Indapamide

Summary

Indapamide (CHEMBL406) is an approved small-molecule antihypertensive agent (ATC C03BA11) targeting NAPEPLD; indicated across 7 conditions including hypertensive disorder and cardiovascular disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C03BA11
• Targets: 1 (NAPEPLD)
• Indications: 7 conditions
• Clinical trials: 19
• Chemistry: 365.8 Da · C16H16ClN3O3S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL406
Name	Indapamide
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	3702
ChEBI	CHEBI:5893
ATC	C03BA11
Molecular formula	C16H16ClN3O3S
Molecular weight	365.8
InChIKey	NDDAHWYSQHTHNT-UHFFFAOYSA-N

SMILES: CC1CC2=CC=CC=C2N1NC(=O)C3=CC(=C(C=C3)Cl)S(=O)(=O)N

IUPAC name: 4-chloro-N-(2-methyl-2,3-dihydroindol-1-yl)-3-sulfamoylbenzamide

ChEBI definition: A sulfonamide formed by condensation of the carboxylic group of 4-chloro-3-sulfamoylbenzoic acid with the amino group of 2-methyl-2,3-dihydro-1H-indol-1-amine.

Pharmacological roles (ChEBI): antihypertensive agent, diuretic.

Also known as: Arifon, Bajaten, Cardide sr, Damide, Ethibide xl, Flubest, Fludex, Fludin, Flupamid, Indaflex, Indamide, Indamol

Patent coverage: 4,775 distinct patent families (16,097 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 15,580 (97%) 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
NAPEPLD	N-Acylphosphatidylethanolamine-phospholipase D	Binding	6.24	0%	Q6IQ20

Broader ChEMBL bioactivity targets: 18 (assay-derived). Sample: Survival motor neuron protein, Carbonic anhydrase 2, Carbonic anhydrase 13, Prostaglandin G/H synthase 2, Carbonic anhydrase 7, Lysosomal alpha-glucosidase, Carbonic anhydrase 1, Carbonic anhydrase 3, Carbonic anhydrase 6, Carbonic anhydrase 12.

Bioactivity

ChEMBL activities: 52 potent at pChembl ≥ 5 of 58 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CA7	9.64	Ki	0.23	nM	CHEMBL_ACT_13859516
CA7	9.64	Ki	0.23	nM	CHEMBL_ACT_2491999
CA4	9.48	Kd	0.33	nM	CHEMBL_ACT_18489922
CA14	9.42	Kd	0.38	nM	CHEMBL_ACT_18489762
CA5B	9.34	Kd	0.46	nM	CHEMBL_ACT_18489882
CA6	9	Kd	1.01	nM	CHEMBL_ACT_18489862
CA7	8.84	Kd	1.46	nM	CHEMBL_ACT_18489842
CA9	8.69	Kd	2.03	nM	CHEMBL_ACT_18489822
CA2	8.42	Kd	3.77	nM	CHEMBL_ACT_18489962
CA13	8.39	Kd	4.11	nM	CHEMBL_ACT_18489782
CA5A	8.16	Kd	6.96	nM	CHEMBL_ACT_18489902
CA12	8	Ki	10	nM	CHEMBL_ACT_2492013
CA12	7.91	Kd	12.2	nM	CHEMBL_ACT_18489802
Q9D6N1	7.89	Ki	13	nM	CHEMBL_ACT_2492020
CA9	7.44	Ki	36	nM	CHEMBL_ACT_2492006
CA5B	7.23	Kd	59	nM	CHEMBL_ACT_18490122
CA14	7.2	Kd	63	nM	CHEMBL_ACT_18490023
CA4	7.11	Kd	77	nM	CHEMBL_ACT_18490162
CA13	7	Kd	100	nM	CHEMBL_ACT_13509009
CA13	7	Kd	100	nM	CHEMBL_ACT_3526612
CA3	6.98	Kd	105	nM	CHEMBL_ACT_18489942
CA2	6.89	Kd	130	nM	CHEMBL_ACT_26047529
CA2	6.7	Kd	200	nM	CHEMBL_ACT_3526623
CA13	6.7	Kd	200	nM	CHEMBL_ACT_3526625
CA4	6.67	Ki	213	nM	CHEMBL_ACT_2491971
CA6	6.6	Kd	250	nM	CHEMBL_ACT_13510011
CA7	6.6	Kd	250	nM	CHEMBL_ACT_18490082
CA1	6.58	Kd	261	nM	CHEMBL_ACT_18490043
CA5B	6.56	Ki	274	nM	CHEMBL_ACT_2491985
CA13	6.54	Kd	290	nM	CHEMBL_ACT_18490003

Target pathways

Aggregated over 1 target gene(s): NAPEPLD.

Top Reactome pathways

5 total, by targets touching each:

Pathway	Targets	Genes
Disease	1	NAPEPLD
Retinoid cycle disease events	1	NAPEPLD
Biosynthesis of A2E, implicated in retinal degradation	1	NAPEPLD
Diseases associated with visual transduction	1	NAPEPLD
Diseases of the neuronal system	1	NAPEPLD

Dominant GO biological processes

GO term	Targets
temperature homeostasis	1
phospholipid catabolic process	1
response to isolation stress	1
host-mediated modulation of intestinal microbiota composition	1
positive regulation of inflammatory response	1
N-acylethanolamine metabolic process	1
N-acylphosphatidylethanolamine metabolic process	1
positive regulation of brown fat cell differentiation	1
negative regulation of eating behavior	1
lipid metabolic process	1
phospholipid metabolic process	1
lipid catabolic process	1

Indications & clinical

Indications

7 indications (4 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
hypertensive disorder	4	MONDO:0005044	EFO:0000537
cardiovascular disorder	4	MONDO:0004995	EFO:0000319
congestive heart failure	4	MONDO:0005009	EFO:0000373
preeclampsia	4	MONDO:0005081	EFO:0000668
type 2 diabetes mellitus	3	MONDO:0005148	MONDO:0005148
essential hypertension	3	MONDO:0001134	MONDO:0001134
chronic progressive multiple sclerosis	2	MONDO:0005284	EFO:0003840

Clinical trials

Total trials: 19.

Phase distribution

Phase	Trials
PHASE4	7
Not specified	5
PHASE3	4
PHASE2	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00128518	PHASE4	COMPLETED	IDEAL Study: Identification of the Determinants of the Efficacy of Arterial Blood Pressure Lowering Drugs
NCT00980187	PHASE4	COMPLETED	A Comparison of Indapamide SR 1.5 mg With HCTZ 25 mg, in Combination With an ACE-inhibitor, in Patients With Mild to Moderate AHT and Type 2 DM
NCT01172431	PHASE4	COMPLETED	Indapamide Versus Hydrochlorothiazide in Elderly Hypertensive Patients With Renal Insufficiency
NCT02710539	PHASE4	UNKNOWN	Once-daily Fixed Combination of Three Antihypertensive Drugs
NCT02710552	PHASE4	UNKNOWN	Low-dose Combination of Three Antihypertensive Drugs
NCT04455178	PHASE4	UNKNOWN	The Comparison Between Spironolactone and Indapamide Monotherapy or in Combination With Amlodipine to Reduce the Risk of Heart Failure
NCT05683301	PHASE4	COMPLETED	Treatment Optimisation for Blood Pressure With Single-Pill Combinations in India
NCT01620788	PHASE3	SUSPENDED	Comparison of Losartan Associated With Indapamide Versus Hyzaar® in the Hypertension Treatment
NCT03246555	PHASE3	COMPLETED	Fimasartan in the Senior Subjects
NCT05110898	PHASE3	UNKNOWN	Efficacy and Safety Study of the Fixed-dose Combination of Olmesartan + Indapamide When Compared to the Isolated Drugs in the Treatment of Hypertension.
NCT05878561	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of BR1015 Combination Therapy
NCT06111885	PHASE2	RECRUITING	Indapamide and Chlorthalidone to Reduce Urine Supersaturation for Kidney Stone Prevention
NCT05013463	PHASE2	UNKNOWN	Hydroxychloroquine and Indapamide in SPMS
NCT05103332	PHASE2	COMPLETED	Zilebesiran as Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication (KARDIA-2)
NCT07259733	Not specified	RECRUITING	Rapid Management of Resistant Hypertension in the Public Health System (Fast Control)
NCT01996085	Not specified	COMPLETED	Non-invasive Haemodynamic Assessment in Hypertension
NCT02655029	Not specified	COMPLETED	Study for the Recording of Adherence to Treatment With Perindopril/Indapamide/Amlodipine Fixed Dose Combination
NCT03626506	Not specified	UNKNOWN	Spironolactone Versus Indapamide in Obese and Hypertensive Patients
NCT03722524	Not specified	COMPLETED	The Use of TrIple Fixed-dose Combination in the Treatment of Arterial Hypertension

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 1 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.

2 molecules share ≥1 primary target. Top 2 by shared-target count:

Molecule	Source	Status	Shared targets
HEXACHLOROPHENE	ChEMBL	Phase 4 (approved)	NAPEPLD
Orlistat	PubChem	Approved	NAPEPLD