Molindone

Summary

Molindone (CHEMBL460) is an approved small molecule (ATC N05AE02) targeting HRH1 and HTR2A; indicated across 2 conditions including psychotic disorder and attention deficit-hyperactivity disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N05AE02
• Targets: 2 (HRH1, HTR2A)
• Indications: 2 conditions
• Clinical trials: 9
• Chemistry: 276.37 Da · C16H24N2O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL460
Name	Molindone
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	23897
ATC	N05AE02
Molecular formula	C16H24N2O2
Molecular weight	276.37
InChIKey	KLPWJLBORRMFGK-UHFFFAOYSA-N

SMILES: CCC1=C(NC2=C1C(=O)C(CC2)CN3CCOCC3)C

IUPAC name: 3-ethyl-2-methyl-5-(morpholin-4-ylmethyl)-1,5,6,7-tetrahydroindol-4-one

Also known as: Molindona, Molindone, Spn-810, SID90341242, SID26755691, SID50111112, molindone, MOLINDONE

Parent form; salt/anhydrous children: CHEMBL1200419

Patent coverage: 2,022 distinct patent families (7,611 SureChEMBL compound mentions), from 1 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
HRH1	H1 receptor	Antagonist	5.7	0%	P35367
HTR2A	5-HT2A receptor	Antagonist	6.5	0%	P28223

Broader ChEMBL bioactivity targets: 14 (assay-derived). Sample: 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Alpha-2C adrenergic receptor, Alpha-2B adrenergic receptor, D(1A) dopamine receptor, D(2) dopamine receptor, 5-hydroxytryptamine receptor 2A, Alpha-1A adrenergic receptor, D(3) dopamine receptor, Delta-type opioid receptor.

Bioactivity

ChEMBL activities: 16 potent at pChembl ≥ 5 of 21 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P61169	7.48	Ki	33.11	nM	CHEMBL_ACT_1300746
P61169	7.48	Ki	33.11	nM	CHEMBL_ACT_50508
ADRA2B	7.03	AC50	93.1	nM	CHEMBL_ACT_25143552
HTR2B	6.92	AC50	120	nM	CHEMBL_ACT_25164063
DRD2	6.68	AC50	209.4	nM	CHEMBL_ACT_25140178
HTR7	6.58	Ki	265	nM	CHEMBL_ACT_73720
DRD3	6.52	AC50	300.5	nM	CHEMBL_ACT_25193377
HTR2B	6.13	AC50	735.7	nM	CHEMBL_ACT_25227384
DRD1	6.11	AC50	770	nM	CHEMBL_ACT_25180372
P14842	5.85	Ki	1413	nM	CHEMBL_ACT_1300747
P14842	5.85	Ki	1413	nM	CHEMBL_ACT_50509
P18901	5.8	Ki	1585	nM	CHEMBL_ACT_50507
ADRA2A	5.7	AC50	2020	nM	CHEMBL_ACT_25219751
ADRA2C	5.68	AC50	2066	nM	CHEMBL_ACT_25147722
ADRA2A	5.02	AC50	9600	nM	CHEMBL_ACT_25155892
HTR2A	5.02	AC50	9578	nM	CHEMBL_ACT_25173559

Target pathways

Aggregated over 2 target gene(s): HRH1, HTR2A.

Top Reactome pathways

9 total, by targets touching each:

Pathway	Targets	Genes
G alpha (q) signalling events	2	HRH1, HTR2A
Signal Transduction	1	HTR2A
Signaling by GPCR	1	HTR2A
Class A/1 (Rhodopsin-like receptors)	1	HTR2A
Amine ligand-binding receptors	1	HTR2A
GPCR downstream signalling	1	HTR2A
Histamine receptors	1	HRH1
Serotonin receptors	1	HTR2A
GPCR ligand binding	1	HTR2A

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	2
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	2
chemical synaptic transmission	2
memory	2
positive regulation of vasoconstriction	2
signal transduction	2
phospholipase C-activating serotonin receptor signaling pathway	2
inflammatory response	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
visual learning	1
regulation of vascular permeability	1
regulation of synaptic plasticity	1
cellular response to histamine	1
temperature homeostasis	1
positive regulation of cytokine production involved in immune response	1

Indications & clinical

Indications

2 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
psychotic disorder	4	MONDO:0005485	EFO:0005407
attention deficit-hyperactivity disorder	3	MONDO:0007743	EFO:0003888

Clinical trials

Total trials: 9.

Phase distribution

Phase	Trials
PHASE3	4
PHASE2	4
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT02618408	PHASE3	COMPLETED	Treatment of Impulsive Aggression in Subjects With ADHD in Conjunction With Standard ADHD Treatment (CHIME 1)
NCT02618434	PHASE3	COMPLETED	Treatment of Impulsive Aggression in Subjects With ADHD in Conjunction With Standard ADHD Treatment (CHIME 2)
NCT02691182	PHASE3	TERMINATED	Treatment of Impulsive Aggression in Subjects With ADHD in Conjunction With Standard ADHD Treatment (CHIME 4)
NCT03597503	PHASE3	TERMINATED	Treatment of Impulsive Aggression (IA) in Adolescent With ADHD in Conjunction With Standard ADHD Treatment
NCT00626236	PHASE2	COMPLETED	Phase 2a Study of Safety and Tolerability of SPN-810 in Children With ADHD and Persistent Serious Conduct Problems
NCT01364662	PHASE2	COMPLETED	A Study to Evaluate the Efficacy and Safety of SPN-810 as Adjunctive Therapy in Children With Impulsive Aggression Comorbid With Attention-Deficit/Hyperactivity Disorder (ADHD)
NCT01416064	PHASE2	COMPLETED	Open-Label, Extension Study to 810P202
NCT03638466	PHASE2	TERMINATED	Exploratory fMRI Study on the Treatment for Impulsive Aggression in Children With ADHD

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.

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

Molecule	Source	Status	Shared targets
Almotriptan	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HTR2A
Crizotinib	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HTR2A
DESLORATADINE	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HTR2A
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HTR2A
Erythromycin	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HTR2A
Fidaxomicin	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HTR2A
Olodaterol	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HTR2A
PALIPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HTR2A
PRAMIPEXOLE	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HTR2A
Propoxyphene	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HTR2A
Tamsulosin	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HTR2A
ABEMACICLIB	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
AMIODARONE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
AMISULPRIDE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
AMOXAPINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
APOMORPHINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
ASENAPINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
ATOMOXETINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
AZATADINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
AZELASTINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
BENFLUOREX	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
BENPERIDOL	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
BENZBROMARONE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
BENZTROPINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
BEPRIDIL	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
BROMPERIDOL	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
BUSPIRONE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
BUTRIPTYLINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
CABERGOLINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
CAPTOPRIL	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
CARIPRAZINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
CETIRIZINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
CHLORPHENIRAMINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
CHLORPHENTERMINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
CINACALCET	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
CINNARIZINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
CISAPRIDE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
CITALOPRAM	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
CLEMASTINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
CLOZAPINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
CYCLIZINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
CYCLOBENZAPRINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
DESIPRAMINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
DEXBROMPHENIRAMINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
DEXCHLORPHENIRAMINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
DIBENZEPIN	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
DICYCLOMINE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
DIETHYLPROPION	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
DIMENHYDRINATE	ChEMBL	Phase 4 (approved)	HRH1, HTR2A
DIPHEMANIL	ChEMBL	Phase 4 (approved)	HRH1, HTR2A