Guanfacine

Summary

Guanfacine (CHEMBL862) is an approved small molecule (ATC C02AC02) targeting ADRA2A, ADRA2B, and ADRA2C; indicated across 17 conditions including hypertensive disorder and tourette syndrome.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C02AC02
• Targets: 3 (ADRA2A, ADRA2B, ADRA2C)
• Indications: 17 conditions
• Clinical trials: 46
• Chemistry: 246.09 Da · C9H9Cl2N3O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL862
Name	Guanfacine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	3519
ATC	C02AC02
Molecular formula	C9H9Cl2N3O
Molecular weight	246.09
InChIKey	INJOMKTZOLKMBF-UHFFFAOYSA-N

SMILES: C1=CC(=C(C(=C1)Cl)CC(=O)N=C(N)N)Cl

IUPAC name: N-(diaminomethylidene)-2-(2,6-dichlorophenyl)acetamide

Also known as: Guanfacina, Guanfacine, Intuniv, NSC-759121, SID11111221, SID11111222, SID11113866, SID26752038, SID90341397, SID104171166, guanfacine, SID124880211

Parent form; salt/anhydrous children: CHEMBL1200494

Patent coverage: 5,892 distinct patent families (23,781 SureChEMBL compound mentions), from 2 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
ADRA2A	α2A-adrenoceptor	Agonist	6.5	0.1%	P08913
ADRA2B	α2B-adrenoceptor	Full agonist	7.6	0.2%	P18089
ADRA2C	α2C-adrenoceptor	Agonist	7.2	0%	P18825

Broader ChEMBL bioactivity targets: 25 (assay-derived). Sample: Prelamin-A/C, 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Alpha-2C adrenergic receptor, Alpha-2B adrenergic receptor, Amine oxidase [flavin-containing] A, Menin/Histone-lysine N-methyltransferase MLL, 5-hydroxytryptamine receptor 1A, Alpha-1D adrenergic receptor, 5-hydroxytryptamine receptor 2A.

Bioactivity

ChEMBL activities: 47 potent at pChembl ≥ 5 of 61 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
MAPK1	8.4	Potency	4	nM	CHEMBL_ACT_4524498
ADRA1A	8.03	AC50	9.3	nM	CHEMBL_ACT_25208506
P08482	7.9	Potency	12.6	nM	CHEMBL_ACT_4803461
NISCH	7.72	Ki	19.01	nM	CHEMBL_ACT_2564083
ADRA1A	7.61	AC50	24.5	nM	CHEMBL_ACT_25229650
ADRA2A	7.3	Ki	50	nM	CHEMBL_ACT_7662161
ADRA2A	7.28	EC50	52.48	nM	CHEMBL_ACT_25844356
ADRA2A	7.25	AC50	56.7	nM	CHEMBL_ACT_25220891
ADRA2A	6.96	AC50	110	nM	CHEMBL_ACT_25157069
ADRA2B	6.94	Ki	114	nM	CHEMBL_ACT_7662163
CYP2D6	6.9	Potency	125.9	nM	CHEMBL_ACT_4998279
CYP2D6	6.9	AC50	125.9	nM	CHEMBL_ACT_5988140
ADRA2A	6.87	IC50	134	nM	CHEMBL_ACT_7662160
CYP2C19	6.6	Potency	251.2	nM	CHEMBL_ACT_4020442
CYP2C19	6.6	AC50	251.2	nM	CHEMBL_ACT_6056545
ADRA2B	6.6	IC50	249	nM	CHEMBL_ACT_7662162
ADRA2B	6.54	EC50	288.4	nM	CHEMBL_ACT_25844359
HTR2B	6.45	AC50	358	nM	CHEMBL_ACT_25228518
LMNA	6.45	Potency	354.8	nM	CHEMBL_ACT_3625296
P43140	6.26	Ki	546	nM	CHEMBL_ACT_7662155
ADRA2C	6.22	EC50	602.6	nM	CHEMBL_ACT_25844362
HTR2A	6.21	AC50	610	nM	CHEMBL_ACT_25226146
HTR2C	6.12	Ki	761	nM	CHEMBL_ACT_7666389
HTR2A	6.07	Ki	861	nM	CHEMBL_ACT_7666385
ADRA2C	6.03	Ki	937	nM	CHEMBL_ACT_7662165
HTR2B	5.99	AC50	1013	nM	CHEMBL_ACT_25164291
HTR2B	5.88	Ki	1335	nM	CHEMBL_ACT_7666387
HTR2B	5.87	AC50	1342	nM	CHEMBL_ACT_25164054
P43140	5.87	IC50	1348	nM	CHEMBL_ACT_7662154
ADRA2A	5.86	AC50	1398	nM	CHEMBL_ACT_25155884

Target pathways

Aggregated over 3 target gene(s): ADRA2A, ADRA2B, ADRA2C.

Top Reactome pathways

19 total, by targets touching each:

Pathway	Targets	Genes
Hemostasis	3	ADRA2A, ADRA2B, ADRA2C
Signal Transduction	3	ADRA2A, ADRA2B, ADRA2C
Signaling by GPCR	3	ADRA2A, ADRA2B, ADRA2C
Class A/1 (Rhodopsin-like receptors)	3	ADRA2A, ADRA2B, ADRA2C
Amine ligand-binding receptors	3	ADRA2A, ADRA2B, ADRA2C
GPCR downstream signalling	3	ADRA2A, ADRA2B, ADRA2C
Adrenoceptors	3	ADRA2A, ADRA2B, ADRA2C
Adrenaline signalling through Alpha-2 adrenergic receptor	3	ADRA2A, ADRA2B, ADRA2C
G alpha (i) signalling events	3	ADRA2A, ADRA2B, ADRA2C
G alpha (z) signalling events	3	ADRA2A, ADRA2B, ADRA2C
GPCR ligand binding	3	ADRA2A, ADRA2B, ADRA2C
Platelet activation, signaling and aggregation	3	ADRA2A, ADRA2B, ADRA2C
Platelet Aggregation (Plug Formation)	3	ADRA2A, ADRA2B, ADRA2C
Metabolism	2	ADRA2A, ADRA2C
Integration of energy metabolism	2	ADRA2A, ADRA2C
Metabolism of proteins	2	ADRA2A, ADRA2C
Adrenaline,noradrenaline inhibits insulin secretion	2	ADRA2A, ADRA2C
Regulation of insulin secretion	2	ADRA2A, ADRA2C
Surfactant metabolism	2	ADRA2A, ADRA2C

Dominant GO biological processes

GO term	Targets
epidermal growth factor receptor signaling pathway	3
G protein-coupled receptor signaling pathway	3
negative regulation of norepinephrine secretion	3
regulation of vasoconstriction	3
platelet activation	3
negative regulation of epinephrine secretion	3
positive regulation of MAPK cascade	3
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	3
adrenergic receptor signaling pathway	3
adenylate cyclase-inhibiting adrenergic receptor signaling pathway	3
regulation of smooth muscle contraction	3
signal transduction	3
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	2
female pregnancy	2
negative regulation of insulin secretion	2

Indications & clinical

Indications

17 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
Tourette syndrome	3	MONDO:0007661	EFO:0004895
delirium	3	MONDO:0045057	EFO:0009267
Alzheimer disease	3	MONDO:0004975	MONDO:0004975
cocaine dependence	2	MONDO:0005186	EFO:0002610
stroke disorder	2	MONDO:0005098	EFO:0000712
attention deficit-hyperactivity disorder	2	MONDO:0007743	EFO:0003888
nicotine dependence	2	MONDO:0008575	EFO:0003768
drug dependence	2	MONDO:0005303	EFO:0003890
cannabis dependence	2	MONDO:0005689	EFO:0007191
trigeminal neuralgia	2	MONDO:0008599	EFO:1001219
schizotypal personality disorder	2	MONDO:0001087	MONDO:0001087
alcohol abuse	2	MONDO:0002046	MONDO:0007079
depressive disorder	2	MONDO:0002050	MONDO:0002050
post-traumatic stress disorder	1	MONDO:0005146	EFO:0001358

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

Clinical trials

Total trials: 46.

Phase distribution

Phase	Trials
PHASE4	14
PHASE2	12
Not specified	10
PHASE3	5
PHASE1	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07300956	PHASE4	NOT_YET_RECRUITING	Treating Young Children With Attention Deficit Hyperactivity Disorder
NCT00353379	PHASE4	TERMINATED	Pharmacology of Cognition in Schizotypal Personality Disorder
NCT00429273	PHASE4	COMPLETED	Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder
NCT00469664	PHASE4	UNKNOWN	Guanfacine Adjunctive Treatment to Atypical Antipsychotics for Cognitive Dysfunction in Schizophrenia
NCT01133847	PHASE4	COMPLETED	Interventions for Children With Attention and Reading Disorders
NCT01156051	PHASE4	TERMINATED	Effect of Guanfacine Extended-Release on Attention Deficit Hyperactivity Disorder (ADHD)-Associated Insomnia
NCT01238575	PHASE4	COMPLETED	Guanfacine for the Treatment of Hyperactivity in Pervasive Developmental Disorder
NCT01681264	PHASE4	TERMINATED	Effect of Guanfacine on Opioid-induced Hyperalgesia (OIH) and Tolerance
NCT01709695	PHASE4	COMPLETED	Neurobiological Basis of Response to Guanfacine Extended Release in Children and Adolescents With ADHD
NCT02048241	PHASE4	COMPLETED	Intuniv vs Placebo in the Treatment of Childhood Intermittent Explosive Disorder
NCT02141113	PHASE4	COMPLETED	Efficacy and Safety Eval of Guanfacine Hydrochloride in Combination With Psychostimulants in Adults (18-65).
NCT02699125	PHASE4	COMPLETED	Treatment of OSA Associated Hypertension With Alpha 2 Agonist or Diuretic
NCT04085172	PHASE4	COMPLETED	A Study of TAK-503 in Children and Teenagers With Attention Deficit Hyperactivity Disorder (ADHD)
NCT04181736	PHASE4	COMPLETED	The BIomarker Guided (BIG) Study for Depression
NCT03116126	PHASE3	ACTIVE_NOT_RECRUITING	Noradrenergic Add-on Therapy With Guanfacine
NCT00004376	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine for Tourette Syndrome and Attention Deficit Hyperactivity Disorder
NCT00389675	PHASE3	TERMINATED	DORADO-AC-EX - A Long-Term Safety Extension Study to the Phase 3 DORADOC-AC Study (Protocol DAR-312) of Darusentan in Resistant Hypertension
NCT00389779	PHASE3	COMPLETED	DORADO-AC - Optimized Doses of Darusentan as Compared to an Active Control in Resistant Hypertension
NCT04578886	PHASE3	COMPLETED	The Effect of Guanfacine on Delirium in Critically Ill Patients
NCT06408246	PHASE2	RECRUITING	ACE-D Aim 3 Clinical Cognitive Trial to Enhance Translation in Depression
NCT00613015	PHASE2	COMPLETED	Stress and Medication Effects on Cocaine Cue Reactivity
NCT00773357	PHASE2	COMPLETED	Modeling Stress-precipitated Smoking Behavior for Medication Development
NCT00955253	PHASE2	COMPLETED	Guanfacine for the Treatment of Spatial Neglect and Impaired Vigilance
NCT01904526	PHASE2	COMPLETED	PK/PD Comparison of Guanfacine ER and IR
NCT02051309	PHASE2	COMPLETED	Guanfacine Clinical Trial for Smoking Cessation
NCT02164422	PHASE2	COMPLETED	Does Guanfacine Attenuate Stress-Induced Drinking?
NCT02524899	PHASE2	COMPLETED	CRT-Guanfacine for SPD
NCT03865940	PHASE2	COMPLETED	Efficacy of Guanfacine and Lidocaine Combination in Trigeminal Nerve Block for Pain Management in Trigeminal Neuropathy
NCT03980184	PHASE2	COMPLETED	Guanfacine to Improve Substance Use Outcomes in Women
NCT04742673	PHASE2	COMPLETED	Maximizing trEatment of Neurological Dysfunction Using INtravenous Guanfacine Study
NCT06042257	PHASE2	TERMINATED	Guanfacine for Hyperactivity in Children With Down Syndrome (HYPEbeGONE_DS)
NCT06642181	PHASE1	RECRUITING	Combined Guanfacine and Mindfulness Meditation as an Adjunct to Buprenorphine Maintenance in Opioid Use Disorder
NCT00018603	PHASE1	COMPLETED	Guanfacine for the Treatment of Post Traumatic Stress Disorder (PTSD)
NCT00223717	PHASE1	COMPLETED	Treatment of Supine Hypertension in Autonomic Failure
NCT00585754	PHASE1	COMPLETED	Guanfacine to Reduce Stress-Induced Cocaine/Alcohol Craving and Relapse
NCT01467999	PHASE1	COMPLETED	Open-Label Pilot Study of Guanfacine-Extended Release for the Treatment of Cannabis Dependence
NCT00025779	Not specified	COMPLETED	Methylphenidate in Children and Adolescents With Pervasive Developmental Disorders
NCT00358969	Not specified	UNKNOWN	Guanfacine to Treat Borderline Personality Disorder
NCT00935493	Not specified	COMPLETED	Guanfacine Treatment for Prefrontal Cognitive Dysfunction in Elderly Subjects
NCT01600885	Not specified	COMPLETED	The Effects of Ketamine and Guanfacine on Working Memory in Healthy Subjects

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.

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

Molecule	Source	Status	Shared targets
ACLIDINIUM BROMIDE	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
Afatinib	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
Almotriptan	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CHENODIOL	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CLOZAPINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
DESLORATADINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
NAPHAZOLINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
OLANZAPINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
OLODATEROL	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
PALIPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
PRAMIPEXOLE	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
TAMSULOSIN	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
TEGASEROD	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
ALFUZOSIN	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
AMISULPRIDE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
AMOXAPINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
APOMORPHINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
APRACLONIDINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
ASENAPINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
AZELASTINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BENFLUOREX	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BENPERIDOL	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BENZBROMARONE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BENZQUINAMIDE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BENZTHIAZIDE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BENZTROPINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BITHIONOL	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BRIMONIDINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BROMPERIDOL	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CABERGOLINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CARIPRAZINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CARVEDILOL	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CHLOROQUINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CINNARIZINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CISAPRIDE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CLEMASTINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CLONIDINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
DANAZOL	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
DARIFENACIN	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
DEXMEDETOMIDINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
DOBUTAMINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
DOMPERIDONE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
DOTHIEPIN	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C