Diazoxide

Summary

Diazoxide (CHEMBL181) is an approved small-molecule antihypertensive agent (ATC V03AH01) targeting KCNJ8 and KCNJ11; indicated across 7 conditions including hypertensive disorder and hypoglycemia.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: V03AH01 (+1 more)
• Targets: 2 (KCNJ8, KCNJ11)
• Indications: 7 conditions
• Clinical trials: 16
• Chemistry: 230.67 Da · C8H7ClN2O2S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL181
Name	Diazoxide
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	3019
ChEBI	CHEBI:4495
ATC	V03AH01, C02DA01
Molecular formula	C8H7ClN2O2S
Molecular weight	230.67
InChIKey	GDLBFKVLRPITMI-UHFFFAOYSA-N

SMILES: CC1=NS(=O)(=O)C2=C(N1)C=CC(=C2)Cl

IUPAC name: 7-chloro-3-methyl-4H-1lambda6,2,4-benzothiadiazine 1,1-dioxide

ChEBI definition: A benzothiadiazine that is the S,S-dioxide of 2H-1,2,4-benzothiadiazine which is substituted at position 3 by a methyl group and at position 7 by chlorine. A peripheral vasodilator, it increases the concentration of glucose in the plasma and inhibits the secretion of insulin by the β- cells of the pancreas. It is used orally in the management of intractable hypoglycaemia and intravenously in the management of hypertensive emergencies.

Pharmacological roles (ChEBI): antihypertensive agent, sodium channel blocker, vasodilator agent, K-ATP channel agonist, β-adrenergic agonist, cardiotonic drug, bronchodilator agent, sympathomimetic agent, diuretic.

Also known as: Diazoxide, Diazoxido, Diazoxidum, Eudemine, Eudemine injection, Eudimine, Hyperstat, Hypertonalum, Mutabase, NSC-64198, NSC-76130, Proglycem

Parent form; salt/anhydrous children: CHEMBL4297276

Patent coverage: 7,718 distinct patent families (27,974 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
KCNJ8	Kir6.1	Agonist		0%	Q15842
KCNJ11	Kir6.2	Agonist	4.2	0.1%	Q14654

Broader ChEMBL bioactivity targets: 12 (assay-derived). Sample: Nuclear receptor ROR-gamma, Survival motor neuron protein, Prelamin-A/C, Ferritin light chain, Thyroid hormone receptor beta, Thyrotropin receptor, Beta-lactamase, Sulfonylurea receptor 1, Kir6.2, Cytochrome P450 2D6, Cytochrome P450 1A2.

Bioactivity

ChEMBL activities: 13 potent at pChembl ≥ 5 of 28 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
LMNA	6.95	Potency	112.2	nM	CHEMBL_ACT_3664168
ALDH1A1	6.94	Potency	113.8	nM	CHEMBL_ACT_4177872
LMNA	6.8	Potency	158.5	nM	CHEMBL_ACT_3649371
P02791	6.65	Potency	223.9	nM	CHEMBL_ACT_4496932
SMN1	5.8	Potency	1585	nM	CHEMBL_ACT_3878864
CYP1A2	5.7	AC50	1995	nM	CHEMBL_ACT_6003214
CYP1A2	5.5	AC50	3162	nM	CHEMBL_ACT_6003561
LMNA	5.45	Potency	3548	nM	CHEMBL_ACT_4403443
THRB	5.2	Potency	6310	nM	CHEMBL_ACT_4014086
CYP2D6	5.1	Potency	7943	nM	CHEMBL_ACT_5002468
CYP2D6	5.1	AC50	7943	nM	CHEMBL_ACT_5988634
ABCC8	5.06	EC50	8800	nM	CHEMBL_ACT_208097
ABCC8	5.06	EC50	8800	nM	CHEMBL_ACT_426685

Target pathways

Aggregated over 2 target gene(s): KCNJ8, KCNJ11.

Top Reactome pathways

17 total, by targets touching each:

Pathway	Targets	Genes
Neuronal System	2	KCNJ11, KCNJ8
ATP sensitive Potassium channels	2	KCNJ11, KCNJ8
Inwardly rectifying K+ channels	2	KCNJ11, KCNJ8
Potassium Channels	2	KCNJ11, KCNJ8
Metabolism	1	KCNJ11
Integration of energy metabolism	1	KCNJ11
Disease	1	KCNJ11
Transport of small molecules	1	KCNJ11
ABC-family protein mediated transport	1	KCNJ11
Muscle contraction	1	KCNJ11
Regulation of insulin secretion	1	KCNJ11
Cardiac conduction	1	KCNJ11
Ion homeostasis	1	KCNJ11
ABC transporter disorders	1	KCNJ11
Disorders of transmembrane transporters	1	KCNJ11
Defective ABCC9 causes CMD10, ATFB12 and Cantu syndrome	1	KCNJ11
Defective ABCC8 can cause hypo- and hyper-glycemias	1	KCNJ11

Dominant GO biological processes

GO term	Targets
response to hypoxia	2
response to ischemia	2
ventricular cardiac muscle tissue development	2
potassium ion transport	2
apoptotic process	2
determination of adult lifespan	2
response to xenobiotic stimulus	2
response to ATP	2
regulation of monoatomic ion transmembrane transport	2
CAMKK-AMPK signaling cascade	2
potassium ion transmembrane transport	2
obsolete inorganic cation transmembrane transport	2
response to resveratrol	2
potassium ion import across plasma membrane	2
action potential	2

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
hypoglycemia	4	MONDO:0004946	HP:0001943
hyperinsulinism	4	MONDO:0002177	MONDO:0002177
obesity disorder	3	MONDO:0011122	EFO:0001073
type 2 diabetes mellitus	2	MONDO:0005148	MONDO:0005148
depressive disorder	1	MONDO:0002050	MONDO:0002050

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

Clinical trials

Total trials: 16.

Phase distribution

Phase	Trials
PHASE2	6
PHASE4	5
Not specified	2
PHASE3	1
PHASE2/PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00131755	PHASE4	COMPLETED	Efficacy of Diazoxide in Type 1 Diabetes
NCT01028846	PHASE4	TERMINATED	Central Mechanisms That Regulate Glucose Metabolism in Humans
NCT01488136	PHASE4	COMPLETED	Use of Diazoxide in Acute Hypoglycaemia
NCT02779257	PHASE4	WITHDRAWN	Pasireotide Treatment for Neuroendocrine Tumor
NCT03608163	PHASE4	TERMINATED	Novel Approach for the Prevention of Hypoglycemia Associated Autonomic Failure (HAAF)
NCT00306683	PHASE3	COMPLETED	Effect of Diazoxide on the Obesity Secondary to Hypothalamic-pituitary Lesions
NCT00994149	PHASE2/PHASE3	UNKNOWN	Diazoxide In the Management Of Hypoglycemic Neonates
NCT03540758	PHASE2	RECRUITING	Regulation of Endogenous Glucose Production by Central KATP Channels
NCT00151684	PHASE2	COMPLETED	Diazoxide-Mediated Insulin Suppression in Hyperinsulinemic Obese Men
NCT00631033	PHASE2	COMPLETED	DZX Mediated Insulin Suppression in Obese Men
NCT00892073	PHASE2	COMPLETED	Hypothalamic Obesity Following Craniopharyngioma Surgery: A Pilot Trial of Combined Metformin and Diazoxide Therapy
NCT02049385	PHASE1/PHASE2	TERMINATED	Does Enhanced Glutamate Transporter Function Produce Antidepressant Effects in People With Major Depression?
NCT03566511	PHASE2	TERMINATED	Use of Functional MRI to Assess Functional Hypothalamic Activation in Response to Diazoxide
NCT03685773	PHASE2	WITHDRAWN	The Role of Hepatic Denervation in the Dysregulation of Glucose Metabolism in Liver Transplant Recipients
NCT00184821	Not specified	COMPLETED	Ischemic Injury and Ischemic Preconditioning in Diabetes
NCT00683774	Not specified	COMPLETED	Insulin and Polycystic Ovary Syndrome

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
glyburide	ChEMBL + PubChem	Phase 4 (approved)	KCNJ11, KCNJ8
CROMAKALIM	ChEMBL	Phase 2	KCNJ11, KCNJ8
PROPAFENONE	ChEMBL + PubChem	Phase 4 (approved)	KCNJ11
PINACIDIL	ChEMBL	Phase 4 (approved)	KCNJ11
CLAMIKALANT	ChEMBL	Phase 2	KCNJ11
TIFENAZOXIDE	ChEMBL	Phase 2	KCNJ11
Berberine Chloride	PubChem	Approved	KCNJ11