Bumetanide

Summary

Bumetanide (CHEMBL1072) is an approved small-molecule diuretic (ATC C03CA02) targeting GPR35, SLC12A1, and SLC12A2; indicated across 14 conditions including congestive heart failure and kidney disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C03CA02
• Targets: 3 (GPR35, SLC12A1, SLC12A2)
• Indications: 14 conditions
• Clinical trials: 24
• Chemistry: 364.4 Da · C17H20N2O5S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1072
Name	Bumetanide
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	2471
ChEBI	CHEBI:3213
ATC	C03CA02
Molecular formula	C17H20N2O5S
Molecular weight	364.4
InChIKey	MAEIEVLCKWDQJH-UHFFFAOYSA-N

SMILES: CCCCNC1=C(C(=CC(=C1)C(=O)O)S(=O)(=O)N)OC2=CC=CC=C2

IUPAC name: 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid

ChEBI definition: A member of the class of benzoic acids that is 4-phenoxybenzoic acid in which the hydrogens ortho to the phenoxy group are substituted by butylamino and sulfamoyl groups. Bumetanide is a diuretic, and is used for treatment of oedema associated with congestive heart failure, hepatic and renal disease.

Pharmacological roles (ChEBI): diuretic, EC 3.6.3.49 (channel-conductance-controlling ATPase) inhibitor.

Also known as: Betinex, Bumetanida, Bumetanide, Bumex, Burinex, Lixil, PF-1593, PF1593, RO-106338, S-95008., S95008., SID11110843

Patent coverage: 5,785 distinct patent families (22,087 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 22,028 (100%) 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
GPR35	GPR35	Agonist	5.54	0.2%	Q9HC97
SLC12A1	Kidney-specific Na-K-Cl symporter	Inhibition	6.48	0.6%	Q13621
SLC12A2	Basolateral Na-K-Cl symporter	Inhibition	5.6	0.1%	P55011

Broader ChEMBL bioactivity targets: 15 (assay-derived). Sample: Lysine-specific demethylase 4E, Ubiquitin carboxyl-terminal hydrolase 2, Prelamin-A/C, RecQ-like DNA helicase BLM, Ferritin light chain, 15-hydroxyprostaglandin dehydrogenase [NAD(+)], Solute carrier family 12 member 2, Solute carrier family 22 member 6, Thyrotropin receptor, Carbonic anhydrase 2.

Bioactivity

ChEMBL activities: 15 potent at pChembl ≥ 5 of 36 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HIF1A	6.1	Potency	794.3	nM	CHEMBL_ACT_4128783
HIF1A	6.1	Potency	794.3	nM	CHEMBL_ACT_4518576
SLC12A2	5.81	IC50	1540	nM	CHEMBL_ACT_24996400
HIF1A	5.8	Potency	1585	nM	CHEMBL_ACT_4129563
HIF1A	5.8	Potency	1585	nM	CHEMBL_ACT_4518599
NPSR1	5.5	Potency	3162	nM	CHEMBL_ACT_4920908
HIF1A	5.4	Potency	3981	nM	CHEMBL_ACT_4117758
HIF1A	5.4	Potency	3981	nM	CHEMBL_ACT_4519809
O35956	5.26	Ki	5500	nM	CHEMBL_ACT_11003174
LMNA	5.25	Potency	5623	nM	CHEMBL_ACT_3649779
TSHR	5.2	Potency	6310	nM	CHEMBL_ACT_3923643
TSHR	5.2	Potency	6310	nM	CHEMBL_ACT_4618772
USP2	5.2	Potency	6310	nM	CHEMBL_ACT_4727649
CA2	5.16	Ki	6980	nM	CHEMBL_ACT_26047521
LMNA	5.05	Potency	8912	nM	CHEMBL_ACT_3636548

Target pathways

Aggregated over 3 target gene(s): GPR35, SLC12A1, SLC12A2.

Top Reactome pathways

9 total, by targets touching each:

Pathway	Targets	Genes
Transport of small molecules	2	SLC12A1, SLC12A2
R-HSA-425393	2	SLC12A1, SLC12A2
SLC-mediated transmembrane transport	2	SLC12A1, SLC12A2
Cation-coupled Chloride cotransporters	2	SLC12A1, SLC12A2
Disease	1	SLC12A1
Class A/1 (Rhodopsin-like receptors)	1	GPR35
SLC transporter disorders	1	SLC12A1
Defective SLC12A1 causes Bartter syndrome 1 (BS1)	1	SLC12A1
Disorders of transmembrane transporters	1	SLC12A1

Dominant GO biological processes

GO term	Targets
monoatomic ion transport	2
cell volume homeostasis	2
sodium ion transmembrane transport	2
chloride ion homeostasis	2
potassium ion homeostasis	2
sodium ion homeostasis	2
transepithelial ammonium transport	2
chloride transmembrane transport	2
potassium ion import across plasma membrane	2
potassium ion transport	2
sodium ion transport	2
transmembrane transport	2
potassium ion transmembrane transport	2
monocyte chemotaxis	1
response to ischemia	1

Indications & clinical

Indications

14 indications (5 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
congestive heart failure	4	MONDO:0005009	EFO:0000373
kidney disorder	4	MONDO:0005240	EFO:0003086
nephrotic syndrome	4	MONDO:0005377	EFO:0004255
heart failure	4	MONDO:0005252	EFO:0003144
cardiovascular disorder	4	MONDO:0004995	EFO:0000319
autism	3	MONDO:0005260	EFO:0003758
autism spectrum disorder	3	MONDO:0005258	EFO:0003756
chronic kidney disease	2	MONDO:0005300	EFO:0003884
hypokalemic periodic paralysis	2	MONDO:0008223	MONDO:0008223
Down syndrome	2	MONDO:0008608	EFO:0001064
Alzheimer disease	2	MONDO:0004975	MONDO:0004975
visual epilepsy	1	MONDO:0001386	HP:0001250
hepatocellular carcinoma	1	MONDO:0007256	EFO:0000182
type 2 diabetes mellitus	1	MONDO:0005148	MONDO:0005148

Clinical trials

Total trials: 24.

Phase distribution

Phase	Trials
PHASE2	8
PHASE3	6
PHASE4	4
PHASE1	3
PHASE1/PHASE2	2
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06218199	PHASE4	RECRUITING	Diuretics vs. Afterload Reduction for Treatment of HeartLogic Alerts
NCT03709160	PHASE4	UNKNOWN	Oral dIuretics in Very Intensive Treatment, an Early Intervention in Outpatients With Heart Failure
NCT04697485	PHASE4	WITHDRAWN	Polydiuretic Therapy for Heart Failure With Preserved Ejection Fraction and Diabetes Mellitus
NCT07375212	PHASE4	WITHDRAWN	VAPorized Administration of Bumetanide for Outpatient Relief in Heart Failure
NCT04766177	PHASE3	RECRUITING	Role of Bumetanide in Treatment of Autism
NCT06941415	PHASE3	NOT_YET_RECRUITING	Bumetanide vs. Furosemide in Cirrhosis
NCT00372762	PHASE3	WITHDRAWN	Bumetanide Versus Furosemide in Heart Failure
NCT01078714	PHASE3	COMPLETED	Efficiency of Bumetanide in Autistic Children
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT03107416	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Delivering a Diuretic Into the Liver Artery Followed by Plugging up the Artery to Starve Out Liver Cancer Cells
NCT06052163	PHASE2	RECRUITING	Bumetanide in Patients With Alzheimer’s Disease
NCT06465823	PHASE2	RECRUITING	Efficacy of Bumetanide to Improve Cognitive Functions in Down Syndrome
NCT01434225	PHASE1/PHASE2	COMPLETED	NEMO1:NEonatal Seizure Using Medication Off-patent
NCT02582476	PHASE2	TERMINATED	Bumetanide in Hypokalaemic Periodic Paralysis
NCT02947880	PHASE2	WITHDRAWN	Evaluation of the Efficiency of Treatment by BUMETANIDE on Autistic Children With a Known Ethiology
NCT03156153	PHASE2	COMPLETED	A Study of Bumetanide for the Treatment of Autism Spectrum Disorders
NCT03923933	PHASE2	COMPLETED	Chlortalidone and Bumetanide in Advanced Chronic Kidney Disease: HEBE-CKD Trial
NCT06036914	PHASE2	COMPLETED	A Study of Ultra High Dose Diuretics to Treat Heart Failure
NCT07005414	PHASE2	COMPLETED	Efficacy of Bumetanide in Children With Autism Spectrum Disorder Guided by Peripheral Blood Biomarkers and Machine Learning Models
NCT05323487	PHASE1	RECRUITING	Mechanisms of Diuretic Resistance in Heart Failure, Aim 1
NCT00830531	PHASE1	COMPLETED	Pilot Study of Bumetanide for Newborn Seizures
NCT00930865	PHASE1	COMPLETED	Study to Evaluate the Potential Pharmacokinetic Interaction and Pharmacodynamic Effects on Renal Parameters of Bumetanide (1mg) and Dapagliflozin (10 mg) When Co-administered in Healthy Subjects
NCT02593526	Not specified	TERMINATED	Diuretic/Cool Dialysate Trial

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 5 clinical and 14 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.

28 molecules share ≥1 primary target. Top 28 by shared-target count:

Molecule	Source	Status	Shared targets
FUROSEMIDE	ChEMBL + PubChem	Phase 4 (approved)	GPR35, SLC12A1, SLC12A2
CROMOLYN	ChEMBL + PubChem	Phase 4 (approved)	GPR35
AMLEXANOX	ChEMBL	Phase 4 (approved)	GPR35
APREPITANT	ChEMBL	Phase 4 (approved)	GPR35
CINACALCET	ChEMBL	Phase 4 (approved)	GPR35
DICUMAROL	ChEMBL	Phase 4 (approved)	GPR35
EMETINE	ChEMBL	Phase 4 (approved)	GPR35
ENTACAPONE	ChEMBL	Phase 4 (approved)	GPR35
FLUOXETINE	ChEMBL	Phase 4 (approved)	GPR35
LODOXAMIDE	ChEMBL	Phase 4 (approved)	GPR35
LOPERAMIDE	ChEMBL	Phase 4 (approved)	GPR35
NEFAZODONE	ChEMBL	Phase 4 (approved)	GPR35
PERPHENAZINE	ChEMBL	Phase 4 (approved)	GPR35
PIMAVANSERIN	ChEMBL	Phase 4 (approved)	GPR35
TOLCAPONE	ChEMBL	Phase 4 (approved)	GPR35
VORAPAXAR	ChEMBL	Phase 4 (approved)	GPR35
QUERCETIN	ChEMBL + PubChem	Phase 3 (approved)	GPR35
2,4-DINITROPHENOL	ChEMBL	Phase 2	GPR35
BAICALEIN	ChEMBL	Phase 2	GPR35
BUFROLIN	ChEMBL	Phase 2	GPR35
BX 471 FREE BASE	ChEMBL	Phase 2	GPR35
ELLAGIC ACID	ChEMBL	Phase 2	GPR35
FORETINIB	ChEMBL	Phase 2	GPR35
LUTEOLIN	ChEMBL	Phase 2	GPR35
NIFLUMIC ACID	ChEMBL	Phase 2	GPR35
NIGULDIPINE	ChEMBL	Phase 2	GPR35
NITECAPONE	ChEMBL	Phase 2	GPR35
ZAPRINAST	ChEMBL	Phase 2	GPR35