Chlorothiazide

Summary

Chlorothiazide (CHEMBL842) is an approved small-molecule diuretic (ATC C03AA04) targeting SLC12A3; indicated across 14 conditions including hypertensive disorder and nephrotic syndrome.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C03AA04 (+1 more)
• Targets: 1 (SLC12A3)
• Indications: 14 conditions
• Clinical trials: 5
• Chemistry: 295.7 Da · C7H6ClN3O4S2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL842
Name	Chlorothiazide
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	2720
ChEBI	CHEBI:3640
ATC	C03AA04, C03AH01
Molecular formula	C7H6ClN3O4S2
Molecular weight	295.7
InChIKey	JBMKAUGHUNFTOL-UHFFFAOYSA-N

SMILES: C1=C2C(=CC(=C1Cl)S(=O)(=O)N)S(=O)(=O)N=CN2

IUPAC name: 6-chloro-1,1-dioxo-4H-1lambda6,2,4-benzothiadiazine-7-sulfonamide

ChEBI definition: 4H-1,2,4-benzothiadiazine 1,1-dioxide in which the hydrogen at position is substituted by chlorine and that at position 7 is substituted by a sulfonamide group. A diuretic, it is used for treatment of oedema and hypertension.

Pharmacological roles (ChEBI): diuretic, antihypertensive agent.

Also known as: Chlorothiazide, Clorotiazida, Diuril, Hydrochlorothiazide impurity, chlorothiazide-, NSC-25693, Saluric, Chlorthiazide, SID11110950, SID11110951, SID17389544, SID50105505

Parent form; salt/anhydrous children: CHEMBL1200616

Patent coverage: 13,563 distinct patent families (48,094 SureChEMBL compound mentions), from 4 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).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
SLC12A3	Na-Cl symporter	Inhibition		0.2%	P55017

Broader ChEMBL bioactivity targets: 8 (assay-derived). Sample: Prelamin-A/C, RecQ-like DNA helicase BLM, Thyrotropin receptor, Beta-lactamase, Carbonic anhydrase 1, Muscarinic acetylcholine receptor M1, Nuclear factor NF-kappa-B p105 subunit, Cytochrome P450 3A4.

Bioactivity

ChEMBL activities: 8 potent at pChembl ≥ 5 of 15 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CA1	6.34	IC50	460	nM	CHEMBL_ACT_27123887
LMNA	6.05	Potency	891.3	nM	CHEMBL_ACT_3643598
NFKB1	5.4	Potency	3981	nM	CHEMBL_ACT_3672062
NFKB1	5.4	Potency	3981	nM	CHEMBL_ACT_4585344
TSHR	5.1	Potency	7943	nM	CHEMBL_ACT_3926188
TSHR	5.1	Potency	7943	nM	CHEMBL_ACT_4706808
CYP3A4	5	Potency	10000	nM	CHEMBL_ACT_4977641
CYP3A4	5	Potency	10000	nM	CHEMBL_ACT_5042874

Target pathways

Aggregated over 1 target gene(s): SLC12A3.

Top Reactome pathways

8 total, by targets touching each:

Pathway	Targets	Genes
Disease	1	SLC12A3
Transport of small molecules	1	SLC12A3
R-HSA-425393	1	SLC12A3
SLC-mediated transmembrane transport	1	SLC12A3
Cation-coupled Chloride cotransporters	1	SLC12A3
Defective SLC12A3 causes Gitelman syndrome (GS)	1	SLC12A3
SLC transporter disorders	1	SLC12A3
Disorders of transmembrane transporters	1	SLC12A3

Dominant GO biological processes

GO term	Targets
monoatomic ion transport	1
sodium ion transport	1
cell volume homeostasis	1
sodium ion transmembrane transport	1
chloride ion homeostasis	1
potassium ion homeostasis	1
sodium ion homeostasis	1
renal sodium ion absorption	1
response to salt	1
chloride transmembrane transport	1
response to aldosterone	1
potassium ion import across plasma membrane	1
transmembrane transport	1

Indications & clinical

Indications

8 approved indications. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
hypertensive disorder	4	MONDO:0005044	EFO:0000537
nephrotic syndrome	4	MONDO:0005377	EFO:0004255
congestive heart failure	4	MONDO:0005009	EFO:0000373
cardiovascular disorder	4	MONDO:0004995	EFO:0000319
preeclampsia	4	MONDO:0005081	EFO:0000668
chronic kidney disease	4	MONDO:0005300	EFO:0003884
glomerulonephritis	4	MONDO:0002462	MONDO:0002462
heart failure	4	MONDO:0005252	EFO:0003144

4 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
heart disorder	3	MONDO:0005267	EFO:0003777
atherosclerosis	3	MONDO:0005311	EFO:0003914
coronary artery disorder	3	MONDO:0005010	EFO:0001645
type 2 diabetes mellitus	3	MONDO:0005148	MONDO:0005148

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

Clinical trials

Total trials: 5.

Phase distribution

Phase	Trials
PHASE4	2
Not specified	2
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02606253	PHASE4	COMPLETED	Comparison of Oral or Intravenous Thiazides vs Tolvaptan in Diuretic Resistant Decompensated Heart Failure
NCT03574857	PHASE4	TERMINATED	Prospective Comparison of Metolazone Versus Chlorothiazide for Acute Decompensated Heart Failure With Diuretic Resistance
NCT00000484	PHASE3	COMPLETED	Treatment of Hypertension
NCT07568574	Not specified	ENROLLING_BY_INVITATION	Impact of Medically Supervised Performance-Enhancing Substances (PES) on Elite Athletes
NCT00004360	Not specified	COMPLETED	Study of Genotype and Phenotype Expression in Congenital Nephrogenic Diabetes Insipidus

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 2 clinical and 2 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).