Doxazosin

Summary

Doxazosin (CHEMBL707) is an approved small-molecule antihypertensive agent (ATC C02CA04) targeting ADRA1A, ADRA1B, and ADRA1D; indicated across 20 conditions including hypertensive disorder and benign prostatic hyperplasia.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C02CA04
• Targets: 3 (ADRA1A, ADRA1B, ADRA1D)
• Indications: 20 conditions
• Clinical trials: 34
• Chemistry: 451.5 Da · C23H25N5O5

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL707
Name	Doxazosin
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	3157
ChEBI	CHEBI:4708
ATC	C02CA04
Molecular formula	C23H25N5O5
Molecular weight	451.5
InChIKey	RUZYUOTYCVRMRZ-UHFFFAOYSA-N

SMILES: COC1=C(C=C2C(=C1)C(=NC(=N2)N3CCN(CC3)C(=O)C4COC5=CC=CC=C5O4)N)OC

IUPAC name: [4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-(2,3-dihydro-1,4-benzodioxin-3-yl)methanone

ChEBI definition: A member of the class of quinazolines that is quinazoline substituted by an amino group at position 4, methoxy groups at positions 6 and 7 and a piperazin-1-yl group at position 2 which in turn is substituted by a 2,3-dihydro-1,4-benzodioxin-2-ylcarbonyl group at position 4. An antihypertensive agent, it is used in the treatment of high blood pressure.

Pharmacological roles (ChEBI): antihypertensive agent, α-adrenergic antagonist, antineoplastic agent, vasodilator agent, antihyperplasia drug.

Also known as: C02CA04, Doxazosin, Doxazosina, Doxazosine, UK-33274, doxazosin, SID90341261, SID124883384, SID50105246, DOXAZOSINE, DOXAZOSIN, C0164998

Parent form; salt/anhydrous children: CHEMBL1200561

Patent coverage: 6,972 distinct patent families (24,931 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 24,872 (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
ADRA1A	α1A-adrenoceptor	Antagonist	9.3		P35348
ADRA1B	α1B-adrenoceptor	Antagonist	9.1	0%	P35368
ADRA1D	α1D-adrenoceptor	Antagonist	9.1	0.2%	P25100

Broader ChEMBL bioactivity targets: 33 (assay-derived). Sample: 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Adrenergic receptor alpha-1, Alpha-2C adrenergic receptor, Histamine H2 receptor, Alpha-2B adrenergic receptor, D(1A) dopamine receptor, Thromboxane A2 receptor, Adrenergic receptor alpha-1, Beta-2 adrenergic receptor.

Bioactivity

ChEMBL activities: 77 potent at pChembl ≥ 5 of 88 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P15823	9.51	Kd	0.31	nM	CHEMBL_ACT_2678029
P15823	9.51	Kd	0.31	nM	CHEMBL_ACT_861083
ADRA1D	9.49	Ki	0.32	nM	CHEMBL_ACT_18343296
P15823	9.38	Ki	0.42	nM	CHEMBL_ACT_7683755
ADRA1A	9.27	Ki	0.54	nM	CHEMBL_ACT_1657094
ADRA1A	9.27	Ki	0.54	nM	CHEMBL_ACT_2678007
ADRA1B	9.2	Ki	0.63	nM	CHEMBL_ACT_18343308
P43140	9.2	Ki	0.63	nM	CHEMBL_ACT_7683753
P43140	9.13	IC50	0.74	nM	CHEMBL_ACT_18361422
ADRA1B	9.13	Ki	0.74	nM	CHEMBL_ACT_305045
P15823	9.12	IC50	0.75	nM	CHEMBL_ACT_7683754
ADRA1A	9.11	Ki	0.78	nM	CHEMBL_ACT_18343320
ADRA1B	9.09	Ki	0.81	nM	CHEMBL_ACT_1657114
ADRA1D	9.09	Ki	0.81	nM	CHEMBL_ACT_1657129
ADRA1B	9.09	Ki	0.81	nM	CHEMBL_ACT_2678013
ADRA1D	9.09	Ki	0.81	nM	CHEMBL_ACT_2678019
ADRA1B	9	Ki	1	nM	CHEMBL_ACT_271268
P23944	8.97	Kd	1.07	nM	CHEMBL_ACT_2678034
P15823	8.96	Ki	1.1	nM	CHEMBL_ACT_1004251
ADRA1D	8.92	Ki	1.2	nM	CHEMBL_ACT_305044
P43140	8.81	IC50	1.55	nM	CHEMBL_ACT_7683752
ADRA1D	8.78	Ki	1.66	nM	CHEMBL_ACT_7683757
P43140	8.69	Kd	2.04	nM	CHEMBL_ACT_2678024
P43140	8.69	Kd	2.04	nM	CHEMBL_ACT_861082
P15823	8.66	Ki	2.2	nM	CHEMBL_ACT_994399
P15823	8.59	Ki	2.6	nM	CHEMBL_ACT_1023512
ADRA1A	8.59	Ki	2.6	nM	CHEMBL_ACT_305046
ADRA1A	8.5	Ki	3.16	nM	CHEMBL_ACT_271267
ADRA1A	8.49	AC50	3.2	nM	CHEMBL_ACT_25138433
ADRA1D	8.47	IC50	3.38	nM	CHEMBL_ACT_7683756

Target pathways

Aggregated over 3 target gene(s): ADRA1A, ADRA1B, ADRA1D.

Top Reactome pathways

9 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	3	ADRA1A, ADRA1B, ADRA1D
Signaling by GPCR	3	ADRA1A, ADRA1B, ADRA1D
Class A/1 (Rhodopsin-like receptors)	3	ADRA1A, ADRA1B, ADRA1D
Amine ligand-binding receptors	3	ADRA1A, ADRA1B, ADRA1D
GPCR downstream signalling	3	ADRA1A, ADRA1B, ADRA1D
Adrenoceptors	3	ADRA1A, ADRA1B, ADRA1D
G alpha (q) signalling events	3	ADRA1A, ADRA1B, ADRA1D
G alpha (12/13) signalling events	3	ADRA1A, ADRA1B, ADRA1D
GPCR ligand binding	3	ADRA1A, ADRA1B, ADRA1D

Dominant GO biological processes

GO term	Targets
signal transduction	3
G protein-coupled receptor signaling pathway	3
phospholipase C-activating G protein-coupled receptor signaling pathway	3
positive regulation of cytosolic calcium ion concentration	3
cell-cell signaling	3
positive regulation of MAPK cascade	3
adenylate cyclase-activating adrenergic receptor signaling pathway	3
neuron-glial cell signaling	3
adrenergic receptor signaling pathway	3
positive regulation of cardiac muscle hypertrophy	2
intracellular signal transduction	2
positive regulation of vasoconstriction	2
regulation of muscle contraction	2
regulation of vasoconstriction	2
regulation of cardiac muscle contraction	2

Indications & clinical

Indications

20 indications (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
hypertensive disorder	4	MONDO:0005044	EFO:0000537
benign prostatic hyperplasia	3	MONDO:0010811	EFO:0000284
diabetes mellitus	3	MONDO:0005015	EFO:0000400
myocardial infarction	3	MONDO:0005068	EFO:0000612
heart failure	3	MONDO:0005252	EFO:0003144
myocardial ischemia	3	MONDO:0024644	EFO:1001375
nephrolithiasis	3	MONDO:0008171	EFO:0004253
adrenal gland pheochromocytoma	3	MONDO:0004974	EFO:0000239
paraganglioma	3	MONDO:0000448	EFO:1000453
post-traumatic stress disorder	2	MONDO:0005146	EFO:0001358
cocaine dependence	2	MONDO:0005186	EFO:0002610
nicotine dependence	2	MONDO:0008575	EFO:0003768
heart disorder	2	MONDO:0005267	EFO:0003777
alcohol abuse	2	MONDO:0002046	MONDO:0007079
cardiovascular disorder	2	MONDO:0004995	EFO:0000319
vascular disorder	2	MONDO:0005385	EFO:0004264
drug dependence	1	MONDO:0005303	EFO:0003890
erectile dysfunction	1	MONDO:0005362	EFO:0004234

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

Clinical trials

Total trials: 34.

Phase distribution

Phase	Trials
PHASE4	9
PHASE2	8
PHASE1	8
PHASE3	4
Not specified	3
PHASE2/PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00130156	PHASE4	COMPLETED	Effects of Combination Therapy With Alpha-1 Blocker (Bunazosin or Doxazosin) in the Treatment of Patients With Mild to Moderate Essential Hypertension
NCT00285519	PHASE4	COMPLETED	Japan Morning Surge-1 Study
NCT00295542	PHASE4	COMPLETED	Ambulatory Blood Pressure Monitoring in the Prediction of Cardiovascular Events and Effects of Chronotherapy
NCT00535925	PHASE4	COMPLETED	Nephropathy In Type 2 Diabetes and Cardio-renal Events
NCT00661895	PHASE4	COMPLETED	Black Education and Treatment of Hypertension (BEAT HTN)
NCT01379898	PHASE4	COMPLETED	Phenoxybenzamine Versus Doxazosin in PCC Patients
NCT01798992	PHASE4	COMPLETED	Effect of Beta-blockers on Structural Remodeling and Gene Expression in the Failing Human Heart
NCT02369081	PHASE4	UNKNOWN	Optimum Treatment for Drug-Resistant Hypertension
NCT02901977	PHASE4	COMPLETED	Doxazosin and Ramipril in Hypertension
NCT00000542	PHASE3	COMPLETED	Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)
NCT00021814	PHASE3	COMPLETED	Medical Therapy of Prostatic Symptoms
NCT00713739	PHASE3	UNKNOWN	Alfuzosin for Medical Expulsion Therapy of Ureteral Stones
NCT02563405	PHASE2/PHASE3	UNKNOWN	The Effects of Doxazosin and Nifedipine on Blood Pressure Variability and Uric Acid in Plasma in Hypertensive Patients
NCT03176693	PHASE3	COMPLETED	Preoperative Alpha Blockade for Pheochromocytoma
NCT04135846	PHASE2	RECRUITING	Alpha-1 Blockade for Alcohol Use Disorder (AUD)
NCT00000522	PHASE2	COMPLETED	Treatment of Mild Hypertension Study (TOMHS)
NCT01145183	PHASE2	COMPLETED	Pharmacogenetics of Doxazosin for Cocaine Dependence
NCT01730846	PHASE2	COMPLETED	Does Doxazosin Attenuate Stress-induced Smoking and Improve Clinical Outcomes?
NCT01953432	PHASE2	COMPLETED	Pharmacogenetic Trial of Doxazosin for Treatment of Cocaine Abuse
NCT02500602	PHASE2	COMPLETED	CAP: Doxazosin in the Treatment of Co-Occurring PTSD and Alcohol Use Disorders
NCT02989493	PHASE2	COMPLETED	Testing Doxazosin to Treat Stress Mechanisms in Alcoholism
NCT05360953	PHASE2	SUSPENDED	Treating Nightmares in Posttraumatic Stress Disorder With Clonidine and Doxazosin
NCT00880997	PHASE1	COMPLETED	The Efficacy of Doxazosin for Cocaine Users
NCT01062945	PHASE1	COMPLETED	The Effects of Doxazosin on the Cardiovascular and Subjective Effects of Cocaine
NCT01100021	PHASE1	COMPLETED	Hemodynamic Study of Avanafil and Two α-Adrenergic Blockers,Doxazosin and Tamsulosin
NCT01386177	PHASE1	COMPLETED	Pharmacological Interaction Between Doxazosin and Methylenedioxymethamphetamine (MDMA)
NCT02266537	PHASE1	COMPLETED	Study to Assess the Influence of Three Different α-antagonists and Placebo on the Extent of Weekly Phenylephrine-induced Mydriasis at Three Different Concentrations of Phenylephrine in Healthy Male Volunteers
NCT02308202	PHASE1	COMPLETED	DOXAZOSIN FOR PTSD
NCT02538744	PHASE1	COMPLETED	Complementary Combination Therapy for Cocaine Dependence
NCT02785393	PHASE1	COMPLETED	DOX as a Potential Treatment for Methamphetamine Dependence
NCT01437046	EARLY_PHASE1	COMPLETED	Doxazosin an a1 Antagonist for Alcohol Dependence
NCT00006294	Not specified	COMPLETED	Genetics of Hypertension Associated Treatments (GenHAT)
NCT00424801	Not specified	TERMINATED	Effects of Intensive Long-Term Vasodilation in Hypertensive Patients With Microvascular Angina Pectoris
NCT00730418	Not specified	COMPLETED	Effects of Chronic Use of Doxazosin in Men With Benign Prostatic Hyperplasia

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 5 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.

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

Molecule	Source	Status	Shared targets
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
ALFUZOSIN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
AMLODIPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
APRACLONIDINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
ASENAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
ATENOLOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
AZELASTINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
BRIMONIDINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
BUSPIRONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
CARIPRAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
CISAPRIDE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
CLONIDINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
CLOZAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
DEXMEDETOMIDINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
DOPAMINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
EBASTINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
EPINEPHRINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
FENOLDOPAM	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
HALOPERIDOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
INDACATEROL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
INDORAMIN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
ISOPROTERENOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
LABETALOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
MOXISYLYTE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
NAFTOPIDIL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
NEFAZODONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
NOREPINEPHRINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
OLANZAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
OXYMETAZOLINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
PHENTOLAMINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
PRAZOSIN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
QUETIAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
RISPERIDONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
SERTINDOLE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
SILODOSIN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
TAMSULOSIN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
TEGASEROD	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
TERAZOSIN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
TERFENADINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
TOLAZOLINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
VERAPAMIL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
VILAZODONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
XYLOMETAZOLINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
ZIPRASIDONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
BUNAZOSIN	ChEMBL	Phase 3	ADRA1A, ADRA1B, ADRA1D
IDAZOXAN	ChEMBL	Phase 3	ADRA1A, ADRA1B, ADRA1D
LATREPIRDINE	ChEMBL	Phase 3	ADRA1A, ADRA1B, ADRA1D
MEDETOMIDINE	ChEMBL	Phase 3	ADRA1A, ADRA1B, ADRA1D
YOHIMBINE	ChEMBL	Phase 3	ADRA1A, ADRA1B, ADRA1D
ABANOQUIL	ChEMBL	Phase 2	ADRA1A, ADRA1B, ADRA1D
CIRAZOLINE	ChEMBL	Phase 2	ADRA1A, ADRA1B, ADRA1D
DEXNIGULDIPINE	ChEMBL	Phase 2	ADRA1A, ADRA1B, ADRA1D
IPSAPIRONE	ChEMBL	Phase 2	ADRA1A, ADRA1B, ADRA1D
MAZAPERTINE	ChEMBL	Phase 2	ADRA1A, ADRA1B, ADRA1D
NIGULDIPINE	ChEMBL	Phase 2	ADRA1A, ADRA1B, ADRA1D
PIPEROXAN	ChEMBL	Phase 2	ADRA1A, ADRA1B, ADRA1D
PIZOTYLINE	ChEMBL	Phase 2	ADRA1A, ADRA1B, ADRA1D
SPIRAMIDE	ChEMBL	Phase 2	ADRA1A, ADRA1B, ADRA1D