GPR139

Summary

GPR139 (G protein-coupled receptor 139, HGNC:19995) is a protein-coding gene on chromosome 16p12.3, encoding Probable G-protein coupled receptor 139 (Q6DWJ6). Orphan receptor.

This gene encodes a member of the rhodopsin family of G-protein-coupled receptors. The encoded protein is almost exclusively expressed in the central nervous system. L-tryptophan and L-phenylalanine may act as the physiologic ligands of the encoded protein. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 124274 — RefSeq curated summary.

At a glance

• GWAS associations: 24
• Clinical variants (ClinVar): 39 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001002911

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19995
Approved symbol	GPR139
Name	G protein-coupled receptor 139
Location	16p12.3
Locus type	gene with protein product
Status	Approved
Aliases	PGR3
Ensembl gene	ENSG00000180269
Ensembl biotype	protein_coding
OMIM	618448
Entrez	124274

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 nonsense_mediated_decay, 1 protein_coding

ENST00000326571, ENST00000570682

RefSeq mRNA: 2 — MANE Select: NM_001002911 NM_001002911, NM_001318483

CCDS: CCDS32398

Canonical transcript exons

ENST00000570682 — 2 exons

Exon	Start	End
ENSE00002656533	20028239	20032669
ENSE00002668499	20073490	20073890

Expression profiles

Bgee: expression breadth broad, 19 present calls, max score 71.00.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	71.00	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	70.00	silver quality
caudate nucleus	UBERON:0001873	63.36	gold quality
putamen	UBERON:0001874	62.75	gold quality
nucleus accumbens	UBERON:0001882	58.07	gold quality
hypothalamus	UBERON:0001898	52.93	gold quality
bone marrow	UBERON:0002371	42.47	silver quality
colonic epithelium	UBERON:0000397	41.73	gold quality
ventricular zone	UBERON:0003053	39.88	gold quality
substantia nigra	UBERON:0002038	38.59	gold quality
bone marrow cell	CL:0002092	37.93	gold quality
brain	UBERON:0000955	37.44	gold quality
monocyte	CL:0000576	36.13	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.70	gold quality
pituitary gland	UBERON:0000007	35.53	silver quality
leukocyte	CL:0000738	35.36	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	35.12	silver quality
prefrontal cortex	UBERON:0000451	34.59	gold quality
apex of heart	UBERON:0002098	34.57	gold quality
blood	UBERON:0000178	34.25	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
muscle tissue	UBERON:0002385	32.94	silver quality
liver	UBERON:0002107	32.13	gold quality
vermiform appendix	UBERON:0001154	31.93	gold quality
mucosa of stomach	UBERON:0001199	31.59	gold quality
smooth muscle tissue	UBERON:0001135	31.13	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
gall bladder	UBERON:0002110	30.71	gold quality
temporal lobe	UBERON:0001871	30.67	gold quality
amygdala	UBERON:0001876	30.65	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.63

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting GPR139, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-622	98.99	66.48	1050
HSA-MIR-1246	98.54	66.21	959
HSA-MIR-7114-5P	98.51	67.87	1349
HSA-MIR-3139	96.68	66.77	652
HSA-MIR-28-5P	96.16	66.12	579
HSA-MIR-708-5P	96.16	66.12	576
HSA-MIR-4524B-3P	95.52	64.12	964
HSA-MIR-4431	90.07	69.53	39
HSA-MIR-4734	88.28	63.44	87

Literature-anchored findings (GeneRIF, showing 1)

• Molecular cloning of GPRg1, a Gq-coupled orphan receptor that is expressed in the brain. (PMID:15845401)

Cross-species orthologs

138 orthologs

Organism	Symbol	Gene ID
danio_rerio	GPR139	ENSDARG00000109742
mus_musculus	Gpr139	ENSMUSG00000066197
rattus_norvegicus	Gpr139	ENSRNOG00000078864
drosophila_melanogaster	Proc-R	FBGN0029723
drosophila_melanogaster	SPR	FBGN0029768
drosophila_melanogaster	CG15614	FBGN0034168
drosophila_melanogaster	FMRFaR	FBGN0035385
drosophila_melanogaster	CG33639	FBGN0053639
drosophila_melanogaster	CNMaR	FBGN0053696
caenorhabditis_elegans		WBGENE00005748
caenorhabditis_elegans		WBGENE00005749
caenorhabditis_elegans		WBGENE00005750
caenorhabditis_elegans		WBGENE00005751
caenorhabditis_elegans		WBGENE00005753
caenorhabditis_elegans		WBGENE00005754
caenorhabditis_elegans		WBGENE00005755
caenorhabditis_elegans		WBGENE00005756
caenorhabditis_elegans		WBGENE00005757
caenorhabditis_elegans		WBGENE00005758
caenorhabditis_elegans		WBGENE00005759
caenorhabditis_elegans		WBGENE00005760
caenorhabditis_elegans		WBGENE00005761
caenorhabditis_elegans		WBGENE00005762
caenorhabditis_elegans		WBGENE00005763
caenorhabditis_elegans		WBGENE00005764
caenorhabditis_elegans		WBGENE00005766
caenorhabditis_elegans		WBGENE00005767
caenorhabditis_elegans		WBGENE00005768
caenorhabditis_elegans		WBGENE00005769
caenorhabditis_elegans		WBGENE00005770
caenorhabditis_elegans		WBGENE00005771
caenorhabditis_elegans		WBGENE00005773
caenorhabditis_elegans		WBGENE00005776
caenorhabditis_elegans		WBGENE00005778
caenorhabditis_elegans		WBGENE00005779
caenorhabditis_elegans		WBGENE00005780
caenorhabditis_elegans		WBGENE00005781
caenorhabditis_elegans		WBGENE00005782
caenorhabditis_elegans		WBGENE00005785
caenorhabditis_elegans		WBGENE00005787
caenorhabditis_elegans		WBGENE00005788
caenorhabditis_elegans		WBGENE00005789
caenorhabditis_elegans		WBGENE00005790
caenorhabditis_elegans		WBGENE00005791
caenorhabditis_elegans		WBGENE00005795
caenorhabditis_elegans		WBGENE00005798
caenorhabditis_elegans		WBGENE00005800
caenorhabditis_elegans		WBGENE00005801
caenorhabditis_elegans		WBGENE00005802
caenorhabditis_elegans		WBGENE00005803
caenorhabditis_elegans		WBGENE00005804
caenorhabditis_elegans		WBGENE00005806
caenorhabditis_elegans		WBGENE00005807
caenorhabditis_elegans		WBGENE00005808
caenorhabditis_elegans		WBGENE00005809
caenorhabditis_elegans		WBGENE00005810
caenorhabditis_elegans		WBGENE00005813
caenorhabditis_elegans		WBGENE00005814
caenorhabditis_elegans		WBGENE00005815
caenorhabditis_elegans		WBGENE00005816
caenorhabditis_elegans		WBGENE00005818
caenorhabditis_elegans		WBGENE00005820
caenorhabditis_elegans		WBGENE00005823
caenorhabditis_elegans		WBGENE00005824
caenorhabditis_elegans		WBGENE00005826
caenorhabditis_elegans		WBGENE00005829
caenorhabditis_elegans		WBGENE00005830
caenorhabditis_elegans		WBGENE00005831
caenorhabditis_elegans		WBGENE00005832
caenorhabditis_elegans		WBGENE00005834
caenorhabditis_elegans	srw-88	WBGENE00005835
caenorhabditis_elegans		WBGENE00005836
caenorhabditis_elegans		WBGENE00005837
caenorhabditis_elegans		WBGENE00005838
caenorhabditis_elegans		WBGENE00005841
caenorhabditis_elegans		WBGENE00005842
caenorhabditis_elegans		WBGENE00005844
caenorhabditis_elegans		WBGENE00005845
caenorhabditis_elegans		WBGENE00005846
caenorhabditis_elegans		WBGENE00005847
caenorhabditis_elegans		WBGENE00005848
caenorhabditis_elegans		WBGENE00005849
caenorhabditis_elegans		WBGENE00005850
caenorhabditis_elegans		WBGENE00005854
caenorhabditis_elegans		WBGENE00005856
caenorhabditis_elegans	srw-111	WBGENE00005858
caenorhabditis_elegans		WBGENE00005859
caenorhabditis_elegans		WBGENE00005860
caenorhabditis_elegans		WBGENE00005862
caenorhabditis_elegans		WBGENE00005864
caenorhabditis_elegans		WBGENE00005865
caenorhabditis_elegans		WBGENE00005866
caenorhabditis_elegans		WBGENE00005867
caenorhabditis_elegans		WBGENE00005868
caenorhabditis_elegans		WBGENE00005869
caenorhabditis_elegans		WBGENE00005870
caenorhabditis_elegans		WBGENE00005871
caenorhabditis_elegans		WBGENE00005874
caenorhabditis_elegans		WBGENE00005876
caenorhabditis_elegans		WBGENE00005877
caenorhabditis_elegans		WBGENE00005880
caenorhabditis_elegans		WBGENE00005881
caenorhabditis_elegans		WBGENE00005883
caenorhabditis_elegans		WBGENE00005884
caenorhabditis_elegans		WBGENE00005885
caenorhabditis_elegans		WBGENE00005886
caenorhabditis_elegans		WBGENE00005887
caenorhabditis_elegans		WBGENE00005888
caenorhabditis_elegans		WBGENE00005889
caenorhabditis_elegans		WBGENE00005890
caenorhabditis_elegans		WBGENE00005891
caenorhabditis_elegans		WBGENE00008300
caenorhabditis_elegans		WBGENE00010375
caenorhabditis_elegans		WBGENE00010986
caenorhabditis_elegans		WBGENE00012083
caenorhabditis_elegans		WBGENE00015263
caenorhabditis_elegans		WBGENE00015323
caenorhabditis_elegans		WBGENE00016909
caenorhabditis_elegans		WBGENE00017015
caenorhabditis_elegans		WBGENE00017040
caenorhabditis_elegans		WBGENE00017614
caenorhabditis_elegans		WBGENE00017661
caenorhabditis_elegans		WBGENE00019262
caenorhabditis_elegans		WBGENE00019444
caenorhabditis_elegans		WBGENE00019445
caenorhabditis_elegans		WBGENE00019448
caenorhabditis_elegans		WBGENE00020008
caenorhabditis_elegans		WBGENE00020523
caenorhabditis_elegans		WBGENE00020524
caenorhabditis_elegans		WBGENE00020525
caenorhabditis_elegans		WBGENE00022086
caenorhabditis_elegans		WBGENE00022604
caenorhabditis_elegans		WBGENE00022605
caenorhabditis_elegans		WBGENE00022606
caenorhabditis_elegans		WBGENE00045413
caenorhabditis_elegans		WBGENE00189957
caenorhabditis_elegans		WBGENE00194821
caenorhabditis_elegans		WBGENE00303233

Paralogs (1): GPR142 (ENSG00000257008)

Protein

Protein identifiers

Probable G-protein coupled receptor 139 — Q6DWJ6 (reviewed: Q6DWJ6)

Alternative names: G(q)-coupled orphan receptor GPRg1, G-protein-coupled receptor PGR3

All UniProt accessions (3): Q6DWJ6, A0A142CHG1, J3KPI8

UniProt curated annotations — full annotation on UniProt →

Function. Orphan receptor. Seems to act through a G(q/11)-mediated pathway.

Subcellular location. Cell membrane.

Tissue specificity. Expressed almost exclusively in the brain. Detected at very low levels in the peripheral tissues.

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

RefSeq proteins (2): NP_001002911, NP_001305412 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR037486	GPR139	Family
IPR052477	Orphan_GPCR1	Family

Pfam: PF00001

UniProt features (38 total): helix 16, topological domain 8, transmembrane region 7, turn 4, chain 1, glycosylation site 1, strand 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7VUG	ELECTRON MICROSCOPY	3.2
9M42	ELECTRON MICROSCOPY	3.2
7VUH	ELECTRON MICROSCOPY	3.22
7VUI	ELECTRON MICROSCOPY	3.3
7VUJ	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6DWJ6-F1	77.89	0.38

Antibody-complex structures (SAbDab): 4 — 7VUG, 7VUH, 7VUI, 7VUJ

Functional residue map

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

Glycosylation sites (1): 11

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 25 (showing top): GOMF_PEPTIDE_RECEPTOR_ACTIVITY, GOBP_PHOSPHOLIPASE_C_ACTIVATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, chr16p12, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, MEISSNER_NPC_HCP_WITH_H3K27ME3, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, NFKBIA_TARGET_GENES, ZNF274_TARGET_GENES, MIR1299, MIR5700, MIR7114_5P

GO Biological Process (4): G protein-coupled receptor signaling pathway (GO:0007186), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), signal transduction (GO:0007165), neuropeptide signaling pathway (GO:0007218)

GO Molecular Function (3): neuropeptide receptor activity (GO:0008188), identical protein binding (GO:0042802), G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	3
G protein-coupled receptor activity	1
signal transduction	1
phospholipase C activator activity	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
neuropeptide signaling pathway	1
G protein-coupled peptide receptor activity	1
neuropeptide binding	1
protein binding	1
transmembrane signaling receptor activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

604 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR139	GPR149	Q86SP6	625
GPR139	GPR146	Q96CH1	620
GPR139	GPR151	Q8TDV0	573
GPR139	POMC	P01189	547
GPR139	RD3L	P0DJH9	541
GPR139	GPR162	Q16538	519
GPR139	GPRC5B	Q9NZH0	508
GPR139	MRGPRD	Q8TDS7	488
GPR139	MRGPRE	Q86SM8	481
GPR139	GPR152	Q8TDT2	480
GPR139	TRH	P20396	479
GPR139	GPR31	O00270	478
GPR139	GPR148	Q8TDV2	476
GPR139	RRH	O14718	473
GPR139	GPR153	Q6NV75	473

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A2R9YJI3, B2ZHY2, B3DM66, B4XF06, D4A3U0, O02777, O43194, O46635, P08909, P08911, P0C0W8, P14842, P18599, P20272, P21554, P28223, P28335, P32240, P34311, P34968, P35363, P47746, P50128, P50129, P56971, P70259, Q09502, Q333S9, Q5IS53, Q5IS66, Q5IS73, Q5IS98, Q5R4Q6, Q5U431, Q60F97, Q6DWJ6, Q71SP5, Q75Z89, Q801M1, Q80UC8

Diamond homologs: O19037, P0C0W8, P30560, P37288, P47798, P48043, P56444, P56447, Q62463, Q6DWJ6, Q7TQN9, Q7Z601, Q80UC8, Q9WTV8, Q9WTV9, A3KFT3, A6NM03, O42329, O73810, O77808, O88721, O88855, P0C0L6, P21917, P30518, P30559, P32251, P32306, P32307, P47901, P48044, P48974, P53453, P56449, P56494, P59922, P70536, P97266, P97926, Q00788

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

419 predictions. Top by Δscore:

Variant	Effect	Δscore
16:20032665:ATTTG:A	acceptor_gain	1.0000
16:20032666:TTTG:T	acceptor_gain	1.0000
16:20032667:TTG:T	acceptor_gain	1.0000
16:20032668:TG:T	acceptor_gain	1.0000
16:20032668:TGCTG:T	acceptor_loss	1.0000
16:20032670:C:CA	acceptor_loss	1.0000
16:20032670:C:CC	acceptor_gain	1.0000
16:20032671:T:C	acceptor_loss	1.0000
16:20073484:CCTCA:C	donor_loss	0.9800
16:20073485:CTCAC:C	donor_loss	0.9800
16:20073486:TCA:T	donor_loss	0.9800
16:20073487:CACC:C	donor_loss	0.9800
16:20032667:TTGC:T	acceptor_gain	0.9700
16:20032668:TGCT:T	acceptor_gain	0.9700
16:20032669:GCTGT:G	acceptor_gain	0.9700
16:20073566:C:CT	donor_gain	0.9700
16:20032670:CTGT:C	acceptor_gain	0.9600
16:20032672:G:C	acceptor_gain	0.9600
16:20032667:T:C	acceptor_gain	0.9500
16:20032672:G:GC	acceptor_gain	0.9500
16:20032666:TTTGC:T	acceptor_gain	0.9300
16:20038591:A:T	donor_gain	0.9000
16:20073567:C:CT	donor_gain	0.9000
16:20032671:T:G	acceptor_gain	0.8400
16:20051733:TCCA:T	donor_gain	0.8400
16:20041690:TCCCC:T	acceptor_gain	0.8300
16:20066979:A:C	donor_gain	0.8000
16:20073634:C:A	donor_gain	0.7500
16:20038931:ACTG:A	donor_gain	0.7200
16:20038932:CTGC:C	donor_gain	0.7200

AlphaMissense

2330 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:20031921:G:C	F292L	1.000
16:20031921:G:T	F292L	1.000
16:20031923:A:G	F292L	1.000
16:20032579:T:A	D73V	1.000
16:20032579:T:G	D73A	1.000
16:20031922:A:C	F292C	0.999
16:20031922:A:G	F292S	0.999
16:20031954:G:C	N281K	0.999
16:20031954:G:T	N281K	0.999
16:20032069:G:C	P243R	0.999
16:20032076:A:G	W241R	0.999
16:20032076:A:T	W241R	0.999
16:20032086:A:C	F237L	0.999
16:20032086:A:T	F237L	0.999
16:20032088:A:G	F237L	0.999
16:20032213:G:C	P195R	0.999
16:20032213:G:T	P195H	0.999
16:20032317:G:C	S160R	0.999
16:20032317:G:T	S160R	0.999
16:20032319:T:G	S160R	0.999
16:20032408:A:T	V130D	0.999
16:20032411:G:T	A129D	0.999
16:20032419:C:A	R126S	0.999
16:20032419:C:G	R126S	0.999
16:20032420:C:A	R126M	0.999
16:20032423:T:A	D125V	0.999
16:20032423:T:G	D125A	0.999
16:20032448:A:G	W117R	0.999
16:20032448:A:T	W117R	0.999
16:20032453:G:A	S115F	0.999

dbSNP variants (sampled 300 via entrez): RS1000067567 (16:20073342 C>A,G), RS1000101837 (16:20036865 A>G), RS1000112063 (16:20032585 G>A), RS1000169739 (16:20033944 A>G), RS1000303561 (16:20055567 C>T), RS1000387469 (16:20043226 A>G), RS1000398834 (16:20032361 G>A,T), RS1000428912 (16:20049751 A>G), RS1000652392 (16:20055966 CA>C), RS1000829690 (16:20044526 G>A), RS1000848688 (16:20066122 C>T), RS1000854422 (16:20054537 A>G), RS1000871363 (16:20048888 G>T), RS1000935443 (16:20052372 G>T), RS1000967075 (16:20054829 G>A)

Disease associations

OMIM: gene MIM:618448 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST003177_37	Childhood body mass index	4.000000e-06
GCST004495_130	BMI (adjusted for smoking behaviour)	2.000000e-09
GCST004495_131	BMI (adjusted for smoking behaviour)	1.000000e-10
GCST004497_102	Body mass index (joint analysis main effects and smoking interaction)	3.000000e-11
GCST004497_103	Body mass index (joint analysis main effects and smoking interaction)	7.000000e-08
GCST004498_15	BMI in smokers	2.000000e-06
GCST004499_40	BMI in non-smokers	4.000000e-07
GCST004499_64	BMI in non-smokers	3.000000e-06
GCST004904_181	Body mass index	1.000000e-17
GCST004904_97	Body mass index	8.000000e-12
GCST005146_33	Birth weight	3.000000e-09
GCST006190_84	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	6.000000e-08
GCST006191_2	Diastolic blood pressure x smoking status (ever vs never) interaction (1df test)	2.000000e-08
GCST007485_15	Anthropometric traits	1.000000e-07
GCST007490_24	Anthropometric traits (multi-trait analysis)	2.000000e-15
GCST007490_25	Anthropometric traits (multi-trait analysis)	1.000000e-16
GCST007804_1	Sleep (number of episodes)	6.000000e-14
GCST008140_1	Metabolic syndrome	3.000000e-06
GCST008151_31	Waist circumference	4.000000e-06
GCST008158_53	Body mass index	7.000000e-11
GCST008160_76	Waist circumference	4.000000e-06
GCST008362_85	Birth weight	6.000000e-09
GCST010988_36	Adult body size	3.000000e-18
GCST90000025_87	Appendicular lean mass	2.000000e-16

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004318	smoking behavior
EFO:0004344	birth weight
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0004324	body weights and measures
EFO:0004338	body weight
EFO:0000195	metabolic syndrome
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3632455 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,434 (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
CHEMBL214332	INTERMEDINE	2	2,391
CHEMBL4779773	ZELATRIAZIN	2	43

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Class A Orphans with emerging pharmacology

Most potent curated ligand interactions (8 total), top 8:

Ligand	Action	Affinity	Parameter
JNJ-63533054	Agonist	7.62	pKi
compound 1a [PMID: 24900311]	Full agonist	7.41	pEC50
zelatriazin (TAK-041)	Agonist	6.92	pKi
NCRW0005-F05	Antagonist	6.68	pIC50
NCRW0105-E06	Antagonist	6.29	pIC50
LP-471756	Antagonist	6.19	pIC50
L-tryptophan	Agonist	3.13	pKi
L-phenylalanine	Agonist	3.06	pKi

Binding affinities (BindingDB)

104 measured of 104 human assays (104 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(s)-2-(6,8-dimethyl-4-oxobenzo[d][1,2,3]triazin-3(4h)-yl)-n-(1-p-tolylethyl)acetamide	KI	10 nM	US-9556130: 4-oxo-3,4-dihydro-1,2,3-benzotriazine modulators of GPR139
(s)—n-(1-(2-fluoro-4-(trifluoromethyl)phenyl)ethyl)-2-(5-methoxy-4-oxobenzo[d][1,2,3]triazin-3(4h)-yl)acetamide	KI	11 nM	US-9556130: 4-oxo-3,4-dihydro-1,2,3-benzotriazine modulators of GPR139
Preparation of (S)-2-(6-methyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)-N-(1-phenylethyl)acetamide	EC50	13 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
Preparation of (S)—N-1-(4-bromophenyl)ethyl-2-(6-methyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)acetamide	EC50	15 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
Preparation of (S)—N-(1-(4-fluorophenyl)ethyl-2-(6-methyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)acetamide	EC50	19 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
Preparation of (S)-2-(6,8-dimethyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)-N-(1-phenylethyl)acetamide	EC50	19 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
Preparation of (S)-2-(6-methyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)-N-(1-(p-tolyl)ethyl)acetamide	EC50	21 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
Preparation of (S)-2 (6-methyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)-N-(1-phenylpropyl)acetamide	EC50	22 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
Preparation of (S)—N-1-(4-chlorophenyl)ethyl-2-(6-methyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)acetamide	EC50	23 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
Preparation of (S)—N-(1-(naphthalen-1-ethyl)-2-(4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)acetamide	EC50	23 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
Preparation of (S)—N-(1-(4-methoxyphenyl)ethyl-2-(6-methyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)acetamide	EC50	24 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
Preparation of (S)-2-(4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)-N-(1-(4-(trifluoromethoxy)phenyl)ethyl)acetamide	EC50	25 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
(s)-2-(6,8-dichloro-4-oxobenzo[d][1,2,3]triazin-3(4h)-yl)-n-(1-p-tolylethyl)acetamide	KI	26 nM	US-9556130: 4-oxo-3,4-dihydro-1,2,3-benzotriazine modulators of GPR139
(s)-2-(5-methoxy-4-oxobenzo[d][1,2,3]triazin-3 (4h)-yl)-n-(1-(4-(trifluoromethyl)phenyl)ethyl)acetamide	KI	26 nM	US-9556130: 4-oxo-3,4-dihydro-1,2,3-benzotriazine modulators of GPR139
Preparation of (S)—N-(1-(4-fluorophenyl)-2-methylpropyl)-2-(6-methyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)acetamide	EC50	26 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
Preparation of (S)-2-(4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)-N-(1-(p-tolyl)ethyl)acetamide	EC50	28 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
Preparation of (S)—N-1-(4-chlorophenyl)ethyl-2-(4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)acetamide	EC50	30 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
(s)-2-(5-methoxy-4-oxobenzo[d][1,2,3]triazin-3(4h)-yl)-n-(1-(4-(trifluoromethoxy)phenyl)ethyl)acetamide	KI	33 nM	US-9556130: 4-oxo-3,4-dihydro-1,2,3-benzotriazine modulators of GPR139
(s)—n-(1-(2-fluoro-4-(trifluoromethoxy)phenyl)ethyl)-2-(5-methoxy-4-oxobenzo[d][1,2,3]triazin-3(4h)-yl)acetamide	KI	33 nM	US-9556130: 4-oxo-3,4-dihydro-1,2,3-benzotriazine modulators of GPR139
Preparation of (S)—N-(1-(4-bromophenyl)ethyl-2-(4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)acetamide	EC50	33 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
Preparation of (S)-2-(6,8-dimethyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)-N-(1-(4-methoxyphenyl)ethyl)acetamide	EC50	34 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
(s)—n-(1-(2,4-dimethylphenyl)ethyl)-2-(6-fluoro-4-oxobenzo[d][1,2,3]triazin-3(4h)-yl)acetamide	KI	39 nM	US-9556130: 4-oxo-3,4-dihydro-1,2,3-benzotriazine modulators of GPR139
(s)-2-(6-fluoro-4-oxobenzo[d][1,2,3]triazin-3(4h)-yl)-n-(1-(4-(trifluoromethoxy)phenyl)ethyl)acetamide	KI	42 nM	US-9556130: 4-oxo-3,4-dihydro-1,2,3-benzotriazine modulators of GPR139
Preparation of (S)-2-(6-methyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)-N-(1-naphthalen-1-yl)ethyl)acetamide	EC50	42 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
Preparation of (S)-2-(4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)-N-(1-phenylpropyl)acetamide	EC50	45 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
(s)-2-(5-methoxy-4-oxobenzo[d][1,2,3]triazin-3(4h)-yl)-n-(1-p-tolylethyl)acetamide	KI	48 nM	US-9556130: 4-oxo-3,4-dihydro-1,2,3-benzotriazine modulators of GPR139
Preparation of (S)—N-(1-(4-fluorophenyl)ethyl-2-(4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)acetamide	EC50	56 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
Preparation of (S)—N-1-(4-chlorophenyl)ethyl-2-(6,8-dimethyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)acetamide	EC50	56 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
Preparation of (S)—N-(2-methyl-1-phenylpropyl)-2-(4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)acetamide	EC50	57 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
(s)-2-(6-methoxy-4-oxobenzo[d][1,2,3]triazin-3(4h)-yl)-n-(1-p-tolylethyl)acetamide	KI	58 nM	US-9556130: 4-oxo-3,4-dihydro-1,2,3-benzotriazine modulators of GPR139
Preparation of (S)—N-(1-(4-methoxyphenyl)ethyl)-2-(4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)acetamide	EC50	60 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
Preparation of (S)-2-(4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)-N-(1-(4-(trifluoromethyl)phenyl)ethyl)acetamide	EC50	61 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
Preparation of (S)—N-(2-methyl-1-(4-trifluoromethyl)phenylpropyl)-2-(4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)acetamide	EC50	61 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
(s)—n-(1-(2,4-dimethylphenyl)ethyl)-2-(4-oxobenzo[d][1,2,3]triazin-3(4h)-yl)acetamide	KI	63 nM	US-9556130: 4-oxo-3,4-dihydro-1,2,3-benzotriazine modulators of GPR139
2-(6-methyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3-yl)-N-[(1S)-1-[4-(trifluoromethyl)phenyl]ethyl]acetamide	EC50	68 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
(s)-2-(8-methyl-4-oxobenzo[d][1,2,3]triazin-3(4h)-yl)-n-(1-p-tolylethyl)acetamide	KI	72 nM	US-9556130: 4-oxo-3,4-dihydro-1,2,3-benzotriazine modulators of GPR139
Preparation of (S)-2-(6-methyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)-N-(1-(4-(trifluoromethoxy)phenyl)ethyl)acetamide	EC50	75 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
(s)—n-(1-(2-fluoro-4-methylphenyl)ethyl)-2-(6-fluoro-4-oxobenzo[d][1,2,3]triazin-3(4h)-yl)acetamide	KI	77 nM	US-9556130: 4-oxo-3,4-dihydro-1,2,3-benzotriazine modulators of GPR139
(s)-2-(8-fluoro-6-methyl-4-oxobenzo[d][1,2,3]triazin-3(4h)-yl)-n-(1-(p-tolyl)ethyl)acetamide	KI	85 nM	US-9556130: 4-oxo-3,4-dihydro-1,2,3-benzotriazine modulators of GPR139
(s)-2-(5-methyl-4-oxobenzo[d][1,2,3]triazin-3 (4h)-yl)-n-(1-p-tolylethyl)acetamide	KI	92 nM	US-9556130: 4-oxo-3,4-dihydro-1,2,3-benzotriazine modulators of GPR139
(s)—n-(1-(2-fluoro-4-(trifluoromethoxy)phenyl)ethyl)-2-(6-fluoro-4-oxobenzo[d][1,2,3]triazin-3(4h)-yl)acetamide	KI	93 nM	US-9556130: 4-oxo-3,4-dihydro-1,2,3-benzotriazine modulators of GPR139
Preparation of (S)-2-(6,8-dimethyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)-N-(1-(p-tolyl)ethyl)acetamide	EC50	93 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
Preparation of (S)-2-(6,8-dimethyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)-N-(1-(4-fluorophenyl)ethyl)acetamide	EC50	95 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
Preparation of (S)-2-(6,8-dimethyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)-N-(1-(4-(trifluoromethoxy)phenyl)ethyl)acetamide	EC50	96 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
(s)-2-(6-fluoro-4-oxobenzo[d][1,2,3]triazin-3(4h)-yl)-n-(1-(4-(trifluoromethyl)phenyl)ethyl)acetamide	KI	106 nM	US-9556130: 4-oxo-3,4-dihydro-1,2,3-benzotriazine modulators of GPR139
(s)-2-(8-chloro-4-oxobenzo[d][1,2,3]triazin-3(4h)-yl)-n-(1-p-tolylethyl)acetamide	KI	110 nM	US-9556130: 4-oxo-3,4-dihydro-1,2,3-benzotriazine modulators of GPR139
Preparation of (S)-2-(4-oxopyrrolo[1,2-d][1,2,4]triazin-3(4H)yl)-N-(1-phenylethyl)acetamide	EC50	111 nM	US-20250163065: PYRROLOTRIAZINONE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
(s)-2-(6-methoxy-4-oxobenzo[d][1,2,3]triazin-3(4h)-yl)-n-(1-(4-(trifluoromethyl)phenyl)ethyl)acetamide	KI	115 nM	US-9556130: 4-oxo-3,4-dihydro-1,2,3-benzotriazine modulators of GPR139
N-[2-(2-chloro-4-methoxyphenyl)ethyl]-2-(4-oxo-1,2,3-benzotriazin-3-yl)acetamide	KI	117 nM	US-9556130: 4-oxo-3,4-dihydro-1,2,3-benzotriazine modulators of GPR139
(s)-2-(4-oxobenzo[d][1,2,3]triazin-3(4h)-yl)-n-(1-(4-(trifluoromethoxy)phenyl)ethyl)acetamide	KI	119 nM	US-9556130: 4-oxo-3,4-dihydro-1,2,3-benzotriazine modulators of GPR139

ChEMBL bioactivities

681 potent at pChembl≥5 of 690 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	EC50	1	nM	CHEMBL4789123
9.00	EC50	1	nM	CHEMBL4762957
9.00	EC50	1	nM	CHEMBL4781404
9.00	EC50	1	nM	CHEMBL4785963
9.00	EC50	1	nM	CHEMBL4759611
9.00	EC50	1	nM	CHEMBL4748681
9.00	EC50	1	nM	CHEMBL4786371
9.00	EC50	1	nM	CHEMBL4757480
9.00	EC50	1	nM	CHEMBL4753587
9.00	EC50	1	nM	CHEMBL4745096
9.00	EC50	1	nM	CHEMBL4796254
9.00	EC50	1	nM	CHEMBL4792732
9.00	EC50	1	nM	CHEMBL4760528
9.00	EC50	1	nM	CHEMBL4792356
9.00	EC50	1	nM	CHEMBL4754476
9.00	EC50	1	nM	CHEMBL4798509
9.00	EC50	1	nM	CHEMBL4762121
9.00	EC50	1	nM	CHEMBL4790080
9.00	EC50	1	nM	CHEMBL4750718
9.00	EC50	1	nM	CHEMBL4746822
9.00	EC50	1	nM	CHEMBL4740519
9.00	EC50	1	nM	CHEMBL4740228
9.00	EC50	1	nM	CHEMBL4746108
9.00	EC50	1	nM	CHEMBL4763362
9.00	EC50	1	nM	CHEMBL4745668
9.00	EC50	1	nM	CHEMBL4757619
9.00	EC50	1	nM	CHEMBL4783815
9.00	EC50	1	nM	CHEMBL4791843
9.00	EC50	1	nM	CHEMBL4754384
9.00	EC50	1	nM	CHEMBL4756937
9.00	EC50	1	nM	CHEMBL4745432
9.00	EC50	1	nM	CHEMBL4787308
9.00	EC50	1	nM	CHEMBL4784153
9.00	EC50	1	nM	CHEMBL4760812
9.00	EC50	1	nM	CHEMBL4744169
9.00	EC50	1	nM	CHEMBL4792515
9.00	EC50	1	nM	CHEMBL4757742
9.00	EC50	1	nM	CHEMBL4751886
9.00	EC50	1	nM	CHEMBL4799144
9.00	EC50	1	nM	CHEMBL4751720
9.00	EC50	1	nM	CHEMBL4800487
9.00	EC50	1	nM	CHEMBL4797724
9.00	EC50	1	nM	CHEMBL4747431
9.00	EC50	1	nM	CHEMBL4749705
9.00	EC50	1	nM	CHEMBL4764666
9.00	EC50	1	nM	CHEMBL4740491
9.00	EC50	1	nM	CHEMBL4759991
9.00	EC50	1	nM	CHEMBL4793463
9.00	EC50	1	nM	CHEMBL4757506
9.00	EC50	1	nM	CHEMBL4791551

PubChem BioAssay actives

226 with measured affinity, of 355 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-[(1S)-1-(4-chloro-3-fluorophenyl)ethyl]-2-(4-oxothieno[2,3-d]pyridazin-5-yl)acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0087	uM
N-[(1S)-1-(4-bromophenyl)ethyl]-2-(4-oxo-1,2,3-benzotriazin-3-yl)acetamide	1751499: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay	ec50	0.0090	uM
2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3-yl)-N-[(1S)-1-(4-methylphenyl)ethyl]acetamide	1751499: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay	ec50	0.0100	uM
2-(6-fluoro-4-oxo-1,2,3-benzotriazin-3-yl)-N-[(1S)-1-(4-methylphenyl)ethyl]acetamide	1751499: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay	ec50	0.0110	uM
2-(6-methyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3-yl)-N-[(1S)-1-phenylethyl]acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0126	uM
N-[(1S)-1-(3,4-dichlorophenyl)ethyl]-2-(4-oxothieno[2,3-d]pyridazin-5-yl)acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0135	uM
2-(8-fluoro-6-methyl-4-oxo-1,2,3-benzotriazin-3-yl)-N-[(1S)-1-(4-methylphenyl)ethyl]acetamide	1751499: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay	ec50	0.0150	uM
2-(4-oxo-1,2,3-benzotriazin-3-yl)-N-[(1S)-1-[4-(trifluoromethyl)phenyl]ethyl]acetamide	1751499: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay	ec50	0.0150	uM
3-chloro-N-[2-oxo-2-[[(1S)-1-phenylethyl]amino]ethyl]benzamide	1255328: Agonist activity at human GPR139 receptor expressed in HEK293 cells assessed as calcium mobilization by FLIPR assay	ec50	0.0160	uM
N-[(1S)-1-(4-methylphenyl)ethyl]-2-(4-oxothieno[2,3-d]pyridazin-5-yl)acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0178	uM
N-[(1S)-1-[4-(difluoromethoxy)phenyl]ethyl]-2-(4-oxo-1,2,3-benzotriazin-3-yl)acetamide	1751499: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay	ec50	0.0180	uM
N-[(1S)-1-(4-bromophenyl)ethyl]-2-(6-methyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3-yl)acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0182	uM
N-[(1S)-1-(4-fluorophenyl)ethyl]-2-(6-methyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3-yl)acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0186	uM
N-[(1S)-1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl]-2-(4-oxo-1,2,3-benzotriazin-3-yl)acetamide	1751499: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay	ec50	0.0190	uM
2-(7-methoxy-4-oxo-1,2,3-benzotriazin-3-yl)-N-[(1S)-1-(4-methylphenyl)ethyl]acetamide	1751499: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay	ec50	0.0190	uM
2-(6,8-dimethyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3-yl)-N-[(1S)-1-phenylethyl]acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0191	uM
2-(6-methyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3-yl)-N-[(1S)-1-(4-methylphenyl)ethyl]acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0195	uM
N-[(1S)-1-(4-bromophenyl)ethyl]-2-(4-oxothieno[2,3-d]pyridazin-5-yl)acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0209	uM
N-[(1S)-1-[4-(difluoromethoxy)phenyl]ethyl]-2-(5-methoxy-4-oxo-1,2,3-benzotriazin-3-yl)acetamide	1751499: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay	ec50	0.0210	uM
N-[2-(4-chlorophenyl)ethyl]-2-(4-oxo-1,2,3-benzotriazin-3-yl)acetamide	1751499: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay	ec50	0.0210	uM
N-[(1S)-1-(4-methylphenyl)ethyl]-2-(4-oxothieno[2,3-d]triazin-3-yl)acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0214	uM
2-(6-methyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3-yl)-N-[(1S)-1-phenylpropyl]acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0214	uM
N-[(1S)-1-(4-chlorophenyl)ethyl]-2-(4-oxothieno[2,3-d]triazin-3-yl)acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0219	uM
N-[(1S)-1-(4-chlorophenyl)ethyl]-2-(6-methyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3-yl)acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0219	uM
2-(4-oxo-1,2,3-benzotriazin-3-yl)-N-[(1S)-1-[4-(trifluoromethoxy)phenyl]ethyl]acetamide	1751499: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay	ec50	0.0220	uM
2-(5-methoxy-4-oxo-1,2,3-benzotriazin-3-yl)-N-[(1S)-1-[4-(trifluoromethoxy)phenyl]ethyl]acetamide	1751499: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay	ec50	0.0220	uM
N-[(1S)-1-(4-chlorophenyl)ethyl]-2-(4-oxo-1,2,3-benzotriazin-3-yl)acetamide	1751499: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay	ec50	0.0220	uM
N-[(1S)-1-(2-chloro-4-fluorophenyl)ethyl]-2-(4-oxothieno[2,3-d]pyridazin-5-yl)acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0224	uM
N-[(1S)-1-(4-chlorophenyl)ethyl]-2-(4-oxothieno[2,3-d]pyridazin-5-yl)acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0229	uM
N-[(1S)-1-(4-methoxyphenyl)ethyl]-2-(6-methyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3-yl)acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0234	uM
N-[(1S)-1-(2-fluoro-4-methylphenyl)ethyl]-2-(4-oxo-1,2,3-benzotriazin-3-yl)acetamide	1751499: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay	ec50	0.0240	uM
2-(5-methoxy-4-oxo-1,2,3-benzotriazin-3-yl)-N-[(1S)-1-(4-methylphenyl)ethyl]acetamide	1751499: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay	ec50	0.0240	uM
3-chloro-5-fluoro-N-[2-oxo-2-[[(1S)-1-phenylethyl]amino]ethyl]benzamide	1255328: Agonist activity at human GPR139 receptor expressed in HEK293 cells assessed as calcium mobilization by FLIPR assay	ec50	0.0240	uM
N-[(1S)-1-(4-methylphenyl)propyl]-2-(4-oxo-1,2,3-benzotriazin-3-yl)acetamide	1751499: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay	ec50	0.0240	uM
N-[(1S)-1-(2-methylphenyl)ethyl]-2-(4-oxo-1,2,3-benzotriazin-3-yl)acetamide	1751499: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay	ec50	0.0240	uM
3-methyl-N-[2-oxo-2-[[(1S)-1-phenylethyl]amino]ethyl]benzamide	1255328: Agonist activity at human GPR139 receptor expressed in HEK293 cells assessed as calcium mobilization by FLIPR assay	ec50	0.0240	uM
N-[(1S)-1-(3,4-difluorophenyl)ethyl]-2-(4-oxothieno[2,3-d]pyridazin-5-yl)acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0245	uM
N-[(1S)-1-(2,4-dimethylphenyl)ethyl]-2-(4-oxo-1,2,3-benzotriazin-3-yl)acetamide	1751499: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay	ec50	0.0270	uM
N-[(1S)-1-(2,4-difluorophenyl)ethyl]-2-(4-oxothieno[2,3-d]pyridazin-5-yl)acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0275	uM
N-[(1S)-1-(4-methylphenyl)ethyl]-2-(4-oxopyrrolo[1,2-d][1,2,4]triazin-3-yl)acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0275	uM
N-[(1S)-1-naphthalen-1-ylethyl]-2-(4-oxopyrrolo[1,2-d][1,2,4]triazin-3-yl)acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0275	uM
N-[(1S)-1-naphthalen-1-ylethyl]-2-(4-oxothieno[2,3-d]pyridazin-5-yl)acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0275	uM
2-(4-oxothieno[2,3-d]pyridazin-5-yl)-N-[(1S)-1-[4-(trifluoromethyl)phenyl]ethyl]acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0282	uM
N-[(1S)-1-(4-chlorophenyl)ethyl]-2-(4-oxopyrrolo[1,2-d][1,2,4]triazin-3-yl)acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0282	uM
N-[(1S)-1-[2-fluoro-4-(trifluoromethoxy)phenyl]ethyl]-2-(4-oxo-1,2,3-benzotriazin-3-yl)acetamide	1751499: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay	ec50	0.0290	uM
N-[(1S)-1-(4-methylphenyl)ethyl]-2-(4-oxo-1,2,3-benzotriazin-3-yl)acetamide	1751499: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay	ec50	0.0300	uM
2-(8-methoxy-4-oxo-1,2,3-benzotriazin-3-yl)-N-[(1S)-1-(4-methylphenyl)ethyl]acetamide	1751499: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay	ec50	0.0300	uM
N-[2-(4-methylphenyl)ethyl]-2-(4-oxo-1,2,3-benzotriazin-3-yl)acetamide	1751499: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay	ec50	0.0300	uM
N-[(1S)-1-(4-methylphenyl)ethyl]-2-(4-oxo-1,2,3-benzotriazin-3-yl)propanamide	1751499: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay	ec50	0.0300	uM
N-[(1S)-1-(4-fluorophenyl)-2-methylpropyl]-2-(6-methyl-4-oxopyrrolo[1,2-d][1,2,4]triazin-3-yl)acetamide	2019852: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis	ec50	0.0309	uM

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Vanadium	increases abundance, increases methylation	1
Metals, Heavy	increases abundance, increases methylation	1
Cadmium Chloride	increases expression	1

ChEMBL screening assays

19 unique, capped per target: 11 functional, 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3637279	Functional	Agonist activity at human GPR139 receptor expressed in HEK293 cells assessed as calcium mobilization by FLIPR assay	Identification and SAR of Glycine Benzamides as Potent Agonists for the GPR139 Receptor. — ACS Med Chem Lett
CHEMBL3637304	Binding	Total binding affinity to human GPR139 receptor expressed in CHO-TRex cells at 10 nM after 60 mins by scintillation counting	Identification and SAR of Glycine Benzamides as Potent Agonists for the GPR139 Receptor. — ACS Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KX32	PathHunter CHO-K1 GPR139 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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