Chlorthalidone

Summary

Chlorthalidone (CHEMBL1055) is an approved small molecule (ATC C03BA04) targeting NAPEPLD, CA1, and CA14; indicated across 23 conditions including hypertensive disorder and cardiovascular disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C03BA04
• Targets: 6 (NAPEPLD, CA1, CA14…)
• Indications: 23 conditions
• Clinical trials: 58
• Chemistry: 338.8 Da · C14H11ClN2O4S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1055
Name	Chlorthalidone
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	2732
ChEBI	CHEBI:3654
ATC	C03BA04
Molecular formula	C14H11ClN2O4S
Molecular weight	338.8
InChIKey	JIVPVXMEBJLZRO-UHFFFAOYSA-N

SMILES: C1=CC=C2C(=C1)C(=O)NC2(C3=CC(=C(C=C3)Cl)S(=O)(=O)N)O

IUPAC name: 2-chloro-5-(1-hydroxy-3-oxo-2H-isoindol-1-yl)benzenesulfonamide

Also known as: Chlortalidone, Chlortalidonum, Chlorthalidone, Chlorthalidone component of clorpres, Chlorthalidone component of combipres, Chlorthalidone component of edarbyclor, Chlorthalidone component of kerledex, Chlorthalidone component of lopressidone, Chlorthalidone component of regroton, Chlorthalidone component of tenoretic, Clortalidona, G-33182

Patent coverage: 5,469 distinct patent families (20,442 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 20,433 (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
NAPEPLD	N-Acylphosphatidylethanolamine-phospholipase D	Binding	6.17	0%	Q6IQ20
CA1	carbonic anhydrase 1	Inhibition	6.46	0%	P00915
CA14	carbonic anhydrase 14	Inhibition	5.38	0%	Q9ULX7
CA4	carbonic anhydrase 4	Inhibition	6.71	0.3%	P22748
CA12	carbonic anhydrase 12	Inhibition	8.35	0.2%	O43570
CA7	carbonic anhydrase 7	Inhibition	8.55	1.6%	P43166

Broader ChEMBL bioactivity targets: 13 (assay-derived). Sample: Microtubule-associated protein tau, Carbonic anhydrase 2, Carbonic anhydrase 13, Carbonic anhydrase 7, Carbonic anhydrase 1, Carbonic anhydrase 3, Carbonic anhydrase 6, Carbonic anhydrase 12, Carbonic anhydrase 14, Carbonic anhydrase 9.

Bioactivity

ChEMBL activities: 15 potent at pChembl ≥ 5 of 16 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CA7	8.55	Ki	2.8	nM	CHEMBL_ACT_2491998
CA12	8.35	Ki	4.5	nM	CHEMBL_ACT_2492012
CA5B	8.05	Ki	9	nM	CHEMBL_ACT_2491984
Q9D6N1	7.82	Ki	15	nM	CHEMBL_ACT_2492019
CA9	7.64	Ki	23	nM	CHEMBL_ACT_2492005
CA2	6.86	Ki	138	nM	CHEMBL_ACT_2491956
CA4	6.71	Ki	196	nM	CHEMBL_ACT_2491970
CA1	6.58	IC50	260	nM	CHEMBL_ACT_27123890
CA1	6.46	Ki	348	nM	CHEMBL_ACT_2491949
CA2	6.17	IC50	677	nM	CHEMBL_ACT_7684179
CA5A	6.04	Ki	917	nM	CHEMBL_ACT_2491977
CA6	5.87	Ki	1347	nM	CHEMBL_ACT_2491991
CA14	5.38	Ki	4130	nM	CHEMBL_ACT_2492026
MAPT	5.25	Potency	5623	nM	CHEMBL_ACT_4507425
MAPT	5.05	Potency	8912	nM	CHEMBL_ACT_4049146

Target pathways

Aggregated over 6 target gene(s): NAPEPLD, CA1, CA14, CA4, CA12, CA7.

Top Reactome pathways

17 total, by targets touching each:

Pathway	Targets	Genes
Metabolism	5	CA1, CA12, CA14, CA4, CA7
Reversible hydration of carbon dioxide	5	CA1, CA12, CA14, CA4, CA7
Erythrocytes take up carbon dioxide and release oxygen	2	CA1, CA4
Erythrocytes take up oxygen and release carbon dioxide	2	CA1, CA4
O2/CO2 exchange in erythrocytes	2	CA1, CA4
Transport of small molecules	2	CA1, CA4
Cytokine Signaling in Immune system	1	CA1
Disease	1	NAPEPLD
Immune System	1	CA1
Retinoid cycle disease events	1	NAPEPLD
Biosynthesis of A2E, implicated in retinal degradation	1	NAPEPLD
Diseases associated with visual transduction	1	NAPEPLD
Interleukin-12 family signaling	1	CA1
Signaling by Interleukins	1	CA1
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1	CA1
Interleukin-12 signaling	1	CA1
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
response to fructose	1
bicarbonate transport	1
estrous cycle	1

Indications & clinical

Indications

23 indications (9 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
chronic kidney disease	4	MONDO:0005300	EFO:0003884
heart failure	4	MONDO:0005252	EFO:0003144
congestive heart failure	4	MONDO:0005009	EFO:0000373
preeclampsia	4	MONDO:0005081	EFO:0000668
nephrotic syndrome	4	MONDO:0005377	EFO:0004255
glomerulonephritis	4	MONDO:0002462	MONDO:0002462
cerebrovascular disorder	3	MONDO:0011057	EFO:0003763
heart disorder	3	MONDO:0005267	EFO:0003777
diabetes mellitus	3	MONDO:0005015	EFO:0000400
myocardial infarction	3	MONDO:0005068	EFO:0000612
atherosclerosis	3	MONDO:0005311	EFO:0003914
myocardial ischemia	3	MONDO:0024644	EFO:1001375
coronary artery disorder	3	MONDO:0005010	EFO:0001645
essential hypertension	3	MONDO:0001134	MONDO:0001134
type 2 diabetes mellitus	3	MONDO:0005148	MONDO:0005148
vascular disorder	3	MONDO:0005385	EFO:0004264
type 1 diabetes mellitus	2	MONDO:0005147	MONDO:0005147
nephrolithiasis	2	MONDO:0008171	EFO:0004253

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

Clinical trials

Total trials: 58.

Phase distribution

Phase	Trials
PHASE3	18
PHASE4	16
PHASE2	9
Not specified	9
PHASE1	5
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05593055	PHASE4	RECRUITING	Mineralocorticoid Receptor, Coronary Microvascular Function, and Cardiac Efficiency in Hypertension
NCT06041529	PHASE4	ACTIVE_NOT_RECRUITING	Study to Evaluate the Efficacy and Safety of TEL/AML/CTD in Elderly Patients With Essential Hypertension
NCT07225764	PHASE4	RECRUITING	CaOx Stone Prevention
NCT01203852	PHASE4	COMPLETED	Pharmacogenomic Evaluation of Antihypertensive Responses 2
NCT01368536	PHASE4	TERMINATED	Study to Evaluate the Efficacy and Safety of the Combination of Valturna and Amlodipine or Valturna and Chlorthalidone Versus Valturna Alone in Patients With Stage 2 Hypertension and Diabetes
NCT01748123	PHASE4	WITHDRAWN	EBMtrialcentral- Comparing Initial Diuretic Therapies Using a Collaborative Network
NCT01750294	PHASE4	COMPLETED	A Pilot Study of Chlorthalidone Among Patients With Poorly Controlled Hypertension and CKD
NCT01822860	PHASE4	WITHDRAWN	Chlorthalidone Compared to Hydrochlorothiazide on Endothelial Function
NCT02030314	PHASE4	WITHDRAWN	The Management of Resistant Hypertension in Kidney Transplant Patients Using Chlorthalidone
NCT02100462	PHASE4	UNKNOWN	Chlorthalidone and HCTZ Impacts on Platelet Activation
NCT02502981	PHASE4	UNKNOWN	Comparing the Effects of Spironolactone With Chlortalidone on LV Mass in Patients With CKD
NCT02847338	PHASE4	COMPLETED	Comparison of Optimal Hypertension Regimens
NCT03666351	PHASE4	COMPLETED	Study to Evaluate the Effect on Improvement of LVH by the Control of BP in Hypertension Patients With AV Disease
NCT05171686	PHASE4	COMPLETED	Diuretics and Volume Overload in Early CKD
NCT05275907	PHASE4	WITHDRAWN	Mechanism of Hypertension Treatments in Liver Transplant Recipients (BLOCK LTR-HTN)
NCT05915286	PHASE4	TERMINATED	Diuretic Use in Hemodialysis Patients With Residual Renal Function
NCT00000513	PHASE3	COMPLETED	Trial of Antihypertensive Intervention Management
NCT00000514	PHASE3	COMPLETED	Systolic Hypertension in the Elderly Program (SHEP)
NCT00000525	PHASE3	COMPLETED	Diuretics, Hypertension, and Arrhythmias Clinical Trial
NCT00000542	PHASE3	COMPLETED	Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)
NCT00241839	PHASE3	COMPLETED	Uric Acid and Hypertension in African Americans
NCT00591773	PHASE3	COMPLETED	Efficacy and Safety of Azilsartan Medoxomil Co-Administered With Chlorthalidone in Participants With Essential Hypertension
NCT00818883	PHASE3	COMPLETED	Efficacy and Safety of Azilsartan Medoxomil and Chlorthalidone in Participants With Moderate to Severe Hypertension
NCT00846365	PHASE3	COMPLETED	Efficacy and Safety of Azilsartan Medoxomil Plus Chlorthalidone in Participants With Moderate to Severe Hypertension
NCT00847626	PHASE3	COMPLETED	Efficacy and Safety of Azilsartan Medoxomil Combined With Chlorthalidone in Participants With Moderate to Severe Hypertension
NCT00996281	PHASE3	COMPLETED	Safety and Tolerability of Azilsartan Medoxomil Plus Chlorthalidone Compared to Olmesartan Medoxomil Plus Hydrochlorothiazide in Participants With Essential Hypertension
NCT01033071	PHASE3	COMPLETED	Efficacy and Safety of Azilsartan Medoxomil and Chlorthalidone Compared to Olmesartan Medoxomil and Hydrochlorothiazide in Participants With Moderate to Severe Hypertension.
NCT01309828	PHASE3	COMPLETED	Long-Term Safety of Azilsartan Medoxomil and Chlorthalidone Compared to Olmesartan Medoxomil and Hydrochlorothiazide in Participants With Hypertension and Kidney Disease
NCT02185417	PHASE3	COMPLETED	Diuretic Comparison Project
NCT02521233	PHASE3	WITHDRAWN	Efficacy and Safety of Candesartan Associated With Chlorthalidone in Essential Arterial Hypertension Control
NCT02521246	PHASE3	WITHDRAWN	Efficacy and Safety of Candesartan Associated With Chlorthalidone Versus Losartan Associated With Hydrochlorothiazide (Hyzaar®) in Essential Hypertension Control
NCT02644395	PHASE3	COMPLETED	Thiazide Diuretics for Hypertension in Kidney Transplant Recipients Using Tacrolimus
NCT03928145	PHASE3	UNKNOWN	Efficacy of Chlorthalidone and Hydrochlorothiazide Combined With Amiloride on Blood Pressure in Primary Hypertension.
NCT05920005	PHASE3	COMPLETED	Candesartan Cilexetil + Chlorthalidone + Amlodipine Versus Exforge HCT®️ for Systemic Arterial Hypertension
NCT06111885	PHASE2	RECRUITING	Indapamide and Chlorthalidone to Reduce Urine Supersaturation for Kidney Stone Prevention
NCT00000499	PHASE2	COMPLETED	Systolic Hypertension in the Elderly Program (SHEP) (Pilot Study)
NCT00000522	PHASE2	COMPLETED	Treatment of Mild Hypertension Study (TOMHS)
NCT02236520	PHASE2	COMPLETED	Tissue Sodium in Pre-hypertensive Patients
NCT02841280	PHASE2	COMPLETED	Chlorthalidone in Chronic Kidney Disease
NCT03325114	PHASE2	TERMINATED	Safety and Efficacy of Chlorthalidone in Type 1 Diabetes

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 7 clinical and 7 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.

94 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
ACETAMINOPHEN	ChEMBL + PubChem	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
ACETAZOLAMIDE	ChEMBL + PubChem	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
CELECOXIB	ChEMBL + PubChem	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
COUMARIN	ChEMBL + PubChem	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
DICHLORPHENAMIDE	ChEMBL + PubChem	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
DOBUTAMINE	ChEMBL + PubChem	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
FUROSEMIDE	ChEMBL + PubChem	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
LACOSAMIDE	ChEMBL + PubChem	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
SALICYLIC ACID	ChEMBL + PubChem	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
BORTEZOMIB	ChEMBL	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
BRINZOLAMIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
DORZOLAMIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
ETHOXZOLAMIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
FAMOTIDINE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
IMATINIB	ChEMBL	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
INDAPAMIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
LEVETIRACETAM	ChEMBL	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
MAFENIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
METHAZOLAMIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
NILOTINIB	ChEMBL	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
SULFANILAMIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
TOPIRAMATE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
TRICHLORMETHIAZIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
TRIENTINE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
VALDECOXIB	ChEMBL	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
VERALIPRIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
ZONISAMIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA14, CA4, CA7
CAFFEIC ACID	ChEMBL	Phase 3	CA1, CA12, CA14, CA4, CA7
CURCUMIN	ChEMBL	Phase 3	CA1, CA12, CA14, CA4, CA7
QUERCETIN	ChEMBL	Phase 3	CA1, CA12, CA14, CA4, CA7
RESVERATROL	ChEMBL	Phase 3	CA1, CA12, CA14, CA4, CA7
SACCHARIN	ChEMBL	Phase 3	CA1, CA12, CA14, CA4, CA7
SPERMIDINE	ChEMBL	Phase 3	CA1, CA12, CA14, CA4, CA7
COUMAPHOS	ChEMBL	Phase 2	CA1, CA12, CA14, CA4, CA7
ELLAGIC ACID	ChEMBL	Phase 2	CA1, CA12, CA14, CA4, CA7
GALLIC ACID	ChEMBL	Phase 2	CA1, CA12, CA14, CA4, CA7
IROSUSTAT	ChEMBL	Phase 2	CA1, CA12, CA14, CA4, CA7
PCI-27483	ChEMBL	Phase 2	CA1, CA12, CA14, CA4, CA7
SONEPIPRAZOLE	ChEMBL	Phase 2	CA1, CA12, CA14, CA4, CA7
HYDROQUINONE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA14, CA4
PHENOL	ChEMBL	Phase 4 (approved)	CA1, CA12, CA14, CA4
PYRITHIONE ZINC	ChEMBL	Phase 4 (approved)	CA12, CA14, CA4, CA7
THIMEROSAL	ChEMBL	Phase 3	CA12, CA14, CA4, CA7
CARZENIDE	ChEMBL	Phase 2	CA1, CA12, CA14, CA7
INDISULAM	ChEMBL	Phase 2	CA1, CA12, CA14, CA7
SULFASUCCINAMIDE	ChEMBL	Phase 2	CA1, CA12, CA14, CA4
SULPIRIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
P-TOLUENESULFONAMIDE	ChEMBL	Phase 3	CA1, CA12, CA7
DAIDZEIN	ChEMBL	Phase 2	CA12, CA4, CA7
DITIOCARB	ChEMBL	Phase 2	CA1, CA12, CA4
ISOQUERCETIN	ChEMBL	Phase 2	CA12, CA4, CA7
LUTEOLIN	ChEMBL	Phase 2	CA12, CA4, CA7
SODIUM CYCLAMATE	ChEMBL	Phase 2	CA12, CA14, CA7
Sildenafil	PubChem	Approved	CA14, CA4, CA7
HYDROCHLOROTHIAZIDE	ChEMBL + PubChem	Phase 4 (approved)	CA1, CA14
PAZOPANIB	ChEMBL + PubChem	Phase 4 (approved)	CA1, CA12
SODIUM	ChEMBL	Phase 4 (approved)	CA1, CA4
SULTHIAME	ChEMBL	Phase 4 (approved)	CA1, CA7
ZOLEDRONIC ACID	ChEMBL	Phase 4 (approved)	CA12, CA14
PRITELIVIR	ChEMBL	Phase 3	CA1, CA12