels
NCT02279342	PHASE4	TERMINATED	the Effect of Febuxostat on Coronary Plaque Volume in Patients With Chronic Stable Angina and Hyperuricemia
NCT02344602	PHASE4	COMPLETED	The Effect of Uric Acid Lowering in Type 1 Diabetes
NCT02500641	PHASE4	COMPLETED	Intensive Urate Lowering Therapy of Febuxostat Compared to Allopurinol on Cardiovascular Risk in Patients With Gout
NCT02600780	PHASE4	COMPLETED	Zurig (Febuxostat) 40mg Efficacy and Safety Trial
NCT02752633	PHASE4	COMPLETED	Effect of Allopurinol and Febuxostat on Urinary 2,8-Dihydroxyadenine Excretion
NCT03200210	PHASE4	UNKNOWN	Lowering-hyperuricemia Treatment on Cardiovascular Outcomes in Peritoneal Dialysis Patients
NCT03425708	PHASE4	UNKNOWN	Effect of Hyperuricaemia on Chronic Renal Disease
NCT03534037	PHASE4	UNKNOWN	Urate Lowering Therapies and Left Ventricular Diastolic Dysfunction
NCT05109936	PHASE3	RECRUITING	Immediate Prescription of a Hypouricemic Treatment, Febuxostat, Compared to Its Delayed Administration
NCT06414837	PHASE3	NOT_YET_RECRUITING	Clinical Trial of HR091506 Tablets in Treatment of Gout With Hyperuricemia in Adults
NCT07414394	PHASE3	RECRUITING	Tigulixostat (IBI128) vs Febuxostat in Gout
NCT00102440	PHASE3	COMPLETED	Febuxostat Versus Allopurinol Control Trial in Subjects With Gout
NCT00174915	PHASE3	COMPLETED	Phase 3, Febuxostat, Allopurinol and Placebo-Controlled Study in Gout Subjects.
NCT00175019	PHASE3	COMPLETED	Allopurinol Versus Febuxostat in Subjects Completing the Phase 3 Trials C02-009 or C02-010
NCT00430248	PHASE3	COMPLETED	Efficacy and Safety of Oral Febuxostat in Participants With Gout
NCT00821392	PHASE3	COMPLETED	Phase III Trial of Febuxostat in Korea Gout Patients
NCT01101035	PHASE3	COMPLETED	Cardiovascular Safety of Febuxostat and Allopurinol in Participants With Gout and Cardiovascular Comorbidities (CARES)
NCT01510769	PHASE3	COMPLETED	Combination Treatment Study in Subjects With Tophaceous Gout With Lesinurad and Febuxostat
NCT01724528	PHASE3	COMPLETED	Febuxostat for Tumor Lysis Syndrome Prevention in Hematologic Malignancies
NCT01736514	PHASE3	COMPLETED	A Study to Evaluate Safety and Efficacy of Oral Febuxostat in Patients With Gout
NCT01808144	PHASE3	COMPLETED	Lesinurad and Febuxostat Combination Extension Study in Gout
NCT02082769	PHASE3	COMPLETED	Safety and Efficacy of Oral Febuxostat in Subjects With Gout
NCT02139046	PHASE3	COMPLETED	Efficacy and Safety of Extended Release and Immediate Release Febuxostat in Participants With Gout
NCT02866214	PHASE2/PHASE3	COMPLETED	Effect of Febuxostat on Endothelial Dysfunction in Hemodialysis Patients.
NCT03372200	PHASE3	COMPLETED	Febuxostat-Controlled, Double-Blind, Comparative Study of FYU-981 in Hyperuricemia With or Without Gout
NCT05007392	PHASE3	COMPLETED	A Study to Evaluate Efficacy of Dotinurad and Febuxostat for the Treatment of Participants With Gout
NCT05815901	PHASE3	COMPLETED	A Therapeutic Confirmatory Study of Epaminurad Versus Febuxostat in Gout Patients
NCT06139393	PHASE3	COMPLETED	Clinical Study of HR091506 Tablets in Treatment of Gout With Hyperuricemia in Adults
NCT06995339	PHASE2	RECRUITING	Comparative Clinical and Biochemical Study Evaluating the Effectiveness of Metformin Versus Febuxostat on Gouty Obese Non-Diabetic Patients
NCT07362355	PHASE2	RECRUITING	The Efficacy and Safety of SHR4640 Tablet Combined With 40 mg Febuxostat Tablets in the Treatment of Primary Gout and Hyperuricemia
NCT07485452	PHASE2	NOT_YET_RECRUITING	Boosting Osimertinib Blood Brain Barrier Penetration

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 3 clinical and 5 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

14 molecules share ≥1 primary target. Top 14 by shared-target count:

Molecule	Source	Status	Shared targets
ALLOPURINOL	ChEMBL + PubChem	Phase 4 (approved)	XDH
INDOMETHACIN	ChEMBL	Phase 4 (approved)	XDH
THIOGUANINE	ChEMBL	Phase 4 (approved)	XDH
ADENINE	ChEMBL	Phase 3	XDH
QUERCETIN	ChEMBL	Phase 3	XDH
RUTIN	ChEMBL	Phase 3	XDH
BAICALEIN	ChEMBL	Phase 2	XDH
BROPIRIMINE	ChEMBL	Phase 2	XDH
FISETIN	ChEMBL	Phase 2	XDH
GENISTEIN	ChEMBL	Phase 2	XDH
ISOQUERCETIN	ChEMBL	Phase 2	XDH
LUTEOLIN	ChEMBL	Phase 2	XDH
OXYPURINOL	ChEMBL	Phase 2	XDH
TOPIROXOSTAT	ChEMBL	Phase 2	XDH