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Atlas / Drug / Amiloride

Amiloride

drug
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Also known as AmiclaranAmiloridaHydro-rideSID11110775SID11113372SID26751628SID26751629SID90341609SID104171108SID49645530SID124879259SID124879263SID170465124SID144203631AMILORIDE HYDROCHLORIDE

Summary

Amiloride (CHEMBL945) is an approved small-molecule sodium channel blocker (ATC C03DB01) targeting GABRA6, TRPA1, and TRPC6; indicated across 10 conditions including cardiovascular disorder and hypertensive disorder.

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: C03DB01
  • Targets: 13 (GABRA6, TRPA1, TRPC6…)
  • Indications: 10 conditions
  • Clinical trials: 42
  • Chemistry: 229.63 Da · C6H8ClN7O

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL945
NameAmiloride
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID16231
ChEBICHEBI:2639
ATCC03DB01
Molecular formulaC6H8ClN7O
Molecular weight229.63
InChIKeyXSDQTOBWRPYKKA-UHFFFAOYSA-N

SMILES: C1(=C(N=C(C(=N1)Cl)N)N)C(=O)N=C(N)N

IUPAC name: 3,5-diamino-6-chloro-N-(diaminomethylidene)pyrazine-2-carboxamide

ChEBI definition: A member of the class of pyrazines resulting from the formal monoacylation of guanidine with the carboxy group of 3,5-diamino-6-chloropyrazine-2-carboxylic acid.

Pharmacological roles (ChEBI): sodium channel blocker, diuretic.

Also known as: Amiclaran, Amilorida, Amiloride, Hydro-ride, amiloride, SID11110775, SID11113372, SID26751628, SID26751629, SID90341609, SID104171108, SID49645530

Parent form; salt/anhydrous children: CHEMBL540851, CHEMBL1201085, CHEMBL1398126

Patent coverage: 17,515 distinct patent families (63,705 SureChEMBL compound mentions), from 3 matched compound structure(s). 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).

GeneTargetActionpAffinityCancer dependencyUniProt
GABRA6GABAA receptor α6 subunitAntagonist0.1%Q16445
TRPA1TRPA1Inhibition3.30.1%O75762
TRPC6TRPC6Antagonist3.90.2%Q9Y210
TRPC7TRPC7Q9HCX4
PKD2L1TRPP23.80%Q9P0L9
TRPV2TRPV21.4%Q9Y5S1
ASIC1ASIC14.682.6%P78348
ASIC2ASIC24.60.1%Q16515
ASIC3ASIC34.80%Q9UHC3
ENaCαβγ7
SLC9A1Sodium/hydrogen exchanger 1Inhibition60.2%P19634
SLC9A2Sodium/hydrogen exchanger 2Inhibition7.10.1%Q9UBY0
SLC9A3Sodium/hydrogen exchanger 3Inhibition42.2%P48764
SLC9A5Sodium/hydrogen exchanger 5Inhibition4.680.2%Q14940

Broader ChEMBL bioactivity targets: 33 (assay-derived). Sample: Urokinase-type plasminogen activator, Lysine-specific demethylase 4E, Prelamin-A/C, RecQ-like DNA helicase BLM, 15-hydroxyprostaglandin dehydrogenase [NAD(+)], Solute carrier family 22 member 2, Epithelial sodium channel subunit alpha, 5-hydroxytryptamine receptor 2B, Amine oxidase [flavin-containing] A, Thyrotropin receptor.

Bioactivity

ChEMBL activities: 32 potent at pChembl ≥ 5 of 67 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
LMNA6.15Potency707.9nMCHEMBL_ACT_3654294
SCNN1A6.11IC50776nMCHEMBL_ACT_1739351
P504826Ki1000nMCHEMBL_ACT_16889003
P264316Ki1000nMCHEMBL_ACT_16889004
P264316Ki1000nMCHEMBL_ACT_16895831
P504826Ki1000nMCHEMBL_ACT_16895846
P264316IC501000nMCHEMBL_ACT_18715250
P504826IC501000nMCHEMBL_ACT_18715270
P264315.68IC502080nMCHEMBL_ACT_25906581
P068695.64Ki2313nMCHEMBL_ACT_18556916
P068695.64IC502300nMCHEMBL_ACT_19288607
PLAU5.62IC502400nMCHEMBL_ACT_19288605
PLAU5.62IC502400nMCHEMBL_ACT_19288637
PLAU5.61Ki2433nMCHEMBL_ACT_18556812
PLAU5.6Ki2512nMCHEMBL_ACT_2651724
ADRA1A5.57AC502693nMCHEMBL_ACT_25137812
ADORA2A5.48Ki3280nMCHEMBL_ACT_523444
MAOA5.41IC503909nMCHEMBL_ACT_7637611
OPRM15.4AC504000nMCHEMBL_ACT_25146805
MAOA5.36AC504409nMCHEMBL_ACT_25159477
ASIC35.36IC504400nMCHEMBL_ACT_2521926
Q9R0W25.33Ki4700nMCHEMBL_ACT_11003117
FTO5.32IC504740nMCHEMBL_ACT_24989153
HSD17B105.3Potency5012nMCHEMBL_ACT_4873559
MAOA5.28AC505240nMCHEMBL_ACT_25160667
HTR2B5.25AC505633nMCHEMBL_ACT_25164053
PLAU5.16IC507000nMCHEMBL_ACT_10844172
Q630895.16Ki6900nMCHEMBL_ACT_11003221
PLAU5.16IC507000nMCHEMBL_ACT_1109566
PLAU5.16Ki7000nMCHEMBL_ACT_18556974

Target pathways

Aggregated over 13 target gene(s): GABRA6, TRPA1, TRPC6, TRPC7, PKD2L1, TRPV2, ASIC1, ASIC2, ASIC3, SLC9A1, SLC9A2, SLC9A3, SLC9A5.

Top Reactome pathways

16 total, by targets touching each:

PathwayTargetsGenes
Transport of small molecules7ASIC1, ASIC2, ASIC3, SLC9A1, SLC9A2, SLC9A3, SLC9A5
TRP channels4TRPA1, TRPC6, TRPC7, TRPV2
R-HSA-4253934SLC9A1, SLC9A2, SLC9A3, SLC9A5
SLC-mediated transmembrane transport4SLC9A1, SLC9A2, SLC9A3, SLC9A5
Sodium/Proton exchangers4SLC9A1, SLC9A2, SLC9A3, SLC9A5
Stimuli-sensing channels3ASIC1, ASIC2, ASIC3
Ion channel transport3ASIC1, ASIC2, ASIC3
Effects of PIP2 hydrolysis2TRPC6, TRPC7
Elevation of cytosolic Ca2+ levels2TRPC6, TRPC7
Role of second messengers in netrin-1 signaling2TRPC6, TRPC7
Metabolism1SLC9A1
Glycosaminoglycan metabolism1SLC9A1
Hyaluronan metabolism1SLC9A1
Hyaluronan degradation1SLC9A1
Metabolism of carbohydrates and carbohydrate derivatives1SLC9A1
GABA receptor activation1GABRA6

Dominant GO biological processes

GO termTargets
monoatomic ion transport13
monoatomic ion transmembrane transport9
monoatomic cation transport9
transmembrane transport8
sodium ion transmembrane transport7
sodium ion transport7
calcium ion transmembrane transport6
calcium ion transport6
potassium ion transmembrane transport5
sensory perception of sour taste4
response to acidic pH4
regulation of pH4
regulation of intracellular pH4
sodium ion import across plasma membrane4
proton transmembrane transport4

Indications & clinical

Indications

10 indications (1 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).

IndicationTrial phaseMONDOEFO
cardiovascular disorder4MONDO:0004995EFO:0000319
hypertensive disorder3MONDO:0005044EFO:0000537
coronary artery disorder2MONDO:0005010EFO:0001645
optic neuritis2MONDO:0005885EFO:0007405
primary hyperparathyroidism2MONDO:0010837EFO:0008519
secondary progressive multiple sclerosis2MONDO:0000450EFO:0008522
demyelinating disease2MONDO:0002562HP:0011096
migraine with aura2MONDO:0005475MONDO:0005475
cystic fibrosis1MONDO:0009061MONDO:0009061
attention deficit-hyperactivity disorder0MONDO:0007743EFO:0003888

Clinical trials

Total trials: 42.

Phase distribution

PhaseTrials
Not specified11
PHASE410
PHASE28
PHASE2/PHASE34
PHASE33
PHASE13
EARLY_PHASE13

Top trials by phase / activity

NCTPhaseStatusTitle
NCT01308983PHASE4UNKNOWNStudy of Amiloride on Vascular Phenotypes in Young Adults With Prehypertension
NCT01388088PHASE4COMPLETEDThe Effect of Amiloride and Spironolactone in Patients With Hypertension
NCT02122731PHASE4COMPLETEDAmiloride for Resistant Hypertension
NCT02351973PHASE4UNKNOWNComparison of Single and Combination Diuretics in Low-Renin Hypertension
NCT02522650PHASE4UNKNOWNA Crossover Pilot Study of the Effect of Amiloride on Proteinuria
NCT02832973PHASE4COMPLETEDSequential Nephron Blockade vs. Dual Blockade Renin-angiotensin System + Bisoprolol in Resistant Arterial Hypertension
NCT02847338PHASE4COMPLETEDComparison of Optimal Hypertension Regimens
NCT02875886PHASE4COMPLETEDDD-study: Diet or Diuretics for Salt-sensitivity in Chronic Kidney Disease
NCT03170336PHASE4COMPLETEDA New Application of Amiloride in the Treatment of Patient With Chronic Kidney Disease In Reducing Urinary PROtein
NCT04331691PHASE4COMPLETEDComparison of Spironolactone and Amiloride on Home Blood Pressure in Resistant Hypertension
NCT01228214PHASE2/PHASE3UNKNOWNNovel Treatment for Coronary Artery Disease
NCT01231165PHASE2/PHASE3COMPLETEDTreatment of Coronary Heart Disease With Amiloride
NCT02525796PHASE2/PHASE3COMPLETEDEvaluating Alternative Medical Therapies in Primary Hyperparathyroidism
NCT03837626PHASE2/PHASE3COMPLETEDENAC Blockade and Arterial Stiffness
NCT03928145PHASE3UNKNOWNEfficacy of Chlorthalidone and Hydrochlorothiazide Combined With Amiloride on Blood Pressure in Primary Hypertension.
NCT05079789PHASE3TERMINATEDAmiloride in Nephrotic Syndrome
NCT06416735PHASE3COMPLETEDNatriuretic Effect of Amiloride in Relation to the Alpha Adducin Gene (ADD-AMI) RS4961 Variant
NCT04063540PHASE2RECRUITINGAcid-Sensing Ion Channel and Migraine Disease Proof of Concept Study on the Efficacy of Amiloride in the Prophylaxis of Migraine Aura
NCT06224673PHASE2NOT_YET_RECRUITINGARX788 for Treating Patients With HER2-low Locally Advanced Unresectable or Metastatic Breast Cancer
NCT06923709PHASE2RECRUITINGBeneficial Effect of Amiloride on Progression of Chronic Kidney Disease
NCT00394394PHASE2COMPLETEDAntihypertensive Effectiveness of the Associations of Hydrochlorothiazide and Amiloride and Hydrochlorothiazide and Enalapril
NCT01802489PHASE2COMPLETEDAmiloride Clinical Trial In Optic Neuritis
NCT01879527PHASE2UNKNOWNAmiloride Hydrochlorothiazide as Treatment of Acute Inflammation of the Optic Nerve
NCT01910259PHASE2COMPLETEDMS-SMART: Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial
NCT02497300PHASE2COMPLETEDVascular Effects of Mineralocorticoid Receptor Antagonism in Kidney Disease
NCT05753059PHASE1RECRUITINGMechanisms of Diuretic Resistance in Heart Failure, Aim 2
NCT00857909PHASE1COMPLETEDThe Effect of Amiloride and Spironolactone in Healthy Persons
NCT01095133PHASE1COMPLETEDDo Acid Sensing Ion Channels Contribute to Heartburn?
NCT01733680EARLY_PHASE1TERMINATEDAmiloride Hydrochloride as an Effective Treatment for ADHD
NCT01804777EARLY_PHASE1TERMINATEDEpithelial Sodium Channel (ENaC) as a Novel Mechanism for Hypertension and Volume Expansion in Type 2 Diabetes
NCT04181008EARLY_PHASE1COMPLETEDPharmacokinetics of Amiloride Nasal Spray in Healthy Volunteers
NCT00004705Not specifiedCOMPLETEDStudy of Uridine Triphosphate (UTP) as an Aerosol Spray for Cystic Fibrosis
NCT00424801Not specifiedTERMINATEDEffects of Intensive Long-Term Vasodilation in Hypertensive Patients With Microvascular Angina Pectoris
NCT00429897Not specifiedUNKNOWNDouble Blind Crossover Comparison of Diuretics in the Young
NCT00478335Not specifiedCOMPLETEDPharmacologic Treatment of Congenital Nephrogenic Diabetes Insipidus
NCT00709137Not specifiedWITHDRAWNSpironolactone Versus Amiloride as an Add on Agent in Resistant Hypertension
NCT01055223Not specifiedCOMPLETEDFracture Risk With Thiazolidinediones
NCT01195805Not specifiedCOMPLETEDThe Effects of Amiloride and Spironolactone on Renophysiological and Cardiovascular Variables
NCT01246180Not specifiedCOMPLETEDMicrocirculation & ASICs
NCT01706887Not specifiedTERMINATEDGenetic Determinant of Blood Pressure Sensitivity to Salt Intake

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 1 clinical and 3 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

59 molecules share ≥1 primary target. Top 59 by shared-target count:

MoleculeSourceStatusShared targets
ENIPORIDEChEMBLPhase 2SLC9A1, SLC9A2, SLC9A3
CANNABINOLChEMBLPhase 3TRPA1, TRPV2
CANNABIDIVARINChEMBLPhase 2TRPA1, TRPV2
CANNABIGEROLChEMBLPhase 2TRPA1, TRPV2
CARIPORIDEChEMBLPhase 2SLC9A1, SLC9A2
TETRAHYDROCANNABIVARINChEMBLPhase 2TRPA1, TRPV2
ZONIPORIDEChEMBLPhase 2SLC9A1, SLC9A2
CaffeinePubChemApprovedGABRA6, TRPA1
APALUTAMIDEChEMBL + PubChemPhase 4 (approved)GABRA6
CLONAZEPAMChEMBL + PubChemPhase 4 (approved)GABRA6
DIAZEPAMChEMBL + PubChemPhase 4 (approved)GABRA6
DICLOFENACChEMBL + PubChemPhase 4 (approved)TRPA1
DISULFIRAMChEMBL + PubChemPhase 4 (approved)TRPA1
ENZALUTAMIDEChEMBL + PubChemPhase 4 (approved)GABRA6
FLUMAZENILChEMBL + PubChemPhase 4 (approved)GABRA6
MEFENAMIC ACIDChEMBL + PubChemPhase 4 (approved)TRPA1
TENAPANORChEMBL + PubChemPhase 4 (approved)SLC9A3
BREXANOLONEChEMBLPhase 4 (approved)GABRA6
GANAXOLONEChEMBLPhase 4 (approved)GABRA6
LINDANEChEMBLPhase 4 (approved)GABRA6
LIOTHYRONINEChEMBLPhase 4 (approved)GABRA6
MENTHOLChEMBLPhase 4 (approved)TRPA1
NICOTINEChEMBLPhase 4 (approved)TRPA1
PROPOFOLChEMBLPhase 4 (approved)GABRA6
RESVERATROLChEMBL + PubChemPhase 3 (approved)TRPA1
ICILLINChEMBLPhase 3TRPA1
LEVOMENTHOLChEMBLPhase 3TRPA1
ABECARNILChEMBLPhase 2GABRA6
ALLICINChEMBLPhase 2TRPA1
BAICALEINChEMBLPhase 2GABRA6
BRETAZENILChEMBLPhase 2GABRA6
CARVACROLChEMBLPhase 2TRPA1
CHLORDANTOINChEMBLPhase 2TRPA1
CLEMIZOLEChEMBLPhase 2TRPC6
DELORAZEPAMChEMBLPhase 2GABRA6
FLAVONEChEMBLPhase 2GABRA6
FLUFENAMIC ACIDChEMBLPhase 2TRPA1
PANADIPLONChEMBLPhase 2GABRA6
PROGABIDEChEMBLPhase 2GABRA6
RG6341ChEMBLPhase 2TRPA1
RIMEPORIDEChEMBLPhase 2SLC9A1
SABIPORIDEChEMBLPhase 2SLC9A1
SALIRASIBChEMBLPhase 2TRPA1
SANGUINARIUMChEMBLPhase 2TRPA1
THYMOLChEMBLPhase 2TRPA1
.gamma.-aminobutyric acidPubChemApprovedGABRA6
AcetaldehydePubChemApprovedTRPA1
alfaxalonePubChemApprovedGABRA6
AspirinPubChemApprovedASIC3
camphor (synthetic)PubChemApprovedTRPA1
CannabidiolPubChemApprovedTRPV2
CiprofloxacinPubChemApprovedGABRA6
dronabinolPubChemApprovedTRPA1
EugenolPubChemApprovedTRPA1
FipronilPubChemApprovedGABRA6
menthol, unspecified formPubChemApprovedTRPA1
PhenytoinPubChemApprovedGABRA6
Propylene GlycolPubChemApprovedTRPA1
valproatePubChemApprovedGABRA6

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot