Cyclothiazide

Summary

Cyclothiazide (CHEMBL61593) is an approved small-molecule diuretic (ATC C03AA09) targeting GRIA1, GRIA2, and GRIA3; indicated across 1 condition including cardiovascular disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C03AA09
• Targets: 5 (GRIA1, GRIA2, GRIA3…)
• Indications: 1 condition
• Chemistry: 389.9 Da · C14H16ClN3O4S2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL61593
Name	Cyclothiazide
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	2910
ChEBI	CHEBI:31448
ATC	C03AA09
Molecular formula	C14H16ClN3O4S2
Molecular weight	389.9
InChIKey	BOCUKUHCLICSIY-UHFFFAOYSA-N

SMILES: C1C2CC(C1C=C2)C3NC4=CC(=C(C=C4S(=O)(=O)N3)S(=O)(=O)N)Cl

IUPAC name: 3-(2-bicyclo[2.2.1]hept-5-enyl)-6-chloro-1,1-dioxo-3,4-dihydro-2H-1lambda6,2,4-benzothiadiazine-7-sulfonamide

ChEBI definition: 3,4-Dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide substituted at positions 3, 5 and 6 by a 2-norbornen-5-yl group, chlorine, and a sulfonamide group, respectively. A thiazide diuretic, it has been used in the management of hypertension and oedema.

Pharmacological roles (ChEBI): diuretic, antihypertensive agent.

Also known as: Anhydron, Ciclotiazida, Cyclothiazide, Fluidil, NSC-758431, cyclothiazide, SID26751850, SID50104549, SID85230990, SID90341445, CYCLOTHIAZIDE, SID56424127

Patent coverage: 1,248 distinct patent families (4,410 SureChEMBL compound mentions), from 1 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
GRIA1	GluA1	Positive	4.72	0.1%	P42261
GRIA2	GluA2	Positive	5.65	0%	P42262
GRIA3	GluA3	Positive	4.86	0%	P42263
GRIA4	GluA4	Positive	5.41	0.2%	P48058
SLC12A3	Na-Cl symporter	Inhibition		0.2%	P55017

Broader ChEMBL bioactivity targets: 14 (assay-derived). Sample: Prelamin-A/C, ATP-dependent DNA helicase Q1, RecQ-like DNA helicase BLM, Ferritin light chain, Histone-lysine N-methyltransferase 2A, Thyroid hormone receptor beta, Glutamate receptor 1, Glutamate receptor ionotropic, AMPA, Muscarinic acetylcholine receptor M1, Glutamate receptor 4.

Bioactivity

ChEMBL activities: 13 potent at pChembl ≥ 5 of 21 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
THRB	6.85	Potency	141.3	nM	CHEMBL_ACT_4019088
GRIA1	6	EC50	1000	nM	CHEMBL_ACT_3266569
GRIA1	5.7	EC50	2000	nM	CHEMBL_ACT_3266654
GRIA2	5.65	EC50	2240	nM	CHEMBL_ACT_3266657
GRIA4	5.42	EC50	3800	nM	CHEMBL_ACT_1770033
GRIA4	5.42	EC50	3800	nM	CHEMBL_ACT_943396
P19490	5.21	IC50	6100	nM	CHEMBL_ACT_249628
LMNA	5.2	Potency	6310	nM	CHEMBL_ACT_4403424
GRIA1	5.18	EC50	6600	nM	CHEMBL_ACT_3266650
GRIA2	5.12	EC50	7600	nM	CHEMBL_ACT_16458051
P19491	5.12	EC50	7600	nM	CHEMBL_ACT_2374468
LMNA	5.05	Potency	8912	nM	CHEMBL_ACT_3651750
GRIA1	5	EC50	10000	nM	CHEMBL_ACT_3266655

Target pathways

Aggregated over 5 target gene(s): GRIA1, GRIA2, GRIA3, GRIA4, SLC12A3.

Top Reactome pathways

17 total, by targets touching each:

Pathway	Targets	Genes
Activation of AMPA receptors	4	GRIA1, GRIA2, GRIA3, GRIA4
Trafficking of GluR2-containing AMPA receptors	4	GRIA1, GRIA2, GRIA3, GRIA4
Unblocking of NMDA receptors, glutamate binding and activation	4	GRIA1, GRIA2, GRIA3, GRIA4
Trafficking of AMPA receptors	3	GRIA1, GRIA3, GRIA4
Synaptic adhesion-like molecules	3	GRIA1, GRIA3, GRIA4
Long-term potentiation	2	GRIA1, GRIA2
Disease	1	SLC12A3
COPII-mediated vesicle transport	1	GRIA1
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
Cargo concentration in the ER	1	GRIA1
MECP2 regulates neuronal receptors and channels	1	GRIA2

Dominant GO biological processes

GO term	Targets
monoatomic ion transport	5
synaptic transmission, glutamatergic	4
modulation of chemical synaptic transmission	4
monoatomic ion transmembrane transport	4
ionotropic glutamate receptor signaling pathway	4
regulation of postsynaptic membrane potential	4
regulation of presynaptic membrane potential	3
signal transduction	2
chemical synaptic transmission	2
long-term synaptic potentiation	2
calcium-mediated signaling	2
glutamate receptor signaling pathway	2
regulation of receptor recycling	1
synapse assembly	1
long-term memory	1

Indications & clinical

Indications

1 indication (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).

Indication	Trial phase	MONDO	EFO
cardiovascular disorder	4	MONDO:0004995	EFO:0000319

Clinical trials

Total trials: 0.

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

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.

7 molecules share ≥1 primary target. Top 7 by shared-target count:

Molecule	Source	Status	Shared targets
GLUTAMIC ACID	ChEMBL + PubChem	Phase 3 (approved)	GRIA1, GRIA2, GRIA3, GRIA4
KAINIC ACID	ChEMBL	Phase 2	GRIA1, GRIA2, GRIA3, GRIA4
SELFOTEL	ChEMBL	Phase 2	GRIA1, GRIA2, GRIA3, GRIA4
TEZAMPANEL	ChEMBL	Phase 2	GRIA1, GRIA2, GRIA3, GRIA4
PERAMPANEL	ChEMBL + PubChem	Phase 4 (approved)	GRIA1, GRIA3
FARAMPATOR	ChEMBL	Phase 2	GRIA3, GRIA4
MIBAMPATOR	ChEMBL	Phase 2	GRIA4