FUROSEMIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H11ClN2O5S
Molecular Weight	330.744
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NS(=O)(=O)C1=C(Cl)C=C(NCC2=CC=CO2)C(=C1)C(O)=O

InChI

InChIKey=ZZUFCTLCJUWOSV-UHFFFAOYSA-N

InChI=1S/C12H11ClN2O5S/c13-9-5-10(15-6-7-2-1-3-20-7)8(12(16)17)4-11(9)21(14,18)19/h1-5,15H,6H2,(H,16,17)(H2,14,18,19)

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00695
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/pro/furosemide.html

Furosemide, a sulfonamide-type loop diuretic structurally related to bumetanide, is used to manage hypertension and edema associated with congestive heart failure, cirrhosis, and renal disease, including the nephrotic syndrome. Furosemide inhibits water reabsorption in the nephron by blocking the sodium-potassium-chloride cotransporter (NKCC2) in the thick ascending limb of the loop of Henle. This is achieved through competitive inhibition at the chloride binding site on the cotransporter, thus preventing the transport of sodium from the lumen of the loop of Henle into the basolateral interstitium. Consequently, the lumen becomes more hypertonic while the interstitium becomes less hypertonic, which in turn diminishes the osmotic gradient for water reabsorption throughout the nephron. Because the thick ascending limb is responsible for 25% of sodium reabsorption in the nephron, furosemide is a very potent diuretic. Furosemide is sold under the brand name Lasix among others.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Sodium-(potassium)-chloride cotransporter 2 15 Target ID: CHEMBL1874 Sources: http://www.drugbank.ca/drugs/DB00695	Inhibitor 8504
Glucose-6-phosphate 1-dehydrogenase 12 Target ID: P05370 Gene ID: 24377.0 Gene Symbol: G6pdx Target Organism: Rattus norvegicus (Rat) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26758606	Inhibitor 8504	0.13 mM [IC50]
6-phosphogluconate dehydrogenase, decarboxylating 29 Target ID: P85968 Gene ID: 1.00360176E8 Gene Symbol: Pgd Target Organism: Rattus norvegicus (Rat) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26758606	Inhibitor 8504	0.14 mM [IC50]
Glutathione reductase 11 Target ID: CHEMBL3286088 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26758606	Inhibitor 8504	0.08 mM [IC50]
Carbonic anhydrase I 62 Target ID: CHEMBL261 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10713865	Inhibitor 8504
Carbonic anhydrase XIV 22 Target ID: CHEMBL3510 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19119014	Inhibitor 8504	52.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Edema 23 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/016273s068lbl.pdf	Primary		Approved 8583	LASIX Approved Use Edema Furosemide is indicated in adults and pediatric patients for the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and renal disease, including the nephrotic syndrome. Furosemide is particularly useful when an agent with greater diuretic potential is desired. Hypertension Oral Furosemide may be used in adults for the treatment of hypertension alone or in combination with other antihypertensive agents. Launch Date 1966
Hypertension 575 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/016273s068lbl.pdf	Primary		Approved 8583	LASIX Approved Use Edema Furosemide is indicated in adults and pediatric patients for the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and renal disease, including the nephrotic syndrome. Furosemide is particularly useful when an agent with greater diuretic potential is desired. Hypertension Oral Furosemide may be used in adults for the treatment of hypertension alone or in combination with other antihypertensive agents. Launch Date 1966

C_max

Value	Dose	Co-administered	Analyte	Population
1315.34 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12854359	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		FUROSEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
3014.77 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12854359	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		FUROSEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12854359	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		FUROSEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
3.2% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/016273s061lbl.pdf			FUROSEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP1A 26 OAT1 395 OAT3 391 UGT1A1 479 UGT1A3 470 UGT1A6 343 UGT1A7 249 UGT1A9 423 UGT1A10 331 UGT2B7 456 MRP4 91 BCRP 697 MRP1 113 MRP2 252 P-gp 2052

Drug as victim

Target	Modality	Activity	Clinical evidence
UGT1A9 423	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/18541222/ Page: 1.0	major
OAT1 395	substrate 4014 Sources: https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1002/cpt.406#page=9 Page: 9.0	major	yes (co-administration study) Comment: probe drug substrate for renal transporters OAT1 and OAT3; clinical investigation of a probe drug cocktail containing substrates of key drug transporters (digoxin, furosemide, metformin and rosuvastatin) Sources: https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1002/cpt.406#page=9 Page: 9.0
OAT3 391	substrate 4014 Sources: https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1002/cpt.406#page=9 Page: 9.0	major	yes (co-administration study) Comment: probe drug substrate for renal transporters OAT1 and OAT3; clinical investigation of a probe drug cocktail containing substrates of key drug transporters (digoxin, furosemide, metformin and rosuvastatin) Sources: https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1002/cpt.406#page=9 Page: 9.0
MRP1 113	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11948555/ Page: 6.0	no
MRP2 252	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11948555/ Page: 6.0	no
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11948555/ Page: 6.0	no
BCRP 697	substrate 4014 Sources: https://jasn.asnjournals.org/content/jnephrol/18/1/37.full.pdf?with-ds=yes#page=6 Page: 6.0	yes
MRP4 91	substrate 4014 Sources: https://jasn.asnjournals.org/content/jnephrol/18/1/37.full.pdf?with-ds=yes#page=1 Page: 1.0	yes
UGT1A1 479	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/18541222/ Page: 1.0	yes
UGT1A10 331	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/18541222/ Page: 1.0	yes
UGT1A3 470	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/18541222/ Page: 1.0	yes
UGT1A6 343	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/18541222/ Page: 1.0	yes
UGT1A7 249	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/18541222/ Page: 1.0	yes
UGT2B7 456	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/18541222/ Page: 1.0	yes
CYP1A 26	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19126296/ Page: 1.0	yes	yes (co-administration study) Comment: The time-averaged non-renal clearance (CLNR) of furosemide tended to be faster (but not significantly so) among smokers (3-methylcholanthrene (3-MC) type; a main inducer of CYP1A1/2 Sources: https://pubmed.ncbi.nlm.nih.gov/19126296/ Page: 1.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/15950494/ Page: 8.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:47426	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:47426
ChemicalBook	CB2445739	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2445739
eMolecules	538364	https://www.emolecules.com/cgi-bin/more?vid=538364
MolPort	MolPort-001-641-065	https://www.molport.com/shop/molecule-link/MolPort-001-641-065
Selleck Chemicals	Furosemide(Lasix)	http://www.selleckchem.com/products/Furosemide(Lasix).html
ZINC	ZINC000000035804	http://zinc15.docking.org/substances/ZINC000000035804

PubMed

Title	Date	PubMed
Nephrocalcinosis in full-term infants receiving furosemide treatment for congestive heart failure: a study of the incidence and 2-year follow up.	1999 Aug	10445348
[Hypokalemic paralysis in furosemide therapy and simultaneous laxative abuse].	1999 Jul 15	10437370
Nephrotic syndrome and acute interstitial nephritis associated with the use of diclofenac.	1999 Jul 9	10444806
Oxalate nephrocalcinosis in renal tubular dysgenesis.	1999 Nov	10671031
Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta.	2000 Feb 11	10660625
Release of furosemide from multiple-unit and single-unit preparations containing different viscosity grades of sodium alginate.	2001	11247279
Diuretic-enhanced gadolinium excretory MR urography: comparison of conventional gradient-echo sequences and echo-planar imaging.	2001	11194911
Maxi K+ channels co-localised with CFTR in the apical membrane of an exocrine gland acinus: possible involvement in secretion.	2001 Apr	11374055
Pressure-independent enhancement of cardiac hypertrophy in natriuretic peptide receptor A-deficient mice.	2001 Apr	11306601
Systemic sclerosis (scleroderma). A case of recovery of cardiomyopathy after vitamin E treatment.	2001 Apr	11292956
Chronic tubulointerstitial nephritis and distal renal tubular acidosis in a patient with frusemide abuse.	2001 Apr	11274294
Alternatively spliced isoform of apical Na(+)-K(+)-Cl(-) cotransporter gene encodes a furosemide-sensitive Na(+)-Cl(-)cotransporter.	2001 Apr	11249848
Distinguishing cochlear pathophysiology in 4-aminopyridine and furosemide treated ears using a nonlinear systems identification technique.	2001 Feb	11248972
Renal interstitial atp responses to changes in arterial pressure during alterations in tubuloglomerular feedback activity.	2001 Feb	11230369
Brown Norway chromosome 13 confers protection from high salt to consomic Dahl S rat.	2001 Feb	11230318
Effect of furosemide on renal excretion of oxypurinol and purine bases.	2001 Feb	11229436
Hyponatremia and sensorineural hearing loss in preterm infants.	2001 Feb	11223652
Mechanisms of chloride transport in thymic lymphocytes.	2001 Feb	11208607
Congestive heart failure associated with myxomatous degeneration of the left atrioventricular valve in a parakeet.	2001 Feb 1	11201563
Activation of Na(+), K(+), Cl(-)-cotransport mediates intracellular Ca(2+) increase and apoptosis induced by Pinacidil in HepG2 human hepatoblastoma cells.	2001 Feb 23	11181077
Self-retaining aural speculum: a valuable aid to middle-ear surgery.	2001 Jan	11233622
10% hydroxyethyl starch for plasma expansion in the treatment of severe ovarian hyperstimulation syndrome. A case report.	2001 Jan	11209636
Acute congestive heart failure associated with a limited form of systemic sclerosis and primary biliary cirrhosis.	2001 Jan	11201376
Renal cortical scintigraphy and diuresis renography in infants and children.	2001 Jan	11197988
Prehospital management of rapid atrial fibrillation: recommendations for treatment protocols.	2001 Jan	11146008
Furosemide stimulates macula densa cyclooxygenase-2 expression in rats.	2001 Jan	11135058
Renal follow up of premature infants with and without perinatal indomethacin exposure.	2001 Jan	11124920
[Rhabdomyolysis as a rare complication of theophylline poisoning].	2001 Jan 15	11210488
[Life threatening hypercalcemia in a young man with ALL].	2001 Jan 5	11200666
Pamidronate and calcitonin as therapy of acute cancer-related hypercalcemia in children.	2001 Jan-Feb	11225473
The effects of enalapril-digoxin-diuretic combination therapy on nutritional and anthropometric indices in chronic congestive heart failure: preliminary findings in cardiac cachexia.	2001 Jun	11378008
Urolithiasis in the low birth weight infant: the role and efficacy of extracorporeal shock wave lithotripsy.	2001 Jun	11371971
Angiotensin converting enzyme inhibition worsens the excretory phase of diuretic renography for obstructive hydronephrosis.	2001 Jun	11371966
Dynamic characteristics and underlying mechanisms of renal blood flow autoregulation in the conscious dog.	2001 Jun	11352846
Humoral hypercalcemia of malignancy in squamous cell carcinoma of the skin: parathyroid hormone--related protein as a cause.	2001 Mar	11284521
Estimation of the probability for exceeding a threshold concentration of furosemide at various intervals after intravenous administration in horses.	2001 Mar	11277194
Effect of furosemide on basal lamina anionic sites in guinea pig labyrinth.	2001 Mar	11269776
Optical imaging reveals cation--Cl(-) cotransporter-mediated transient rapid decrease in intracellular Cl(-) concentration induced by oxygen--glucose deprivation in rat neocortical slices.	2001 Mar	11248366
Aggressive diuresis for severe heart failure in the elderly.	2001 Mar	11243961
Intraplatelet calcium levels in patients with acute renal failure before and after the administration of loop diuretics.	2001 Mar	11239030
Homogeneous enzyme immunoassay for triiodothyronine in serum.	2001 Mar	11238313
Role of diuretics in the preservation of residual renal function in patients on continuous ambulatory peritoneal dialysis.	2001 Mar	11231370
Effects of albumin/furosemide mixtures on responses to furosemide in hypoalbuminemic patients.	2001 May	11316860
Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney.	2001 May	11306713

Patents

Sample Use Guides

In Vivo Use Guide

The usual initial dose of LASIX is 20 to 80 mg given as a single dose. Ordinarily a prompt diuresis ensues. If needed, the same dose can be administered 6 to 8 hours later or the dose may be increased. The dose may be raised by 20 or 40 mg and given not sooner than 6 to 8 hours after the previous dose until the desired diuretic effect has been obtained. The individually determined single dose should then be given once or twice daily (eg, at 8 am and 2 pm). The dose of LASIX may be carefully titrated up to 600 mg/day in patients with clinically severe edematous states.

Route of Administration: Oral

In Vitro Use Guide

There was a significant reduction in levels of TNF-alpha and IL-6 at a furosemide concentration of 0.5 x 10(-2) M and a reduction in IL-8 levels at 10(-2) M in human peripheral blood mononuclear cells.

Name

Type

Language

FUROSCIX

Preferred Name

English

FUROSEMIDE

Official Name

English

5-(AMINOSULFONYL)-4-CHLORO-2-((2-FURYLMETHYL)AMINO)BENZOIC ACID

Systematic Name

English

Furosemide [WHO-DD]

Common Name

English

BENZOIC ACID, 5-(AMINOSULFONYL)-4-CHLORO-2-((2-FURANYLMETHYL)AMINO)-

Common Name

English

LOGIRENE

Brand Name

English

FUROSEMIDE [IARC]

Common Name

English

FUROSEMIDE [ORANGE BOOK]

Common Name

English

FUROSEMIDE [EP MONOGRAPH]

Common Name

English

FUROSEMIDE [WHO-IP]

Common Name

English

FUROSEMIDE [VANDF]

Common Name

English

LB-502

Code

English

OEDEMEX

Common Name

English

FUROSEMIDE [JAN]

Common Name

English

FUROSEMIDUM [WHO-IP LATIN]

Common Name

English

FUROSEMIDE [USP MONOGRAPH]

Common Name

English

FRUSEMIDE

Common Name

English

FUROSEMIDE [GREEN BOOK]

Common Name

English

MARSEMIDE

Common Name

English

furosemide [INN]

Common Name

English

LASIX

Brand Name

English

MIRFAT

Brand Name

English

4-Chloro-N-furfuryl-5-sulfamoylanthranilic acid

Systematic Name

English

NSC-269420

Code

English

FUROSEMIDE [MART.]

Common Name

English

FUROSEMIDE [MI]

Common Name

English

FUROSEMIDE [HSDB]

Common Name

English

FUROSEMIDE [USAN]

Common Name

English

FUROSEMIDE [USP-RS]

Common Name

English

Classification Tree Code System Code

WHO-ESSENTIAL MEDICINES LIST

12.4