DRD3

Summary

DRD3 (dopamine receptor D3, HGNC:3024) is a protein-coding gene on chromosome 3q13.31, encoding D(3) dopamine receptor (P35462). Dopamine receptor that is primarily expressed in limbic areas of the brain and is involved in the modulation of cognitive, emotional, and endocrine functions.

This gene encodes the D3 subtype of the five (D1-D5) dopamine receptors. The activity of the D3 subtype receptor is mediated by G proteins which inhibit adenylyl cyclase. This receptor is localized to the limbic areas of the brain, which are associated with cognitive, emotional, and endocrine functions. Genetic variation in this gene may be associated with susceptibility to hereditary essential tremor 1. Alternative splicing of this gene results in transcript variants encoding different isoforms, although some variants may be subject to nonsense-mediated decay (NMD).

Source: NCBI Gene 1814 — RefSeq curated summary.

At a glance

• Gene–disease (curated): schizophrenia (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 72 total
• Phenotypes (HPO): 12
• Druggable target: yes — 448 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000796

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3024
Approved symbol	DRD3
Name	dopamine receptor D3
Location	3q13.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000151577
Ensembl biotype	protein_coding
OMIM	126451
Entrez	1814

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 nonsense_mediated_decay

ENST00000295881, ENST00000383673, ENST00000460779, ENST00000467632, ENST00000698213

RefSeq mRNA: 4 — MANE Select: NM_000796 NM_000796, NM_001282563, NM_001290809, NM_033663

CCDS: CCDS2978, CCDS33829

Canonical transcript exons

ENST00000383673 — 7 exons

Exon	Start	End
ENSE00001000454	114159755	114159867
ENSE00001157158	114147415	114147557
ENSE00001194749	114139500	114139696
ENSE00001225059	114171723	114172027
ENSE00001384028	114178657	114179052
ENSE00003972975	114127580	114128912
ENSE00003972976	114131118	114131400

Expression profiles

Bgee: expression breadth broad, 25 present calls, max score 92.21.

Top tissues by expression

245 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.21	gold quality
metanephric glomerulus	UBERON:0004736	72.03	gold quality
endometrium epithelium	UBERON:0004811	71.54	gold quality
nucleus accumbens	UBERON:0001882	68.32	gold quality
putamen	UBERON:0001874	57.71	gold quality
caudate nucleus	UBERON:0001873	56.22	gold quality
granulocyte	CL:0000094	55.00	gold quality
thymus	UBERON:0002370	51.82	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.85	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
lower lobe of lung	UBERON:0008949	49.59	silver quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
layer of synovial tissue	UBERON:0007616	46.56	gold quality
quadriceps femoris	UBERON:0001377	46.10	gold quality
vastus lateralis	UBERON:0001379	45.23	gold quality
trachea	UBERON:0003126	44.40	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
oviduct epithelium	UBERON:0004804	42.62	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
dorsal root ganglion	UBERON:0000044	41.10	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
dorsal plus ventral thalamus	UBERON:0001897	40.64	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.10

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1D1, RORA

Literature-anchored findings (GeneRIF, showing 40)

• Significant association of schizophrenia with DRD3 haplotype pairs, which includes 4 SNPs in a 768 bp region with the S9G polymorphism. (PMID:10670776)
• The Ser9Gly polymorphism in the DRD3 gene are not associated with EH. However, our negative result does not exclude the possibility of another variant elsewhere in or near the DRD3 gene in EH (PMID:11796958)
• it is unlikely that DRD3 is playing a major role in the etiology of attention-deficit hyperactivity disorder (PMID:11864723)
• ABP-280 interacts with dopamine D(3) receptors. (PMID:11911837)
• characterisation, mutation detection, and association analysis of alternative promoters and 5’ UTRs of the human gene in schizophrenia (PMID:12082567)
• Gly/Gly homozygotes in MscI polymorphic site of dopamine d3 receptor gene may be involved in pathogenesis of tardive dyskinesia in schizophrenics (PMID:12109967)
• protein 4.1N/dopamine receptor interaction is required for localization or stability of dopamine receptors at the neuronal plasma membrane. (PMID:12181426)
• An epistatic interaction of the PDYN gene polymorphism with the GLY allele of the DRD3 gene may contribute to susceptibility for schizophrenia. (PMID:12207142)
• This study suggests that these polymorphisms are not related to the development of tardive dystonia. (PMID:12210290)
• no association between this gene and Korean alcohol dependence (PMID:12218663)
• Significant age-related decline was observed for dopamine receptor mRNAs in the hippocampus and entorhinal cortex (PMID:12509874)
• DRD3 polymorphisms investigated have no major impact on personality in the investigated population (PMID:12555237)
• Meta-analysis suggests that the DRD3 gene Ser9Gly variation confers susceptibility to schizophrenia. (PMID:12605094)
• An association analysis for dopamine D3 receptor polymorphism and p300 component in normal young women is negative. (PMID:12605102)
• Variations of the DRD3 gene are likely involved in the regulation of impulsivity and some psychopathological aspects of ADHD related to violent behavior. (PMID:12721816)
• extrastriatal D(2/3) density in drug-naive schizophrenic patients (PMID:12740603)
• Among type 1 alcoholics dopamine transporters are lower in nucleus accumbens and dopamine D(2), but not D(1) or D(3) receptors in nucleus accumbens and amygdala. Lower dopamine receptor density is specific for D(2) receptor and for type 1 alcoholism. (PMID:12781734)
• Chinese Han patients with schizophrenia assessed for abnormal involuntary movements and DRD3 polymorphism. (PMID:12960753)
• A shared variance of at least 17% (p=0.016) between DRD3 mRNA expression in peripheral blood lymphocytes and the personality trait of persistence is found. (PMID:15081259)
• dopaminergic neurons could regulate ERK activity more flexibly through alternative usage of either the D(2)R or D(3)R pathway depending on the cellular situation (PMID:15102843)
• The D3 receptor exhibits a tolerance property wherein the magnitude of the second agonist-induced response is reduced by 60%. The D3 receptor response terminates 15-fold more slowly upon agonist removal. (PMID:15121186)
• no associations between the dopamine receptor D3 BalI polymorphism and psychotic symptoms in Alzheimer’s disease (PMID:15342129)
• Phospholipase D activation is a novel finding for the D(3) receptor, and is the first example of an effector system where D(3) signals without G(i)/G(o) protein intermediates. (PMID:15500962)
• A single nucleotide polymorphism in the dopamine D3 receptor causes a shift from cAMP to a PGE2 signal transduction pathway. (PMID:15520413)
• the expression of DRD3 mRNA is reduced in schizophrenia and bipolar disorder. (PMID:15539862)
• The BDNF val66met genetic polymorphism may exert its effect on the clinically phenotypic variability after Tardive Dyskinesia has occurred. Further replication studies with larger sample size and stringent definition for TD is necessary. (PMID:15626824)
• DRD3 polymorphism may influence response to risperidone in negative symptoms and social functioning (PMID:15643094)
• D3R, filamin A, and beta-arrestin form a signaling complex that is destabilized by agonist- or expression-mediated increases in GRK2/3 activity (PMID:15687500)
• These results suggest that the DRD3 variant containing glycine is associated with more efficient striatal habit learning in healthy controls and patients with schizophrenia. (PMID:15998189)
• Interaction of the functional Val66Met polymorphism of the BDNF gene with DR# ser9gly polymorphism influencing age at onset in schizophrenia. (PMID:16056149)
• This study found diminished parietal and increased frontal P300 amplitudes in Gly9 homozygotes in comparison to Ser9 carriers. This finding suggests a possible role of the DRD3 receptor gene in the interindividual variation of P300 amplitudes. (PMID:16395310)
• DRD3 may contribute to the development of -compulsive personality disorder. (PMID:16583407)
• A glycine-9 variant DRD3 receptor may confer susceptibility to essential tremor. (PMID:16809426)
• Dopamine, D2/D3- and D4-specific agonists inhibited histamine- but not thrombin-induced VWF secretion; the dopamine effects are not mediated by Ca(2+)-dependent signalling or cAMP-mediated signaling (PMID:16839358)
• results did not support the hypothesis that Ser9Gly polymorphism of the DRD3 gene influences the response to typical antipsychotics in our sample of schizophrenics (PMID:17119697)
• No association was found between schizophrenia and the Ser9Gly polymorphism of the D3 dopamine receptor gene. (PMID:17171662)
• Presence of “non-negligible” specific [(123)I]epidepride binding to dopamine D(2)/D(3) receptors in the cerebellum. (PMID:17175177)
• Genetic variations within the DRD3 gene may not contribute significantly to interindividual differences in the therapeutic efficacy of risperidone in schizophrenia. (PMID:17429404)
• These results suggest a role for the dopamine D(3) receptor in the mediation of human prepulse inhibition (PMID:17579840)
• Monoclonal antibodies against all three D(2)-like receptors were used to localize receptors in Ntera-2 (NT-2) cells, the human neuronal precursor cell line and rat cerebral cortex and hippocampus. (PMID:17593530)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	drd3	ENSDARG00000032131
mus_musculus	Drd3	ENSMUSG00000022705
rattus_norvegicus	Drd3	ENSRNOG00000060806

Paralogs (25): DRD4 (ENSG00000069696), HRH3 (ENSG00000101180), HRH2 (ENSG00000113749), CHRM3 (ENSG00000133019), HRH4 (ENSG00000134489), TAAR5 (ENSG00000135569), GPR84 (ENSG00000139572), GPR161 (ENSG00000143147), TAAR2 (ENSG00000146378), TAAR6 (ENSG00000146383), TAAR8 (ENSG00000146385), TAAR1 (ENSG00000146399), HTR4 (ENSG00000164270), CHRM1 (ENSG00000168539), DRD5 (ENSG00000169676), HTR1A (ENSG00000178394), HTR1D (ENSG00000179546), CHRM4 (ENSG00000180720), CHRM2 (ENSG00000181072), DRD1 (ENSG00000184845), CHRM5 (ENSG00000184984), GPR21 (ENSG00000188394), HRH1 (ENSG00000196639), GPR52 (ENSG00000203737), TAAR9 (ENSG00000237110)

Protein

Protein identifiers

D(3) dopamine receptor — P35462 (reviewed: P35462)

Alternative names: Dopamine D3 receptor

All UniProt accessions (4): P35462, A0A8V8TLH3, E9PCM4, X5D2G4

UniProt curated annotations — full annotation on UniProt →

Function. Dopamine receptor that is primarily expressed in limbic areas of the brain and is involved in the modulation of cognitive, emotional, and endocrine functions. Plays a key role in regulating neuronal signaling pathways associated with motivation, reward, and behavior. Coupled to G(i)/G(o) proteins; activation leads to inhibition of adenylate cyclase and decreased intracellular cAMP levels. Involved in the control of locomotor activity and implicated in several neuropsychiatric disorders, including schizophrenia and substance use disorders. Promotes cell proliferation through MAP kinase signaling. Also involved in autophagy regulation: receptor activation stimulates AMPK, which phosphorylates RPTOR and enhances its interaction with MTOR, thereby inhibiting MTORC1 signaling and its downstream target RPS6KB1. This leads to activation of ULK1 and initiation of the autophagy cascade. Forms heterotetramers with DRD1 to potentiate beta-arrestin recruitment and mediate locomotor activity.

Subunit / interactions. Interacts with CLIC6. Interacts with GRK4. Interacts with PALM. Interacts with FLNA (via filamin repeat 21); increases PKA-mediated phosphorylation of FLNA. Interacts with DRD1.

Subcellular location. Cell membrane.

Tissue specificity. Brain.

Post-translational modifications. Phosphorylated by GRK4 (GRK4-alpha and GRK4-gamma). Palmitoylated.

Disease relevance. Tremor, hereditary essential 1 (ETM1) [MIM:190300] A common movement disorder mainly characterized by postural tremor of the arms. Head, legs, trunk, voice, jaw, and facial muscles may also be involved. The condition can be aggravated by emotions, hunger, fatigue and temperature extremes, and may cause a functional disability or even incapacitation. Inheritance is autosomal dominant. Disease susceptibility is associated with variants affecting the gene represented in this entry. Glycine at position 9 results in gain of function and is associated with susceptibility to essential tremor. Schizophrenia (SCZD) [MIM:181500] A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Glycine at position 9 results in gain of function and may be a risk factor for schizophrenia.

Similarity. Belongs to the G-protein coupled receptor 1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P35462-1	1, D3	yes
P35462-3	3

RefSeq proteins (4): NP_000787, NP_001269492, NP_001277738, NP_387512 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000929	Dopamine_rcpt	Family
IPR001620	Dopamine_D3_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (42 total): helix 13, topological domain 8, transmembrane region 7, glycosylation site 4, binding site 3, disulfide bond 2, chain 1, splice variant 1, sequence variant 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
7CMV	ELECTRON MICROSCOPY	2.7
8IRT	ELECTRON MICROSCOPY	2.7
3PBL	X-RAY DIFFRACTION	2.89
7CMU	ELECTRON MICROSCOPY	3
9F33	ELECTRON MICROSCOPY	3.05
9F34	ELECTRON MICROSCOPY	3.09
9R42	ELECTRON MICROSCOPY	3.24

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35462-F1	75.70	0.47

Antibody-complex structures (SAbDab): 3 — 7CMU, 7CMV, 8IRT

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 110; 345; 349

Disulfide bonds (2): 103–181, 355–358

Glycosylation sites (4): 12, 19, 97, 173

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-390651	Dopamine receptors
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 295 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_POTASSIUM_ION_TRANSPORT, GOBP_G_PROTEIN_COUPLED_RECEPTOR_INTERNALIZATION, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_MITOTIC_NUCLEAR_DIVISION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_ACID_SECRETION, GOBP_COGNITION, MODULE_274, GOBP_BEHAVIOR, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_NEGATIVE_REGULATION_OF_OLIGODENDROCYTE_DIFFERENTIATION, GOBP_CIRCULATORY_SYSTEM_PROCESS

GO Biological Process (40): G protein-coupled receptor internalization (GO:0002031), intracellular calcium ion homeostasis (GO:0006874), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating dopamine receptor signaling pathway (GO:0007191), adenylate cyclase-inhibiting dopamine receptor signaling pathway (GO:0007195), learning or memory (GO:0007611), learning (GO:0007612), locomotory behavior (GO:0007626), visual learning (GO:0008542), response to xenobiotic stimulus (GO:0009410), regulation of dopamine secretion (GO:0014059), positive regulation of cytokinesis (GO:0032467), circadian regulation of gene expression (GO:0032922), response to histamine (GO:0034776), social behavior (GO:0035176), response to cocaine (GO:0042220), dopamine metabolic process (GO:0042417), regulation of potassium ion transport (GO:0043266), response to morphine (GO:0043278), negative regulation of blood pressure (GO:0045776), positive regulation of mitotic nuclear division (GO:0045840), acid secretion (GO:0046717), behavioral response to cocaine (GO:0048148), negative regulation of oligodendrocyte differentiation (GO:0048715), arachidonate secretion (GO:0050482), negative regulation of protein secretion (GO:0050709), musculoskeletal movement, spinal reflex action (GO:0050883), negative regulation of cytosolic calcium ion concentration (GO:0051481), regulation of dopamine uptake involved in synaptic transmission (GO:0051584), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), negative regulation of synaptic transmission, glutamatergic (GO:0051967), prepulse inhibition (GO:0060134), phospholipase C-activating dopamine receptor signaling pathway (GO:0060158), positive regulation of dopamine receptor signaling pathway (GO:0060161), synaptic transmission, dopaminergic (GO:0001963), signal transduction (GO:0007165), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), negative regulation of G protein-coupled receptor signaling pathway (GO:0045744), regulation of amine transport (GO:0051952), regulation of secretion by cell (GO:1903530)

GO Molecular Function (4): dopamine neurotransmitter receptor activity, coupled via Gi/Go (GO:0001591), G protein-coupled receptor activity (GO:0004930), dopamine neurotransmitter receptor activity (GO:0004952), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), synapse (GO:0045202), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Amine ligand-binding receptors	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled dopamine receptor signaling pathway	3
behavior	3
desensitization of G protein-coupled receptor signaling pathway	1
receptor internalization	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
cognition	1
learning or memory	1
visual behavior	1
associative learning	1
response to chemical	1
dopamine secretion	1
regulation of catecholamine secretion	1
cytokinesis	1
regulation of cytokinesis	1
positive regulation of cell division	1
positive regulation of cell cycle process	1
circadian rhythm	1
regulation of gene expression	1
response to nitrogen compound	1
biological process involved in intraspecies interaction between organisms	1
response to alkaloid	1
response to oxygen-containing compound	1
catecholamine metabolic process	1
potassium ion transport	1
regulation of metal ion transport	1
response to isoquinoline alkaloid	1
regulation of blood pressure	1
dopamine neurotransmitter receptor activity	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
synaptic transmission, dopaminergic	1
dopamine binding	1
postsynaptic neurotransmitter receptor activity	1
binding	1
membrane	1

Protein interactions and networks

STRING

1490 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DRD3	BDNF	P23560	839
DRD3	SLC6A4	P31645	785
DRD3	COMT	P21964	784
DRD3	SLC6A3	Q01959	779
DRD3	DRD1	P21728	697
DRD3	MAOB	P27338	692
DRD3	ANKK1	Q8NFD2	668
DRD3	GRIN2B	Q13224	649
DRD3	MAOA	P21397	641
DRD3	GABRB2	P47870	607
DRD3	DTNBP1	Q96EV8	593
DRD3	TOMT	Q8WZ04	586
DRD3	DISC1	Q9NRI5	583
DRD3	TPH1	P17752	582
DRD3	DAOA	P59103	572

IntAct

9 interactions, top by confidence:

A	B	Type	Score
RAMP1	DRD3	psi-mi:“MI:0915”(physical association)	0.400
DRD3	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
DRD3	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
DRD3	GPR143	psi-mi:“MI:2364”(proximity)	0.380
ADORA2A	DRD3	psi-mi:“MI:2364”(proximity)	0.380
DRD3	GPR143	psi-mi:“MI:0403”(colocalization)	0.380
DRD3	ADORA2A	psi-mi:“MI:0403”(colocalization)	0.380
DRD3	DUSP14	psi-mi:“MI:0914”(association)	0.350

BioGRID (40): PRKCB (Affinity Capture-Western), CLIC6 (Two-hybrid), MPDZ (Two-hybrid), GIPC1 (Two-hybrid), RDX (Two-hybrid), CLIC6 (Reconstituted Complex), DRD3 (Affinity Capture-Western), DRD1 (Affinity Capture-Western), DRD3 (FRET), PDCD6IP (Two-hybrid), PDCD6IP (Reconstituted Complex), PDCD6IP (Affinity Capture-Western), DRD3 (Affinity Capture-Western), DRD3 (Affinity Capture-Western), EPB41L1 (Reconstituted Complex)

ESM2 similar proteins: O02824, O46635, O73810, O77680, P04274, P07550, P10608, P15823, P18130, P18762, P18841, P18901, P19020, P21728, P25115, P30728, P35348, P35368, P35462, P42288, P42290, P42291, P43140, P50130, P52703, P53452, P53453, P53454, P54833, P70174, P97292, P97717, P97718, Q28044, Q28509, Q28997, Q4KWL2, Q5IS72, Q5R4Q6, Q61616

Diamond homologs: A1ZAX0, B2ZI34, E7F7V7, F1MV99, F1R332, O08726, O08786, O43603, O54798, O54799, O62709, O88626, O88854, O97666, O97772, O97967, P05363, P08911, P08912, P21451, P21729, P22270, P24053, P24530, P25101, P26684, P28088, P28336, P28646, P30550, P30551, P30552, P30553, P30796, P30872, P30873, P30937, P30974, P31391, P32238

SIGNOR signaling

34 interactions.

A	Effect	B	Mechanism
DRD3	“up-regulates activity”	GNAI1	binding
DRD3	“up-regulates activity”	GNAI3	binding
DRD3	“up-regulates activity”	GNAO1	binding
DRD3	“up-regulates activity”	GNAZ	binding
dopamine	“up-regulates activity”	DRD3	“chemical activation”
DRD3	“up-regulates activity”	GNB5	binding
amisulpride	“down-regulates activity”	DRD3	“chemical inhibition”
bromocriptine	“up-regulates activity”	DRD3	“chemical activation”
clozapine	“down-regulates activity”	DRD3	“chemical inhibition”
chlorpromazine	“down-regulates activity”	DRD3	“chemical inhibition”
haloperidol	“down-regulates activity”	DRD3	“chemical inhibition”
apomorphine	“up-regulates activity”	DRD3	“chemical activation”
pimozide	“down-regulates activity”	DRD3	“chemical inhibition”
domperidone	“down-regulates activity”	DRD3	“chemical inhibition”
sulpiride	“down-regulates activity”	DRD3	“chemical inhibition”
Isoetharine	“up-regulates activity”	DRD3	“chemical activation”
“1-phospho-alpha-D-glucuronic acid”	“up-regulates activity”	DRD3	“chemical activation”
“2-N,6-N-Bis(2,3-dihydroxy-N-benzoyl)-L-serine amide”	“up-regulates activity”	DRD3	“chemical activation”
“3-phenanthryl hydrogen sulfate”	“down-regulates activity”	DRD3	“chemical inhibition”
quinpirole	“up-regulates activity”	DRD3	“chemical activation”
sertindole	“down-regulates activity”	DRD3	“chemical inhibition”
zotepine	“down-regulates activity”	DRD3	“chemical inhibition”
ropinirole	“up-regulates activity”	DRD3	“chemical activation”
cis-(z)-Flupenthixol	“down-regulates activity”	DRD3	“chemical inhibition”
7-(dipropylamino)-5,6,7,8-tetrahydronaphthalen-2-ol	“up-regulates activity”	DRD3	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

72 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	14
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

1612 predictions. Top by Δscore:

Variant	Effect	Δscore
3:114139494:ACTT:A	donor_loss	1.0000
3:114139496:TTA:T	donor_loss	1.0000
3:114139497:TA:T	donor_loss	1.0000
3:114139498:A:AC	donor_gain	1.0000
3:114139498:A:T	donor_loss	1.0000
3:114139499:C:CT	donor_gain	1.0000
3:114139499:CTTG:C	donor_gain	1.0000
3:114139693:TCCC:T	acceptor_gain	1.0000
3:114139694:CCC:C	acceptor_gain	1.0000
3:114139694:CCCC:C	acceptor_gain	1.0000
3:114139694:CCCCT:C	acceptor_loss	1.0000
3:114139695:CC:C	acceptor_gain	1.0000
3:114139695:CCC:C	acceptor_gain	1.0000
3:114139695:CCCTG:C	acceptor_loss	1.0000
3:114139696:CC:C	acceptor_gain	1.0000
3:114139696:CCTGT:C	acceptor_loss	1.0000
3:114139697:C:CA	acceptor_loss	1.0000
3:114139697:C:CC	acceptor_gain	1.0000
3:114139698:T:A	acceptor_loss	1.0000
3:114165688:T:TA	donor_gain	1.0000
3:114171718:CTCA:C	donor_loss	1.0000
3:114171719:TCACC:T	donor_loss	1.0000
3:114171720:CA:C	donor_loss	1.0000
3:114171721:ACCT:A	donor_gain	1.0000
3:114171722:C:A	donor_loss	1.0000
3:114171722:CCTC:C	donor_gain	1.0000
3:114172024:CTTC:C	acceptor_gain	1.0000
3:114172025:TTCC:T	acceptor_loss	1.0000
3:114172026:TCC:T	acceptor_loss	1.0000
3:114172028:C:CC	acceptor_gain	1.0000

AlphaMissense

2581 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:114159763:G:C	S125R	1.000
3:114159763:G:T	S125R	1.000
3:114159765:T:G	S125R	1.000
3:114159787:G:C	S117R	1.000
3:114159787:G:T	S117R	1.000
3:114159789:T:G	S117R	1.000
3:114171769:T:G	D75A	1.000
3:114171783:G:C	S70R	1.000
3:114171783:G:T	S70R	1.000
3:114171785:T:G	S70R	1.000
3:114128749:G:C	F390L	0.999
3:114128749:G:T	F390L	0.999
3:114128750:A:C	F390C	0.999
3:114128750:A:G	F390S	0.999
3:114128751:A:G	F390L	0.999
3:114128782:G:C	N379K	0.999
3:114128782:G:T	N379K	0.999
3:114128794:A:C	N375K	0.999
3:114128794:A:T	N375K	0.999
3:114128881:G:C	F346L	0.999
3:114128881:G:T	F346L	0.999
3:114128883:A:G	F346L	0.999
3:114128884:G:C	F345L	0.999
3:114128884:G:T	F345L	0.999
3:114128886:A:G	F345L	0.999
3:114128895:A:G	W342R	0.999
3:114128895:A:T	W342R	0.999
3:114128905:G:C	F338L	0.999
3:114128905:G:T	F338L	0.999
3:114128907:A:G	F338L	0.999

dbSNP variants (sampled 300 via entrez): RS1000018054 (3:114147010 A>G), RS1000032179 (3:114191441 T>C), RS1000045770 (3:114136007 A>G), RS1000146064 (3:114142340 G>A,T), RS1000198926 (3:114184958 T>C), RS1000199586 (3:114142067 A>G), RS1000247191 (3:114191589 G>A), RS1000326666 (3:114148753 C>G), RS1000390586 (3:114146711 A>G), RS1000395655 (3:114136240 C>G), RS1000426462 (3:114197279 T>A,C), RS1000436888 (3:114155090 T>A,C), RS1000460611 (3:114172185 C>T), RS1000520049 (3:114185723 T>G), RS1000560142 (3:114165512 G>A)

Disease associations

OMIM: gene MIM:126451 | disease phenotypes: MIM:190300, MIM:181500

GenCC curated gene-disease

Disease	Classification	Inheritance
schizophrenia	Limited	Autosomal dominant
tremor, hereditary essential, 1	Limited	Autosomal dominant

Mondo (3): tremor, hereditary essential, 1 (MONDO:0008590), schizophrenia, susceptibility to (MONDO:0100182), schizophrenia (MONDO:0005090)

Orphanet (1): NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

12 total (12 of 12 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000738	Hallucinations
HP:0000746	Delusion
HP:0001260	Dysarthria
HP:0002174	Postural tremor
HP:0002345	Action tremor
HP:0002353	EEG abnormality
HP:0002378	Hand tremor
HP:0003676	Progressive
HP:0007086	Social and occupational deterioration
HP:0100753	Schizophrenia
HP:0410291	Negativism

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002111_8	Personality dimensions	6.000000e-06
GCST002361_20	Smooth-surface caries	9.000000e-06
GCST006951_42	Feeling hurt	3.000000e-08
GCST007576_270	Chronotype	2.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004365	personality trait
EFO:0009599	feeling emotionally hurt measurement
EFO:0008328	chronotype measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536545	Tremor hereditary essential, 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2095169 (SELECTIVITY GROUP), CHEMBL2096905 (PROTEIN FAMILY), CHEMBL2097165 (SELECTIVITY GROUP), CHEMBL2331075 (PROTEIN FAMILY), CHEMBL234 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

448 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 865,510 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1201087	CABERGOLINE	4	12,778
CHEMBL53	APOMORPHINE	4	25,813
CHEMBL54	HALOPERIDOL	4	60,883
CHEMBL589	ROPINIROLE	4	21,493
CHEMBL59	DOPAMINE	4	217,028
CHEMBL1000	CETIRIZINE	4	26,030
CHEMBL1006	AMIFOSTINE	4	34,963
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1042	CHOLECALCIFEROL	4	64,162
CHEMBL1064	SIMVASTATIN	4	123,163
CHEMBL1065	METHYSERGIDE	4	8,455
CHEMBL1071	OXAPROZIN	4	51,044
CHEMBL1078261	PROPIVERINE	4	4,890
CHEMBL1085	ACETOPHENAZINE	4	5,134
CHEMBL1088	MESORIDAZINE	4	12,814
CHEMBL109	VALPROIC ACID	4	65,937
CHEMBL1095777	INDACATEROL	4	2,735
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL1108	DROPERIDOL	4
CHEMBL111	RIMONABANT	4
CHEMBL1112	ARIPIPRAZOLE	4
CHEMBL1113	AMOXAPINE	4
CHEMBL1117	IDARUBICIN	4
CHEMBL1123	DICYCLOMINE	4
CHEMBL114	SAQUINAVIR	4
CHEMBL1171837	PONATINIB	4
CHEMBL1172	DESLORATADINE	4
CHEMBL1175	DULOXETINE	4

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

19 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs167770	Efficacy	3	duloxetine	Anxiety Disorders
rs167771	Toxicity	3	risperidone	Bipolar Disorder;Schizophrenia
rs2654754	Toxicity	3	opioids	Opioid-Related Disorders
rs324023	Efficacy	3	duloxetine	Anxiety Disorders
rs324026	Efficacy	3	duloxetine	Anxiety Disorders
rs324029	Toxicity	3	opioids	Opioid-Related Disorders
rs6280	Efficacy	3	clozapine	Schizophrenia
rs6280	Toxicity	3	opioids	Opioid-Related Disorders
rs6280	Toxicity	3	levodopa	Gastrointestinal toxicity;Hallucinations;Parkinson Disease
rs6280	Efficacy	3	risperidone	Autism
rs6280	Efficacy	3	pramipexole	Parkinson Disease
rs6280	Efficacy	3	olanzapine	Schizophrenia
rs6280	Efficacy	3	paroxetine	Major Depressive Disorder
rs6280	Efficacy	3	methylphenidate	Autism Spectrum Disorder
rs6280	Metabolism/PK	3	quetiapine
rs6280	Toxicity	3	methamphetamine	HIV infectious disease
rs6280	Efficacy	3	risperidone	Schizophrenia
rs9288993	Toxicity	3	opioids	Opioid-Related Disorders
rs963468	Efficacy	3	duloxetine	Anxiety Disorders

PharmGKB variants

15 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6280	DRD3	3	5.00	11	pramipexole;opioids;paroxetine;risperidone;olanzapine;clozapine;methylphenidate;quetiapine;levodopa;methamphetamine
rs167770	DRD3	3	2.00	1	duloxetine
rs167771	DRD3	3	2.75	1	risperidone
rs324023	DRD3	3	2.00	1	duloxetine
rs324026	DRD3	3	2.00	1	duloxetine
rs963468	DRD3	3	2.00	1	duloxetine
rs1486009	DRD3		0.00	0
rs2654754	DRD3	3	1.00	1	opioids
rs9288993	DRD3	3	2.00	1	opioids
rs2399496	DRD3		0.00	0
rs9817063	DRD3		0.00	0
rs3732790	DRD3		0.00	0
rs3773679	DRD3		0.00	0
rs324029	DRD3	3	2.00	1	opioids
rs11721264	DRD3		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Dopamine receptors

Most potent curated ligand interactions (63 total), top 25:

Ligand	Action	Affinity	Parameter
[3H]nemonapride	Antagonist	10.3	pKd
cariprazine	Partial agonist	10.05	pKi
[3H]spiperone	Antagonist	9.9	pKd
S33084	Antagonist	9.6	pKi
[3H]7-OH-DPAT	Agonist	9.6	pKd
lisuride	Partial agonist	9.6	pKi
perospirone	Antagonist	9.55	pKi
R-VK4-40	Antagonist	9.54	pKi
nafadotride	Antagonist	9.52	pKi
nemonapride	Antagonist	9.3	pKi
PG01037	Antagonist	9.2	pKi
spiperone	Antagonist	9.2	pKi
cabergoline	Partial agonist	9.1	pKi
[3H]PD128907	Agonist	9.0	pKd
terguride	Partial agonist	9.0	pKi
BP 897	Partial agonist	9.0	pKi
SB269652	Negative	9.0	pKi
flupentixol	Antagonist	8.96	pKi
roxindole	Partial agonist	8.9	pKi
sertindole	Antagonist	8.8	pKi
NGB 2904	Antagonist	8.8	pKi
eticlopride	Antagonist	8.8	pKi
(-)-N-porphynorapomorphine	Full agonist	8.7	pKi
pramipexole	Full agonist	8.7	pKi
haloperidol	Antagonist	8.6	pKi

Binding affinities (BindingDB)

1088 measured of 1150 human assays (1197 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[3-(2-methylsulfonylphenothiazin-10-yl)propyl]piperidine-4-carboxamide	KI	0.07 nM	US-9132134: Methods for treating GI tract disorders
NSC_104911	KI	0.1 nM
roxindole	KI	0.11 nM
N-(Trans-4-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)cyclohexyl)furan-2-carboxamide	IC50	0.12 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof
CAS_18426-20-5	KI	0.12 nM
3,3-diethyl-1-[(4R,7R)-6-methyl-6,11-diazatetracyclo[7.6.1.0^{2,7}.0^{12,16}]hexadeca-1(15),2,9,12(16),13-pentaen-4-yl]urea	KI	0.15 nM
N-(Trans-4-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)cyclohexyl)-1-hydroxycyclopropane-1-carboxamide	IC50	0.2 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof
CAS_39860-99-6	KI	0.2 nM
CAS_53772-85-3	KI	0.2 nM
CAS_14759-06-9	KI	0.2 nM
N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]-2-hydroxybutyl]-1H-indole-2-carboxamide	KI	0.26 nM	US-8748608: 4-phenylpiperazine derivatives with functionalized linkers as dopamine D3 receptor selective ligands and methods of use
(S,S)-reboxetine	KI	0.3 nM
(trans) 2-{4-[3-(4-Fluoro-phenyl)-6-trifluoromethyl-indan-1-yl]-piperazin-1-yl}-ethanol	KI	0.3 nM
(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2-(furan-3-yl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho-[2,1-c]pyran-7-carboxylic acid methyl ester	EC50	0.3 nM
CAS_51152-91-1	KI	0.3 nM
5-[3-[(5-cyclohexyl-4-methyl-1,2,4-triazol-3-yl)sulfanyl]propyl]-1-[4-(trifluoromethyl)phenyl]-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole	KI	0.331 nM	US-10273244: Substituted hexahydropyrrolo[3,4-b]pyrroles and hexahydrocyclopenta[c]pyrroles as dopamine receptor modulators
N-(Trans-4-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)cyclohexyl)-3-hydroxy-3-methylbutanamide	IC50	0.36 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof
(3aS,6aS)-5-[3-[(5-cyclohexyl-4-methyl-1,2,4-triazol-3-yl)sulfanyl]propyl]-1-[4-(trifluoromethyl)phenyl]-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole	KI	0.398 nM	US-10273244: Substituted hexahydropyrrolo[3,4-b]pyrroles and hexahydrocyclopenta[c]pyrroles as dopamine receptor modulators
5-[3-[(5-cyclohexyl-4-methyl-1,2,4-triazol-3-yl)sulfanyl]propyl]-1-(4-fluorophenyl)-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole	KI	0.407 nM	US-10273244: Substituted hexahydropyrrolo[3,4-b]pyrroles and hexahydrocyclopenta[c]pyrroles as dopamine receptor modulators
N-(Trans-4-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)cyclohexyl)oxazole-2-carboxamide	IC50	0.43 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof
NSC_92178	KI	0.45 nM
N-(Trans-4-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)cyclohexyl)-2-methoxyacetamide	IC50	0.47 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof
2-Chlor-11-(2-dimethylaminoaethoxy)-dibenzo(b,f)-thiepin	KI	0.5 nM
3,5-Dichloro-N-(1-ethyl-pyrrolidin-2-ylmethyl)-2-hydroxy-6-methoxy-benzamide(Raclopride)	KI	0.5 nM
N-[2-hydroxy-4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-1H-indole-2-carboxamide	KI	0.5 nM	US-8748608: 4-phenylpiperazine derivatives with functionalized linkers as dopamine D3 receptor selective ligands and methods of use
NSC_122245	KI	0.5 nM
1-(Cis-4-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-4-fluorocyclohexyl)-3-ethylurea	IC50	0.57 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof
N-(Trans-4-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)cyclohexyl)-5-methylfuran-2-carboxamide	IC50	0.6 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof
5-fluoro-N-[3-hydroxy-4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-1-benzofuran-2-carboxamide	KI	0.65 nM	US-8748608: 4-phenylpiperazine derivatives with functionalized linkers as dopamine D3 receptor selective ligands and methods of use
N-(Trans-4-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)cyclohexyl)-3,3-difluoro azetidine-1-carboxamide	IC50	0.76 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof
N-(4-(2-(4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-2-fluorocyclohexyl)furan-2-carboxamide	IC50	0.76 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof
N-(Cis-4-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-4-fluorocyclohexyl)furan-2-carboxamide	IC50	0.83 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof
N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]-3-hydroxybutyl]-1H-indole-2-carboxamide	KI	0.9 nM	US-8748608: 4-phenylpiperazine derivatives with functionalized linkers as dopamine D3 receptor selective ligands and methods of use
N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]-3-hydroxybutyl]-1-benzofuran-2-carboxamide	KI	0.98 nM	US-8748608: 4-phenylpiperazine derivatives with functionalized linkers as dopamine D3 receptor selective ligands and methods of use
N-[3-hydroxy-4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-5-methoxy-1-benzofuran-2-carboxamide	KI	1 nM	US-8748608: 4-phenylpiperazine derivatives with functionalized linkers as dopamine D3 receptor selective ligands and methods of use
N-(Trans-4-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)cyclohexyl)-2-hydroxy-2-methylpropanamide	IC50	1.03 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof
2-{4-[4-(2-Methoxy-phenyl)-piperazin-1-yl]-butyl}-isoindole-1,3-dione	KI	1.25 nM
3-(Trans-4-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)cyclohexyl)-1-methoxy-1-methylurea	IC50	1.29 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof
N-[2-hydroxy-4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-9H-fluorene-2-carboxamide	KI	1.3 nM	US-8748608: 4-phenylpiperazine derivatives with functionalized linkers as dopamine D3 receptor selective ligands and methods of use
N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]-3-hydroxybutyl]-5-methoxy-1-benzofuran-2-carboxamide	KI	1.3 nM	US-8748608: 4-phenylpiperazine derivatives with functionalized linkers as dopamine D3 receptor selective ligands and methods of use
N-[3-hydroxy-4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-1H-indole-2-carboxamide	KI	1.37 nM	US-8748608: 4-phenylpiperazine derivatives with functionalized linkers as dopamine D3 receptor selective ligands and methods of use
2-hydroxy-N-[4-[2-(4-thieno[3,2-c]pyridin-4-ylpiperazin-1-yl)ethyl]cyclohexyl]acetamide	KI	1.4 nM	US-8586579: Anellated pyridine compounds
N-[4-[2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl]cyclohexyl]-1-hydroxycyclopropane-1-carboxamide	KI	1.44 nM	US-8829029: Dual modulators of 5HT2A and D3 receptors
ISOCLOZAPINE	KI	1.45 nM
5-[3-[(5-cyclopentyl-4-methyl-1,2,4-triazol-3-yl)sulfanyl]propyl]-1-[4-(trifluoromethyl)phenyl]-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole	KI	1.48 nM	US-10273244: Substituted hexahydropyrrolo[3,4-b]pyrroles and hexahydrocyclopenta[c]pyrroles as dopamine receptor modulators
7-Methyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinoline-9-carboxylic acid ((2R,5S,10bS)-5-benzyl-10b-hydroxy-2-methyl-3,6-dioxo-octahydro-oxazolo[3,2-a]pyrrolo[2,1-c]pyrazin-2-yl)-amide	KI	1.5 nM
CAS_62865	KI	1.5 nM
N-(Trans-4-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)cyclohexyl)-3-methoxy-3-methylazetidine-1-carboxamide	IC50	1.52 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof
2-((Trans-4-(2-((R)-4-(benzo[b]thiophen-4-yl)-2-methylpiperazin-1-yl)ethyl)cyclohexyl)amino)pyrimidine-5-carbonitrile	IC50	1.58 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof
N-(Trans-4-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)cyclohexyl)-3-hydroxy-3-methylazetidine-1-carboxamide	IC50	1.59 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.92	Ki	0.012	nM	CHEMBL5841759
10.85	Ki	0.014	nM	CHEMBL5918571
10.85	Ki	0.014	nM	CHEMBL5802711
10.80	Ki	0.016	nM	CHEMBL5924177
10.70	Ki	0.02	nM	CHEMBL80919
10.70	Ki	0.02	nM	CHEMBL349426
10.66	Ki	0.022	nM	CHEMBL5833667
10.66	Ki	0.022	nM	CHEMBL5926122
10.60	Ki	0.025	nM	CHEMBL5870203
10.59	EC50	0.026	nM	CHEMBL4285942
10.59	Kd	0.0258	nM	PRAMIPEXOLE
10.59	Kd	0.0258	nM	CHEMBL5207281
10.59	Kd	0.0258	nM	CHEMBL5183205
10.59	Kd	0.0258	nM	CHEMBL5200771
10.59	Kd	0.0258	nM	CHEMBL5204599
10.59	Kd	0.0258	nM	CHEMBL5206565
10.59	Kd	0.0258	nM	CHEMBL5178472
10.59	Kd	0.0258	nM	CHEMBL5208845
10.59	Kd	0.0258	nM	CHEMBL5201074
10.59	Kd	0.0258	nM	CHEMBL5184911
10.59	Kd	0.0258	nM	CHEMBL5180504
10.59	Kd	0.0258	nM	CHEMBL5202592
10.59	Kd	0.0258	nM	CHEMBL5198795
10.59	Kd	0.0258	nM	CHEMBL5176229
10.59	Ki	0.026	nM	CHEMBL6037650
10.57	Ki	0.027	nM	CHEMBL1765633
10.54	Ki	0.029	nM	CHEMBL3905247
10.54	Ki	0.029	nM	CHEMBL5975724
10.52	Kd	0.03	nM	CHEMBL1774386
10.47	Ki	0.034	nM	CHEMBL5949574
10.46	Ki	0.035	nM	CHEMBL5880152
10.46	Ki	0.035	nM	CHEMBL5964833
10.41	Ki	0.039	nM	CHEMBL6060696
10.40	Ki	0.04	nM	BUTACLAMOL
10.40	Kd	0.04	nM	CHEMBL1774386
10.37	Ki	0.043	nM	CHEMBL3966842
10.37	Ki	0.043	nM	CHEMBL3918755
10.37	Ki	0.043	nM	CHEMBL5841988
10.36	Ki	0.044	nM	CHEMBL5875273
10.34	Ki	0.046	nM	CHEMBL3895540
10.33	Ki	0.047	nM	CHEMBL3920252
10.32	Ki	0.048	nM	CHEMBL5787369
10.32	Ki	0.048	nM	CHEMBL5951227
10.30	Ki	0.05	nM	CHEMBL5813094
10.29	Ki	0.051	nM	CHEMBL3932186
10.29	Ki	0.051	nM	CHEMBL5921899
10.28	Ki	0.052	nM	CHEMBL3902496
10.28	Ki	0.052	nM	CHEMBL5817877
10.26	Ki	0.055	nM	CHEMBL3896937
10.25	Ki	0.056	nM	CHEMBL3976282

PubChem BioAssay actives

3738 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[4-[2-(4-phenylpiperazin-1-yl)ethyl]cyclohexyl]quinazolin-4-amine	65285: Binding affinity determined by measuring displacement of [3H]spiperone from cloned Human Dopamine receptor D3 in CHO-K1 cells	ki	<0.0001	uM
N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]imidazo[1,2-a]pyridine-2-carboxamide	1187750: Antagonist activity against human D3R expressed in CHO cells assessed as inhibition of dopamine-induced [35S]GTPgammaS binding by dopamine potency shift assay	ic50	<0.0001	uM
Pramipexole	1895204: Displacement of [3H]N-methylspiperone from human D3 receptor stably expressed in HEK293T cells co-expressing luciferase and CEK incubated for 140 mins by radioligand competition binding based assay	kd	<0.0001	uM
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-N-methylthiophene-2-sulfonamide	1332825: Displacement of [3H]methyl-spiperone from recombinant human D3 receptor expressed in CHO cell membranes after 60 mins by scintillation counting method	ki	<0.0001	uM
N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]-1H-indole-2-carboxamide;hydrochloride	1413596: Agonist activity at human D3 receptor expressed in HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation after 4 hrs by luciferase reporter gene assay	ec50	<0.0001	uM
2-[4-[4-(2,3-difluorophenyl)piperazin-1-yl]butyl]isoindole-1,3-dione	1413596: Agonist activity at human D3 receptor expressed in HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation after 4 hrs by luciferase reporter gene assay	ec50	<0.0001	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-[2-methyl-3-(4-methylphenyl)propyl]urea;bis(2,2,2-trifluoroacetic acid)	1895204: Displacement of [3H]N-methylspiperone from human D3 receptor stably expressed in HEK293T cells co-expressing luciferase and CEK incubated for 140 mins by radioligand competition binding based assay	kd	<0.0001	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-[6-[[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]carbamoylamino]hexyl]urea;tetrakis(2,2,2-trifluoroacetic acid)	1895204: Displacement of [3H]N-methylspiperone from human D3 receptor stably expressed in HEK293T cells co-expressing luciferase and CEK incubated for 140 mins by radioligand competition binding based assay	kd	<0.0001	uM
1-[N’-[3-(2-amino-1,3-thiazol-5-yl)propyl]carbamimidoyl]-3-benzylurea;bis(2,2,2-trifluoroacetic acid)	1895204: Displacement of [3H]N-methylspiperone from human D3 receptor stably expressed in HEK293T cells co-expressing luciferase and CEK incubated for 140 mins by radioligand competition binding based assay	kd	<0.0001	uM
1-[N’-[3-(2-amino-1,3-thiazol-5-yl)propyl]carbamimidoyl]-3-pentylurea;bis(2,2,2-trifluoroacetic acid)	1895204: Displacement of [3H]N-methylspiperone from human D3 receptor stably expressed in HEK293T cells co-expressing luciferase and CEK incubated for 140 mins by radioligand competition binding based assay	kd	<0.0001	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-[1-(3-fluorophenyl)ethyl]urea;dihydrochloride	1895204: Displacement of [3H]N-methylspiperone from human D3 receptor stably expressed in HEK293T cells co-expressing luciferase and CEK incubated for 140 mins by radioligand competition binding based assay	kd	<0.0001	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-(2-methyl-5-phenylpentyl)urea;bis(2,2,2-trifluoroacetic acid)	1895204: Displacement of [3H]N-methylspiperone from human D3 receptor stably expressed in HEK293T cells co-expressing luciferase and CEK incubated for 140 mins by radioligand competition binding based assay	kd	<0.0001	uM
1-[(1R)-1-phenylethyl]-3-[N’-[3-(1H-1,2,4-triazol-5-yl)propyl]carbamimidoyl]urea;dihydrochloride	1895204: Displacement of [3H]N-methylspiperone from human D3 receptor stably expressed in HEK293T cells co-expressing luciferase and CEK incubated for 140 mins by radioligand competition binding based assay	kd	<0.0001	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-hexylurea;bis(2,2,2-trifluoroacetic acid)	1895204: Displacement of [3H]N-methylspiperone from human D3 receptor stably expressed in HEK293T cells co-expressing luciferase and CEK incubated for 140 mins by radioligand competition binding based assay	kd	<0.0001	uM
1-[N’-[3-(2-amino-1,3-thiazol-5-yl)propyl]carbamimidoyl]-3-[2-methyl-3-(4-methylphenyl)propyl]urea;bis(2,2,2-trifluoroacetic acid)	1895204: Displacement of [3H]N-methylspiperone from human D3 receptor stably expressed in HEK293T cells co-expressing luciferase and CEK incubated for 140 mins by radioligand competition binding based assay	kd	<0.0001	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-(2-cyclohexylpropyl)urea;bis(2,2,2-trifluoroacetic acid)	1895204: Displacement of [3H]N-methylspiperone from human D3 receptor stably expressed in HEK293T cells co-expressing luciferase and CEK incubated for 140 mins by radioligand competition binding based assay	kd	<0.0001	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-pentylurea;bis(2,2,2-trifluoroacetic acid)	1895204: Displacement of [3H]N-methylspiperone from human D3 receptor stably expressed in HEK293T cells co-expressing luciferase and CEK incubated for 140 mins by radioligand competition binding based assay	kd	<0.0001	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-benzylurea;bis(2,2,2-trifluoroacetic acid)	1895204: Displacement of [3H]N-methylspiperone from human D3 receptor stably expressed in HEK293T cells co-expressing luciferase and CEK incubated for 140 mins by radioligand competition binding based assay	kd	<0.0001	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-[(1R)-1-phenylethyl]urea;dihydrochloride	1895204: Displacement of [3H]N-methylspiperone from human D3 receptor stably expressed in HEK293T cells co-expressing luciferase and CEK incubated for 140 mins by radioligand competition binding based assay	kd	<0.0001	uM
N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]-7-methoxy-1-benzofuran-2-carboxamide	258948: Displacement of [3H]spiroperidol from cloned human dopamine receptor D3 expressed in CHO cells	ki	0.0001	uM
3-[4-[2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl]cyclohexyl]-1,1-dimethylurea	1332825: Displacement of [3H]methyl-spiperone from recombinant human D3 receptor expressed in CHO cell membranes after 60 mins by scintillation counting method	ki	0.0001	uM
2-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]-3,4-dihydropyrazino[1,2-a]indol-1-one	410333: Displacement of [3H]7OH-DPAT from dopamine D3 receptor expressed in Sf9 cells by scintillation spectrometry	ki	0.0001	uM
2-[4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]phenyl]-1,3-oxazole	1316390: Antagonist activity at human dopamine D3 receptor expressed in CHO cell membranes after 90 mins in presence of quinelorane by [35S]-GTPgammaS binding assay	ki	0.0001	uM
N-[4-(4-naphthalen-1-ylpiperazin-1-yl)butyl]-1H-indole-2-carboxamide	1236117: Displacement of [3H]-N-methylspiperone from human dopamine D3 receptor (unknown origin) expressed in HEK293 cells after 1 hr by liquid scintillation counting	ki	0.0001	uM
N-[4-(4-naphthalen-1-ylpiperazin-1-yl)butyl]-1-benzothiophene-2-carboxamide	1236117: Displacement of [3H]-N-methylspiperone from human dopamine D3 receptor (unknown origin) expressed in HEK293 cells after 1 hr by liquid scintillation counting	ki	0.0001	uM
N-[4-[4-(2-chloro-3-ethylphenyl)piperazin-1-yl]butyl]-1H-indole-2-carboxamide	1629096: Displacement of [3H]N-methylspiperone from human dopamine D3 receptor expressed in HEK293 cell membranes incubated for 1 hr by liquid scintillation counting analysis	ki	0.0001	uM
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]propanamide	1332825: Displacement of [3H]methyl-spiperone from recombinant human D3 receptor expressed in CHO cell membranes after 60 mins by scintillation counting method	ki	0.0001	uM
N-[[4-[[4-(6-chloro-1,2-benzothiazol-3-yl)piperazin-1-yl]methyl]cyclohexyl]methyl]furan-2-carboxamide	1332825: Displacement of [3H]methyl-spiperone from recombinant human D3 receptor expressed in CHO cell membranes after 60 mins by scintillation counting method	ki	0.0001	uM
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]butanamide	1332825: Displacement of [3H]methyl-spiperone from recombinant human D3 receptor expressed in CHO cell membranes after 60 mins by scintillation counting method	ki	0.0001	uM
N-[4-[2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl]cyclohexyl]-3-methoxypropanamide	2026891: Displacement of [3H]N-methylspiperone from human D3 receptor in HEK293 cell membranes measured after 60 mins by scintillation counting method	ki	0.0001	uM
6-(dipropylamino)-5,6,7,8-tetrahydronaphthalen-1-ol	425420: Activity at human dopamine D3 receptor expressed in AtT cells assessed as stimulation of [35S]GTPgammaS binding	ec50	0.0001	uM
6-[2-(4-phenylpiperazin-1-yl)ethyl-propylamino]-5,6,7,8-tetrahydronaphthalen-1-ol	312287: Agonist activity at human cloned dopamine D3 receptor expressed in AtT-20 cells assessed as stimulation of [35S]GTP-gamma-S binding	ec50	0.0001	uM
6-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl-propylamino]-5,6,7,8-tetrahydronaphthalen-1-ol	312287: Agonist activity at human cloned dopamine D3 receptor expressed in AtT-20 cells assessed as stimulation of [35S]GTP-gamma-S binding	ec50	0.0001	uM
6-N-[2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl]-6-N-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine	384700: Agonist activity at human dopamine D3 receptor expressed in mouse ATt-20 cells assessed as stimulation of [35S]GTPgammaS binding	ec50	0.0001	uM
(6S)-6-N-[2-[4-(4-phenylphenyl)piperazin-1-yl]ethyl]-6-N-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine	446402: Agonist activity at human dopamine D3 receptor expressed in mouse AtT-20 cells assessed as stimulation of [35S]GTPgamma binding	ec50	0.0001	uM
6-N-[2-[4-(4-phenylphenyl)piperazin-1-yl]ethyl]-6-N-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine	384700: Agonist activity at human dopamine D3 receptor expressed in mouse ATt-20 cells assessed as stimulation of [35S]GTPgammaS binding	ec50	0.0001	uM
3-[4-[2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl]cyclohexyl]-1,1-dimethylurea;hydrochloride	659797: Binding affinity to human dopamine D3 receptor	ki	0.0001	uM
3-[5-[4-(2,3-dichlorophenyl)piperazin-1-yl]pentoxy]isoquinoline	410333: Displacement of [3H]7OH-DPAT from dopamine D3 receptor expressed in Sf9 cells by scintillation spectrometry	ki	0.0001	uM
N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]isoquinoline-3-carboxamide	410333: Displacement of [3H]7OH-DPAT from dopamine D3 receptor expressed in Sf9 cells by scintillation spectrometry	ki	0.0001	uM
3-[(6aR,9S)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]-1,1-diethylurea	239943: Inhibition constant against [3H]-spiperone binding to human Dopamine receptor D3 expressed in CHO cells	ki	0.0001	uM
5-(3-fluoropropyl)-2,3-dimethoxy-N-[[(2S)-1-prop-2-enylpyrrolidin-2-yl]methyl]benzamide	2141240: Binding affinity to D3 receptor (unknown origin)	ki	0.0002	uM
4-propyl-2,3,4a,5,6,10b-hexahydrobenzo[h][1,4]benzoxazin-9-ol	65147: In vitro binding affinity at human Dopamine receptor D3 expressed in CHO K1 cells was measured by its ability to displace [3H]spiperone	ki	0.0002	uM
N-[4-[4-(2,4-dichlorophenyl)piperazin-1-yl]butyl]-1H-indole-2-carboxamide	410333: Displacement of [3H]7OH-DPAT from dopamine D3 receptor expressed in Sf9 cells by scintillation spectrometry	ki	0.0002	uM
5-bromo-N-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-1H-indole-2-carboxamide	277673: Displacement of [3H]spiperone from human dopamine D3 expressed in CHO cell membrane	ki	0.0002	uM
N-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-4-phenylbenzamide	591963: Displacement of [3H]spiperone from human dopamine D3 receptor expressed in CHO cells after 60 mins	ki	0.0002	uM
1-[4-[2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl]cyclohexyl]-3-methylurea	2026891: Displacement of [3H]N-methylspiperone from human D3 receptor in HEK293 cell membranes measured after 60 mins by scintillation counting method	ki	0.0002	uM
(4aR,10bR)-4-(111C)propyl-2,3,4a,5,6,10b-hexahydrobenzo[h][1,4]benzoxazin-9-ol	539419: Binding affinity to human dopamine D3 receptor expressed in CHO cells	ki	0.0002	uM
N-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]tricyclo[8.2.2.24,7]hexadeca-1(13),4,6,10(14),11,15-hexaene-5-carboxamide	266239: Displacement of [3H]spiperone from human D3 receptor expressed in CHO cells	ki	0.0002	uM
N-[4-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]butyl]-1H-indole-2-carboxamide	1169861: Binding affinity to dopamine D3 receptor (unknown origin)	ki	0.0002	uM
4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]benzamide	1316392: Displacement of [3H]-spiperone from human dopamine D3 receptor expressed in CHO-K1 cell membranes after 90 mins by liquid scintillation counting	ki	0.0002	uM

CTD chemical–gene interactions

48 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
ropinirole	affects binding, increases activity	2
7-(N,N-dipropylamino)-5,6,7,8-tetrahydronaphtho(2,3-b)dihydro-2,3-furan	decreases activity, increases activity, decreases reaction, affects binding	2
nafadotride	affects binding, decreases activity, decreases reaction, increases activity	2
BP 897	affects binding, increases activity, decreases reaction	2
Cocaine	affects response to substance, decreases expression	2
Dopamine	decreases reaction, increases activity, affects binding, increases reaction	2
Spiperone	affects binding, decreases reaction	2
Risperidone	increases response to substance	2
propionaldehyde	decreases expression	1
1,2,3,4-tetrahydroisoquinoline	affects binding	1
fucoxanthin	increases activity	1
7-hydroxy-2-N,N-dipropylaminotetralin	affects binding, increases activity	1
benzo(f)quinoline	affects binding	1
iodosulpride	affects binding, decreases reaction	1
UH 232	decreases activity, affects binding	1
eticlopride	affects binding	1
quinelorane	affects binding, increases activity	1
5-methoxy-1-methyl-2-(n-propylamino)tetralin	decreases activity, affects binding	1
CGS 15855A	increases activity, affects binding	1
3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol	affects binding, increases activity	1
(5,6-dimethoxyindan-2-yl)dipropylamine	affects binding, decreases activity	1
CGP 52608	affects binding, increases reaction	1
A 86929	affects binding	1
3-(4-(4-chlorophenyl-4-hydroxypiperidino)methyl)indole	affects binding, decreases activity	1
GR 218231	affects binding, decreases activity	1
7-methyl-6,7,8,9,14,15-hexahydro-5H-benz(d)indolo(2,3-g)azecine	affects binding	1
sarizotan	affects binding	1
((E)-N-4-(1,2,3,4-tetrahydroisoquinolin-2-yl)butyl)-3-phenylacrylamide	affects binding, decreases activity	1
4-iodo-N-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)cinnamoylamide	affects binding	1
N-(4-(4-(3-aminocarbonyl-phenyl)-piperazin-1-yl)-butyl)-4-bromo-benzamide	affects binding, increases activity	1

ChEMBL screening assays

1359 unique, capped per target: 1088 binding, 262 functional, 6 admet, 3 unclassified

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL670661	Binding	Ratio of binding affinities towards human Dopamine receptor D2 and Dopamine receptor D3 receptors was determined	N-(omega-(4-(2-methoxyphenyl)piperazin-1-yl)alkyl)carboxamides as dopamine D2 and D3 receptor ligands. — J Med Chem
CHEMBL827448	Functional	Dopamine receptor D2/D3 selectivity ratio from in vitro functional assays	Dopamine D3 receptor partial agonists and antagonists as potential drug abuse therapeutic agents. — J Med Chem
CHEMBL4048887	Unclassified	Selectivity ratio of Ki for human dopamine D3 receptor to Ki for human dopamine D4 receptor	1-[3-(4-Butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1) as a Model for the Rational Design of a Novel Class of Brain Penetrant Ligands with High Affinity and Selectivity for Dopamine D4 Receptor. — J Med Chem

Cellosaurus cell lines

3 cell lines: 2 spontaneously immortalized cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1B31	CHO-hD3	Spontaneously immortalized cell line	Female
CVCL_KW88	PathHunter CHO-K1 DRD3 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LA20	PathHunter U2OS DRD3 beta-arrestin	Cancer cell line	Female

Clinical trials (associated diseases)

301 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety