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Nebivolol

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Also known as HypolocNarbivololNebiletNebivolol component of byvalsonR-65824R65,824NEBIVOLOL.HCL

Summary

Nebivolol (CHEMBL434394) is an approved small molecule (ATC C07AB12) targeting ADRB1, ADRB2, and ADRB3; indicated across 8 conditions including cardiovascular disorder and hypertensive disorder.

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: C07AB12
  • Targets: 3 (ADRB1, ADRB2, ADRB3)
  • Indications: 8 conditions
  • Clinical trials: 93
  • Chemistry: 405.4 Da · C22H25F2NO4

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL434394
NameNebivolol
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID71301
ChEBICHEBI:64019
ATCC07AB12
Molecular formulaC22H25F2NO4
Molecular weight405.4
InChIKeyKOHIRBRYDXPAMZ-UHFFFAOYSA-N

SMILES: C1CC2=C(C=CC(=C2)F)OC1C(CNCC(C3CCC4=C(O3)C=CC(=C4)F)O)O

IUPAC name: 1-(6-fluoro-3,4-dihydro-2H-chromen-2-yl)-2-[[2-(6-fluoro-3,4-dihydro-2H-chromen-2-yl)-2-hydroxyethyl]amino]ethanol

ChEBI definition: A member of the class of chromanes that is 2,2’-iminodiethanol in which one hydrogen attached to each hydroxy-bearing carbon is replaced by a 6-fluorochroman-2-yl group.

Also known as: Hypoloc, Narbivolol, Nebilet, Nebivolol, Nebivolol component of byvalson, R-65824, R65,824, nebivolol, NEBIVOLOL, NEBIVOLOL.HCL

Parent form; salt/anhydrous children: CHEMBL1201731

Patent coverage: 2,483 distinct patent families (9,645 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 9,539 (99%) 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).

GeneTargetActionpAffinityCancer dependencyUniProt
ADRB1β1-adrenoceptorAntagonist9.20%P08588
ADRB2β2-adrenoceptorAntagonist80.4%P07550
ADRB3β3-adrenoceptorAntagonist70.1%P13945

Broader ChEMBL bioactivity targets: 32 (assay-derived). Sample: Vasopressin V2 receptor, 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Alpha-2C adrenergic receptor, Voltage-dependent L-type calcium channel subunit alpha-1C, Alpha-2B adrenergic receptor, A-type voltage-gated potassium channel KCND3, Sodium channel protein type 5 subunit alpha, Beta-2 adrenergic receptor, Beta-1 adrenergic receptor.

Bioactivity

ChEMBL activities: 25 potent at pChembl ≥ 5 of 38 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
ADRB18.52AC503nMCHEMBL_ACT_25122024
ADRB27.16AC5070nMCHEMBL_ACT_25123073
HTR1A6.85AC50140nMCHEMBL_ACT_25164584
KCNH26.5IC50316.2nMCHEMBL_ACT_15258089
SLC6A46.12AC50750nMCHEMBL_ACT_25150580
KCNH26.08AC50830nMCHEMBL_ACT_25118227
SLC6A25.82AC501500nMCHEMBL_ACT_25145249
HTR1A5.8AC501600nMCHEMBL_ACT_25217263
ADRA2C5.7AC502000nMCHEMBL_ACT_25148134
DRD35.7AC502000nMCHEMBL_ACT_25193779
ADRA1A5.51AC503100nMCHEMBL_ACT_25218252
SLC6A35.5AC503200nMCHEMBL_ACT_25124200
OPRM15.48AC503300nMCHEMBL_ACT_25147071
DRD25.46AC503500nMCHEMBL_ACT_25140589
ADRA2B5.35AC504500nMCHEMBL_ACT_25143952
GHSR5.34AC504600nMCHEMBL_ACT_25172998
KCNH25.2IC506310nMCHEMBL_ACT_15258029
KCNH25.2IC506310nMCHEMBL_ACT_15258059
SCN5A5.2IC506310nMCHEMBL_ACT_15258183
HTR2A5.15AC507100nMCHEMBL_ACT_25225405
SCN5A5.1IC507943nMCHEMBL_ACT_15258213
ADRA2A5.09AC508100nMCHEMBL_ACT_25220136
MC3R5.06AC508700nMCHEMBL_ACT_25183647
HTR2B5.06AC508800nMCHEMBL_ACT_25227766
OPRK15AC5010000nMCHEMBL_ACT_25129663

Target pathways

Aggregated over 3 target gene(s): ADRB1, ADRB2, ADRB3.

Top Reactome pathways

16 total, by targets touching each:

PathwayTargetsGenes
Signal Transduction3ADRB1, ADRB2, ADRB3
Signaling by GPCR3ADRB1, ADRB2, ADRB3
Class A/1 (Rhodopsin-like receptors)3ADRB1, ADRB2, ADRB3
Amine ligand-binding receptors3ADRB1, ADRB2, ADRB3
GPCR downstream signalling3ADRB1, ADRB2, ADRB3
Adrenoceptors3ADRB1, ADRB2, ADRB3
G alpha (s) signalling events3ADRB1, ADRB2, ADRB3
GPCR ligand binding3ADRB1, ADRB2, ADRB3
Membrane Trafficking1ADRB2
Metabolism of proteins1ADRB2
Vesicle-mediated transport1ADRB2
Deubiquitination1ADRB2
Ub-specific processing proteases1ADRB2
Post-translational protein modification1ADRB2
Cargo recognition for clathrin-mediated endocytosis1ADRB2
Clathrin-mediated endocytosis1ADRB2

Dominant GO biological processes

GO termTargets
diet induced thermogenesis3
norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure3
adenylate cyclase-activating G protein-coupled receptor signaling pathway3
response to cold3
heat generation3
negative regulation of multicellular organism growth3
positive regulation of MAPK cascade3
brown fat cell differentiation3
adenylate cyclase-activating adrenergic receptor signaling pathway3
positive regulation of cold-induced thermogenesis3
signal transduction3
G protein-coupled receptor signaling pathway3
positive regulation of cardiac muscle cell apoptotic process2
adenylate cyclase-modulating G protein-coupled receptor signaling pathway2
negative regulation of smooth muscle contraction2

Indications & clinical

Indications

8 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).

IndicationTrial phaseMONDOEFO
cardiovascular disorder4MONDO:0004995EFO:0000319
hypertensive disorder3MONDO:0005044EFO:0000537
severe acute respiratory syndrome3MONDO:0005091MONDO:0100096
Marfan syndrome3MONDO:0007947MONDO:0007947
stroke disorder2MONDO:0005098EFO:0000712
essential hypertension2MONDO:0001134MONDO:0001134
idiopathic pulmonary fibrosis1MONDO:0800504EFO:0000768
osteoporosis0MONDO:0005298EFO:0003882

Clinical trials

Total trials: 93.

Phase distribution

PhaseTrials
PHASE444
PHASE317
Not specified16
PHASE26
PHASE2/PHASE34
PHASE14
EARLY_PHASE12

Top trials by phase / activity

NCTPhaseStatusTitle
NCT03778554PHASE4ACTIVE_NOT_RECRUITINGDanish Trial of Beta Blocker Treatment After Myocardial Infarction Without Reduced Ejection Fraction
NCT06249802PHASE4NOT_YET_RECRUITINGBeta-blockade in Unruptured Intracranial Aneurysm
NCT00517725PHASE4COMPLETEDNebivolol Versus Bisoprolol Versus Carvedilol in Heart Failure
NCT00673075PHASE4COMPLETEDThe Effect of Nebivolol in Hypertensive Patients With Coronary Artery Disease
NCT00734630PHASE4COMPLETEDEfficacy and Safety of Nebivolol (Added to Lisinopril or Losartan) in Hypertensive Patients
NCT00744237PHASE4COMPLETEDStudy of the Glycemic Effects of Nebivolol Compared With Metoprolol and HCTZ in Diabetic Hypertensive Patients
NCT00770861PHASE4COMPLETEDA Study on the Efficacy and Safety of Nebivolol Monotherapy in Hispanic Hypertensive Patients
NCT00775671PHASE4COMPLETEDComparative Effect of Nebivolol vs. Metoprolol on Insulin Sensitivity and Fibrinolytic Balance in Metabolic Syndrome
NCT00785512PHASE4COMPLETEDA Study on the Long-term Efficacy of Nebivolol After Withdrawal of Therapy
NCT00893984PHASE4TERMINATEDAlternative in Beta Blocker Intolerance: The ABBI Trial
NCT00924833PHASE4COMPLETEDEffects of Nebivolol Versus Carvedilol on Cardiopulmonary Function at High Altitude in Healthy Subjects.
NCT00992056PHASE4COMPLETEDNebivolol Versus Metoprolol: Sodium Sensitivity
NCT00999102PHASE4COMPLETEDNebivolol Versus Metoprolol: Comparative Effects on Fatigue and Quality of Life
NCT01041287PHASE4COMPLETEDEffect of Nebivolol on Oxidative Stress and Endothelial Progenitor Cells
NCT01049009PHASE4COMPLETEDThe Effect of Nebivolol on Endothelial Dysfunction in African Americans With Hypertension
NCT01057251PHASE4COMPLETEDNebivolol in Patients With Systolic Stage 2 Hypertension
NCT01157234PHASE4COMPLETEDNebivolol Effect on Nitric Oxide Levels, Blood Pressure, and Renal Function in Kidney Transplant Patients
NCT01202175PHASE4COMPLETEDEffects of the Beta-blocker Nebivolol (Bystolic) on Subjects With High Normal Blood Pressure and/or a Family History of Hypertension
NCT01206439PHASE4TERMINATEDAn Advanced Echocardiographic Evaluation of Nebivolol
NCT01218100PHASE4COMPLETEDEfficacy and Safety Study to Evaluate Combination Therapy With Nebivolol and Lisinopril vs. Placebo and Monotherapy in Patients With Stage 2 Diastolic Hypertension
NCT01230892PHASE4COMPLETEDEvaluation of The Effects of Nebivolol in Comparison to Atenolol on Wall Shear Stress and Rupture Prone Coronary Plaques
NCT01248338PHASE4COMPLETEDEffects of Nebivolol Versus Metoprolol Succinate on Endothelial Function
NCT01395329PHASE4COMPLETEDNebivolol and the Endothelin (ET)-1 System
NCT01415531PHASE4COMPLETEDStudy of the Efficacy and Safety of Nebivolol in Younger Patients (18 - 54 Years)
NCT01501929PHASE4COMPLETEDEffects of Nebivolol on Skeletal Muscle During Exercise in Hypertensive Patients
NCT01502787PHASE4COMPLETEDComparison of Nebivolol and Metoprolol With Exercise and Angiotensin II in Hypertensive Patients
NCT01595516PHASE4COMPLETEDNebivolol and Endothelial Regulation of Fibrinolysis (NERF)
NCT01605370PHASE4TERMINATEDCan Nebivolol Reverse Inappropriate Left Ventricular Mass in Hypertensive Patients?
NCT01665508PHASE4COMPLETEDStudy to Evaluate Effect of Nebivolol on Angina in Women With Microvascular Disease
NCT01771406PHASE4UNKNOWNCPAP and Nebivolol in Hypertensive Obstructive Sleep Apnea (OSA) Patients.
NCT01885988PHASE4UNKNOWNNebivolol Effects on Endothelial Function and Erectile Function
NCT01920282PHASE4COMPLETEDNebivolol, Lifestyle Modification and Arterial Stiffness
NCT01961323PHASE4COMPLETEDEffect of Nebivolol on the Blood Flow in Hearts of Adults With High Blood Pressure and Abnormal Filling of Heart
NCT02053246PHASE4TERMINATEDImproving Treatment Personalization of Pulmonary Hypertension Associated With Diastolic Heart Failure
NCT02057328PHASE4UNKNOWNComparative Study of the Effects of Telmisartan and Nebivolol
NCT02710071PHASE4COMPLETEDTreatment of OSA Associated Hypertension With Nebivolol or Hydrochlorothiazide
NCT03245996PHASE4COMPLETEDThe Impact of Heart Rate on Central Blood Pressure in Sick Sinus Syndrome Patients With a Permanent Cardiac Pacemaker
NCT03930433PHASE4COMPLETEDThe Effect of Nebivolol in Hypertensive Patients With Coronary Arterial Spasm
NCT04845061PHASE4UNKNOWNEvaluating the Outcome of Cardio Selective beta1- Blockers Use in Patients With Copd
NCT05257148PHASE4COMPLETEDEffectiveness and Safety of Combination of Nebivolol and Zofenopril in Hypertensive patIents Versus Each Monotherapy

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):

GuidelineSourceGene(s)DosingRecommendation
Annotation of CPIC Guideline for acebutolol, betaxolol, bisoprolol, caCPICCYP2D6
Annotation of CPIC Guideline for acebutolol, atenolol, betaxolol, bisoCPICADRA2C;ADRB1;GRK4;GRK5

PharmGKB also curates 0 clinical and 3 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

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

MoleculeSourceStatusShared targets
CrizotinibChEMBL + PubChemPhase 4 (approved)ADRB1, ADRB2, ADRB3
DesloratadineChEMBL + PubChemPhase 4 (approved)ADRB1, ADRB2, ADRB3
DihydroergotamineChEMBL + PubChemPhase 4 (approved)ADRB1, ADRB2, ADRB3
PramipexoleChEMBL + PubChemPhase 4 (approved)ADRB1, ADRB2, ADRB3
RIFAMPINChEMBL + PubChemPhase 4 (approved)ADRB1, ADRB2, ADRB3
TEGASERODChEMBL + PubChemPhase 4 (approved)ADRB1, ADRB2, ADRB3
ARIPIPRAZOLEChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
BISOPROLOLChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
BROMOCRIPTINEChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
CARVEDILOLChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
CLOTRIMAZOLEChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
EPINEPHRINEChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
FENOTEROLChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
FORMOTEROLChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
ISOPROTERENOLChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
LABETALOLChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
LEVOBUNOLOLChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
MONTELUKASTChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
NOREPINEPHRINEChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
PHENYLEPHRINEChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
PIMOZIDEChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
PINDOLOLChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
PRACTOLOLChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
PROPAFENONEChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
PROPRANOLOLChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
SALMETEROLChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
SOTALOLChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
TAMOXIFENChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
THIORIDAZINEChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
TIMOLOLChEMBLPhase 4 (approved)ADRB1, ADRB2, ADRB3
ALPRENOLOLChEMBLPhase 2ADRB1, ADRB2, ADRB3
BOPINDOLOLChEMBLPhase 2ADRB1, ADRB2, ADRB3
CIMATEROLChEMBLPhase 2ADRB1, ADRB2, ADRB3
FLESTOLOLChEMBLPhase 2ADRB1, ADRB2, ADRB3
LEVISOPRENALINEChEMBLPhase 2ADRB1, ADRB2, ADRB3
LEVOPROPRANOLOLChEMBLPhase 2ADRB1, ADRB2, ADRB3
MILVETEROLChEMBLPhase 2ADRB1, ADRB2, ADRB3
RAFABEGRONChEMBLPhase 2ADRB1, ADRB2, ADRB3
SOLABEGRONChEMBLPhase 2ADRB1, ADRB2, ADRB3
TRETOQUINOLChEMBLPhase 2ADRB1, ADRB2, ADRB3
XAMOTEROLChEMBLPhase 2ADRB1, ADRB2, ADRB3
ZENIDOLOLChEMBLPhase 2ADRB1, ADRB2, ADRB3
AlogliptinPubChemApprovedADRB1, ADRB2, ADRB3
BosentanPubChemApprovedADRB1, ADRB2, ADRB3
FidaxomicinPubChemApprovedADRB1, ADRB2, ADRB3
GlycopyrrolatePubChemApprovedADRB1, ADRB2, ADRB3
LinagliptinPubChemApprovedADRB1, ADRB2, ADRB3
MethotrexatePubChemApprovedADRB1, ADRB2, ADRB3
PropoxyphenePubChemApprovedADRB1, ADRB2, ADRB3
PyrazinamidePubChemApprovedADRB1, ADRB2, ADRB3
Tiotropium Bromide MonohydratePubChemApprovedADRB1, ADRB2, ADRB3
CLOZAPINEChEMBL + PubChemPhase 4 (approved)ADRB2, ADRB3
OLANZAPINEChEMBL + PubChemPhase 4 (approved)ADRB2, ADRB3
OLODATEROLChEMBL + PubChemPhase 4 (approved)ADRB1, ADRB2
TAMSULOSINChEMBL + PubChemPhase 4 (approved)ADRB1, ADRB2
ACEBUTOLOLChEMBLPhase 4 (approved)ADRB1, ADRB2
ALBUTEROLChEMBLPhase 4 (approved)ADRB1, ADRB2
AMIODARONEChEMBLPhase 4 (approved)ADRB1, ADRB3
AMITRIPTYLINEChEMBLPhase 4 (approved)ADRB1, ADRB2
AMLODIPINEChEMBLPhase 4 (approved)ADRB2, ADRB3

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot