Labetalol

Summary

Labetalol (CHEMBL429) is an approved small molecule (ATC C07AG01) targeting ADRA1A, ADRA1D, and ADRB1; indicated across 10 conditions including cardiovascular disorder and hypertensive disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C07AG01
• Targets: 4 (ADRA1A, ADRA1D, ADRB1…)
• Indications: 10 conditions
• Clinical trials: 50
• Chemistry: 328.4 Da · C19H24N2O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL429
Name	Labetalol
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	3869
ChEBI	CHEBI:167638
ATC	C07AG01
Molecular formula	C19H24N2O3
Molecular weight	328.4
InChIKey	SGUAFYQXFOLMHL-UHFFFAOYSA-N

SMILES: CC(CCC1=CC=CC=C1)NCC(C2=CC(=C(C=C2)O)C(=O)N)O

IUPAC name: 2-hydroxy-5-[1-hydroxy-2-(4-phenylbutan-2-ylamino)ethyl]benzamide

ChEBI definition: A member of the class of benzamides that is benzamide substituted by a hydroxy group at position 2 and by a 1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl group at position 5.

Also known as: AH-5158A FREE BASE, Ibidomide, Labetalol, Normozide, SCH-15719W FREE BASE, SID90341718, labetalol, LABETALOL

Parent form; salt/anhydrous children: CHEMBL1200323

Patent coverage: 5,967 distinct patent families (23,037 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 23,033 (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	7.3		P35348
ADRA1D	α1D-adrenoceptor	Antagonist	6.6	0.2%	P25100
ADRB1	β1-adrenoceptor	Antagonist	8.2	0%	P08588
ADRB2	β2-adrenoceptor	Partial agonist	7.96	0.4%	P07550

Broader ChEMBL bioactivity targets: 18 (assay-derived). Sample: 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Adrenergic receptor alpha-1, Beta-2 adrenergic receptor, Beta-1 adrenergic receptor, 5-hydroxytryptamine receptor 1A, Sodium-dependent noradrenaline transporter, Alpha-1D adrenergic receptor, Sodium-dependent serotonin transporter, Mu-type opioid receptor.

Bioactivity

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

Target	pChembl	Type	Value	Unit	Activity ID
ADRB1	8.23	Ki	5.84	nM	CHEMBL_ACT_7767767
ADRB1	8	IC50	10	nM	CHEMBL_ACT_7767766
ADRB2	7.96	Ki	11	nM	CHEMBL_ACT_7767769
ADRB2	7.8	IC50	16	nM	CHEMBL_ACT_7767768
P43140	7.64	Ki	23	nM	CHEMBL_ACT_7767755
Q8K4Z4	7.4	Kd	39.81	nM	CHEMBL_ACT_261200
P43140	7.24	IC50	57	nM	CHEMBL_ACT_7767754
HTR1A	6.98	AC50	104	nM	CHEMBL_ACT_25165053
ADRA1D	6.8	Kd	158.5	nM	CHEMBL_ACT_261201
P19327	6.65	Ki	225	nM	CHEMBL_ACT_7769982
ADRA1D	6.59	Ki	256	nM	CHEMBL_ACT_7767759
P15823	6.49	Ki	323	nM	CHEMBL_ACT_7767757
P19327	6.41	IC50	393	nM	CHEMBL_ACT_7769981
ADRA1D	6.28	IC50	521	nM	CHEMBL_ACT_7767758
P15823	6.23	IC50	583	nM	CHEMBL_ACT_7767756
SIGMAR1	6.12	Ki	763	nM	CHEMBL_ACT_7771996
CYP2D6	6.1	IC50	800	nM	CHEMBL_ACT_7767822
SLC6A3	5.89	Ki	1277	nM	CHEMBL_ACT_7767837
SLC6A3	5.79	IC50	1607	nM	CHEMBL_ACT_7767836
SIGMAR1	5.74	IC50	1815	nM	CHEMBL_ACT_7771995
HTR2B	5.71	Ki	1933	nM	CHEMBL_ACT_7769988
SLC6A3	5.65	AC50	2224	nM	CHEMBL_ACT_25124988
OPRM1	5.62	AC50	2422	nM	CHEMBL_ACT_25158204
HTR2B	5.52	IC50	3037	nM	CHEMBL_ACT_7769987
SLC6A2	5.48	Ki	3326	nM	CHEMBL_ACT_7767773
SLC6A2	5.47	IC50	3354	nM	CHEMBL_ACT_7767772
SLC6A2	5.39	AC50	4045	nM	CHEMBL_ACT_25146029
DRD3	5.23	AC50	5849	nM	CHEMBL_ACT_25194551

Target pathways

Aggregated over 4 target gene(s): ADRA1A, ADRA1D, ADRB1, ADRB2.

Top Reactome pathways

18 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	4	ADRA1A, ADRA1D, ADRB1, ADRB2
Signaling by GPCR	4	ADRA1A, ADRA1D, ADRB1, ADRB2
Class A/1 (Rhodopsin-like receptors)	4	ADRA1A, ADRA1D, ADRB1, ADRB2
Amine ligand-binding receptors	4	ADRA1A, ADRA1D, ADRB1, ADRB2
GPCR downstream signalling	4	ADRA1A, ADRA1D, ADRB1, ADRB2
Adrenoceptors	4	ADRA1A, ADRA1D, ADRB1, ADRB2
GPCR ligand binding	4	ADRA1A, ADRA1D, ADRB1, ADRB2
G alpha (q) signalling events	2	ADRA1A, ADRA1D
G alpha (12/13) signalling events	2	ADRA1A, ADRA1D
G alpha (s) signalling events	2	ADRB1, ADRB2
Membrane Trafficking	1	ADRB2
Metabolism of proteins	1	ADRB2
Vesicle-mediated transport	1	ADRB2
Deubiquitination	1	ADRB2
Ub-specific processing proteases	1	ADRB2
Post-translational protein modification	1	ADRB2
Cargo recognition for clathrin-mediated endocytosis	1	ADRB2
Clathrin-mediated endocytosis	1	ADRB2

Dominant GO biological processes

GO term	Targets
signal transduction	4
G protein-coupled receptor signaling pathway	4
positive regulation of MAPK cascade	4
adenylate cyclase-activating adrenergic receptor signaling pathway	4
adrenergic receptor signaling pathway	3
positive regulation of heart rate by epinephrine-norepinephrine	2
positive regulation of the force of heart contraction by epinephrine-norepinephrine	2
smooth muscle contraction	2
phospholipase C-activating G protein-coupled receptor signaling pathway	2
positive regulation of cytosolic calcium ion concentration	2
cell-cell signaling	2
positive regulation of vasoconstriction	2
neuron-glial cell signaling	2
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	2
diet induced thermogenesis	2

Indications & clinical

Indications

10 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
cardiovascular disorder	4	MONDO:0004995	EFO:0000319
hypertensive disorder	3	MONDO:0005044	EFO:0000537
preeclampsia	3	MONDO:0005081	EFO:0000668
stroke disorder	2	MONDO:0005098	EFO:0000712
cocaine dependence	2	MONDO:0005186	EFO:0002610
nicotine dependence	2	MONDO:0008575	EFO:0003768
intracerebral hemorrhage	2	MONDO:0013792	EFO:0005669
sinusitis	2	MONDO:0005961	EFO:0007486
hypotensive disorder	0	MONDO:0005468	EFO:0005251

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

Clinical trials

Total trials: 50.

Phase distribution

Phase	Trials
PHASE4	14
Not specified	14
PHASE2	11
PHASE3	5
PHASE1/PHASE2	3
EARLY_PHASE1	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05309460	PHASE4	RECRUITING	Labetalol or Nifedipine for Control of Postpartum Hypertension: A Randomized Controlled Trial
NCT06915792	PHASE4	NOT_YET_RECRUITING	PEACE Trial: Postpartum Evaluation of Antihypertensive Cessation and Efficacy
NCT07034898	PHASE4	ENROLLING_BY_INVITATION	Dexmedetomidine vs Labetalol for Airway Stress in Hypertensive Craniotomy Patients
NCT00765648	PHASE4	COMPLETED	Evaluation of Intravenous Cardene(Nicardipine)and Labetalol Use in the Emergency Department
NCT01114971	PHASE4	COMPLETED	Labetalol and Esmolol: Vital Signs and Post Operative Pain Management
NCT01912677	PHASE4	COMPLETED	Oral Antihypertensive Regimens for Management of Hypertension in Pregnancy
NCT02531490	PHASE4	UNKNOWN	Early Vascular Adjustments During Hypertensive Pregnancy
NCT03506724	PHASE4	COMPLETED	Response to Anti-hypertensives in Pregnant and Postpartum Patients
NCT03809065	PHASE4	COMPLETED	Effects of Nitroglycerin Versus Labetalol on Tissue Perfusion During Deliberate Hypotension
NCT04343235	PHASE4	TERMINATED	Postpartum Management of Gestational Hypertensive Disorders Using Furosemide
NCT05139238	PHASE4	TERMINATED	Postpartum Hypertension Study
NCT05368376	PHASE4	COMPLETED	Is Labetalol More Effective Than Metoprolol for Controlled Hypotensive Anesthesia During Endoscopic Nasal Surgeries?
NCT06093893	PHASE4	COMPLETED	Hypotensive Anesthesia for Orthognathic Surgery
NCT07277283	PHASE4	COMPLETED	Nicardipine vs. Labetalol
NCT04298034	PHASE3	ACTIVE_NOT_RECRUITING	Preeclampsia Postpartum Antihypertensive Treatment
NCT05551104	PHASE3	RECRUITING	Safest Choice of Antihypertensive Regimen for Postpartum Hypertension
NCT06677970	PHASE3	RECRUITING	Outcome in Patients Treated With Endovascular Thrombectomy - optIMAL Blood Pressure Control 2 (OPTIMAL-BP 2)
NCT01538875	PHASE3	COMPLETED	Hydralazine Versus Labetalol for the Management of Hypertensive Disorders of Pregnancy
NCT02426177	PHASE3	UNKNOWN	Comparison of Tab.Labetalol and Tab.Nifedipine for Management of Postpartum Hypertension
NCT03325348	PHASE2/PHASE3	UNKNOWN	Oral Nifedipine Versus IV Labetalol in Severe Pre Eclampsia
NCT00000291	PHASE2	COMPLETED	Effects of Labetalol on Human Cocaine Use - 8
NCT00000297	PHASE2	COMPLETED	Effects of Labetalol on Nicotine Administration in Humans - 14
NCT00194974	PHASE1/PHASE2	WITHDRAWN	Treatment Targets for Chronic Hypertension in Pregnancy
NCT00963976	PHASE2	COMPLETED	Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial
NCT01408524	PHASE1/PHASE2	COMPLETED	Control of Emergence Blood Pressure During Craniotomy for Tumor Surgery Between Labetolol and Diltiazem
NCT02050529	PHASE2	COMPLETED	Randomized Controlled Trial of Labetalol Versus Hydralazine for Severe Hypertension in Obstetric Patients.
NCT02281838	PHASE2	TERMINATED	The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial II
NCT02327793	PHASE2	COMPLETED	Perfusion and Antihypertensive Therapy in Acute Ischemic Stroke
NCT02997800	PHASE2	COMPLETED	The Effect of Intraoperative Labetalol on Time to Discharge
NCT03661346	PHASE2	COMPLETED	Esmolol vs. Labetalol in Endoscopic Sinus Surgery
NCT04116112	PHASE2	COMPLETED	Blood Pressure After Endovascular Stroke Therapy-II
NCT04484350	PHASE2	COMPLETED	Blood Pressure Management in Stroke Following Endovascular Treatment
NCT05955040	PHASE2	TERMINATED	Treatment of Elevated Blood Pressures in Early Pregnancy
NCT06360601	PHASE1/PHASE2	UNKNOWN	Intravenous Labetalol Versus Hydralazine in Preeclampsia
NCT03059316	EARLY_PHASE1	COMPLETED	Effect of Hypotensive Anesthesia on the Perfusion Index
NCT03105661	EARLY_PHASE1	UNKNOWN	Use of Impedance Cardiography to Decrease the Risk of Pre-eclampsia in Obese Patients
NCT03511118	Not specified	RECRUITING	Pharmacokinetics and Safety of Commonly Used Drugs in Lactating Women and Breastfed Infants
NCT04755764	Not specified	RECRUITING	Effect of Labetalol, Atenolol, and Nifedipine on Maternal Hemodynamics Measured by ICG in Early Pregnancy
NCT07192081	Not specified	RECRUITING	Comparative Efficacy of Intravenous Labetalol and Lignocaine in Mitigating Hemodynamic Responses to Laryngoscopy During Laparoscopic Cholecystectomy
NCT07363343	Not specified	NOT_YET_RECRUITING	Nifedipine and Enalapril vs Nifedipine and Labetalol for the Treatment of Postpartum Hypertension Study

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (2) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

Guideline	Source	Gene(s)	Dosing	Recommendation
Annotation of CPIC Guideline for acebutolol, atenolol, betaxolol, biso	CPIC	ADRA2C;ADRB1;GRK4;GRK5
Annotation of CPIC Guideline for carvedilol, labetalol, nadolol, pindo	CPIC	ADRB2

PharmGKB also curates 0 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.

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

Molecule	Source	Status	Shared targets
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1, ADRB2
PRAMIPEXOLE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1, ADRB2
TAMSULOSIN	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1, ADRB2
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1, ADRB2
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1, ADRB2
ATENOLOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1, ADRB2
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1, ADRB2
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1, ADRB2
CARVEDILOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1, ADRB2
CLEMASTINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1, ADRB2
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1, ADRB2
DOBUTAMINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1, ADRB2
DOMPERIDONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1, ADRB2
EPINEPHRINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1, ADRB2
ERGOTAMINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1, ADRB2
INDACATEROL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1, ADRB2
ISOPROTERENOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1, ADRB2
NOREPINEPHRINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1, ADRB2
NORTRIPTYLINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1, ADRB2
SALMETEROL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1, ADRB2
TEGASEROD	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1, ADRB2
THIORIDAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1, ADRB2
LISURIDE	ChEMBL	Phase 3	ADRA1A, ADRA1D, ADRB1, ADRB2
SPIRAMIDE	ChEMBL	Phase 2	ADRA1A, ADRA1D, ADRB1, ADRB2
ACLIDINIUM BROMIDE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRB1, ADRB2
CHENODIOL	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRB1, ADRB2
CLOFARABINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRB1, ADRB2
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRB1, ADRB2
DESLORATADINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRB1, ADRB2
OLODATEROL	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRB1, ADRB2
PROPOXYPHENE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRB1, ADRB2
PYRAZINAMIDE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRB1, ADRB2
AMLODIPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB2
AMOXAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB2
ARFORMOTEROL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRB1, ADRB2
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1
AZELASTINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1
BENPERIDOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRB1, ADRB2
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRB1, ADRB2
CARIPRAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRB1, ADRB2
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	ADRA1D, ADRB1, ADRB2
CLOZAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB2
DARIFENACIN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRB1, ADRB2
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1
DOPAMINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB2
DOXAZOSIN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB2
EBASTINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1
FENOTEROL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRB1, ADRB2
FLUSPIRILENE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRB1, ADRB2
HALOPERIDOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB2
METOPROLOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRB1, ADRB2
NADOLOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRB1, ADRB2
NAFTOPIDIL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB1
NEBIVOLOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRB1, ADRB2
NITAZOXANIDE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRB1, ADRB2
OLANZAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, ADRB2
OXPRENOLOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRB1, ADRB2
PHENYLEPHRINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRB1, ADRB2
PIMOZIDE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRB1, ADRB2