HCAR3

Summary

HCAR3 (hydroxycarboxylic acid receptor 3, HGNC:16824) is a protein-coding gene on chromosome 12q24.31, encoding Hydroxycarboxylic acid receptor 3 (P49019). G-protein coupled receptor for 3-hydroxyoctanoate, a fatty acid beta-oxidation intermediate.

Predicted to enable GTP binding activity; nicotinic acid receptor activity; and purinergic nucleotide receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in cell junction.

Source: NCBI Gene 8843 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 63 total — 1 pathogenic
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• MANE Select transcript: NM_006018

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16824
Approved symbol	HCAR3
Name	hydroxycarboxylic acid receptor 3
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Aliases	HCA3, HM74
Ensembl gene	ENSG00000255398
Ensembl biotype	protein_coding
OMIM	606039
Entrez	8843

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000528880

RefSeq mRNA: 1 — MANE Select: NM_006018 NM_006018

CCDS: CCDS53842

Canonical transcript exons

ENST00000528880 — 1 exons

Exon	Start	End
ENSE00002172588	122714756	122716811

Expression profiles

Bgee: expression breadth ubiquitous, 102 present calls, max score 94.41.

FANTOM5 (CAGE): breadth broad, TPM avg 10.5675 / max 3231.0853, expressed in 314 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133840	10.5675	314

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	94.41	gold quality
granulocyte	CL:0000094	90.34	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.25	gold quality
leukocyte	CL:0000738	80.49	gold quality
spleen	UBERON:0002106	80.10	gold quality
monocyte	CL:0000576	79.66	gold quality
esophagus mucosa	UBERON:0002469	79.08	gold quality
lower esophagus mucosa	UBERON:0035834	78.62	gold quality
bone marrow	UBERON:0002371	78.13	gold quality
skin of abdomen	UBERON:0001416	77.21	gold quality
zone of skin	UBERON:0000014	75.72	gold quality
skin of leg	UBERON:0001511	74.52	gold quality
vermiform appendix	UBERON:0001154	71.01	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	70.91	gold quality
bone marrow cell	CL:0002092	70.24	gold quality
placenta	UBERON:0001987	67.87	gold quality
omental fat pad	UBERON:0010414	65.71	gold quality
upper lobe of left lung	UBERON:0008952	65.52	gold quality
adipose tissue	UBERON:0001013	63.76	gold quality
subcutaneous adipose tissue	UBERON:0002190	61.82	gold quality
lung	UBERON:0002048	61.76	gold quality
thoracic mammary gland	UBERON:0005200	61.44	gold quality
tonsil	UBERON:0002372	60.14	gold quality
vagina	UBERON:0000996	59.79	gold quality
urinary bladder	UBERON:0001255	59.73	gold quality
gall bladder	UBERON:0002110	57.28	gold quality
right lung	UBERON:0002167	56.72	gold quality
esophagus	UBERON:0001043	56.53	gold quality
saliva-secreting gland	UBERON:0001044	55.83	gold quality
minor salivary gland	UBERON:0001830	55.70	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARG

miRNA regulators (miRDB)

27 targeting HCAR3, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-4326	98.97	67.63	962
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-3927-5P	94.90	68.11	399
HSA-MIR-1295A	85.69	62.42	75

Literature-anchored findings (GeneRIF, showing 15)

• HM74 is highly expressed in adipose tissue and is a nicotinic acid receptor (PMID:12563315)
• These results suggest that aromatic D-amino acids elicit a chemotactic response in human neutrophils via activation of GPR109B. (PMID:19237584)
• An A allele in HM74 was significantly associated with schizophrenia and with schizophrenia plus bipolar disorder combined. (PMID:19502010)
• the ligand receptor pair 3-OH-octanoic acid/GPR109B mediates a negative feedback regulation of adipocyte lipolysis in human but not in mouse (PMID:19561068)
• Data show that the coordinated PPARgamma-mediated regulation of the GPR81, GPR109A and GPR109B presents a novel mechanism by which TZDs may reduce circulating free fatty acid levels and perhaps ameliorate insulin resistance in obese patients. (PMID:19633298)
• these results demonstrate that GPR109A and GPR109B dimerization is a constitutive process occurring early during biosynthesis. (PMID:20380810)
• In contrast, in a squamous cell carcinoma derived cell line, both GPR109A and GPR109B show a more diffuse cellular localization and the receptors are nearly non-functional. (PMID:21655214)
• Activated HCAR3 signals to MAP kinase cascades via the PLC-dependent PKC and MMP-mediated EGFR pathways (PMID:22289163)
• HCA1/3 are necessary for breast cancer cells to balance lipid/fatty acid metabolism. (PMID:25839160)
• new insights into the G protein coupling profiles of the HCA receptors and the function of the receptor’s C terminus (PMID:26656756)
• Natural biased signaling of hydroxycarboxylic acid receptor 3 and G protein-coupled receptor 84. (PMID:32102673)
• Rare and potentially pathogenic variants in hydroxycarboxylic acid receptor genes identified in breast cancer cases. (PMID:34852802)
• Alterations in Kynurenine and NAD(+) Salvage Pathways during the Successful Treatment of Inflammatory Bowel Disease Suggest HCAR3 and NNMT as Potential Drug Targets. (PMID:34948292)
• Hydroxycarboxylic acid receptor 3 and GPR84 - Two metabolite-sensing G protein-coupled receptors with opposing functions in innate immune cells. (PMID:34968686)
• GPCR Screening Reveals that the Metabolite Receptor HCAR3 Regulates Epithelial Proliferation, Migration, and Cellular Respiration. (PMID:38103827)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hcar2	ENSMUSG00000045502
rattus_norvegicus	Hcar2	ENSRNOG00000071408

Paralogs (15): GPR31 (ENSG00000120436), GPR42 (ENSG00000126251), FFAR2 (ENSG00000126262), FFAR1 (ENSG00000126266), OXER1 (ENSG00000162881), OXGR1 (ENSG00000165621), P2RY1 (ENSG00000169860), P2RY6 (ENSG00000171631), GPR82 (ENSG00000171657), P2RY2 (ENSG00000175591), HCAR2 (ENSG00000182782), FFAR3 (ENSG00000185897), P2RY4 (ENSG00000186912), HCAR1 (ENSG00000196917), SUCNR1 (ENSG00000198829)

Protein

Protein identifiers

Hydroxycarboxylic acid receptor 3 — P49019 (reviewed: P49019)

Alternative names: G-protein coupled receptor 109B, G-protein coupled receptor HM74, G-protein coupled receptor HM74B, Niacin receptor 2, Nicotinic acid receptor 2

All UniProt accessions (1): P49019

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor for 3-hydroxyoctanoate, a fatty acid beta-oxidation intermediate. Signals through the inhibitory G(i)/o family of G-proteins. Acts as a negative feedback regulator of adipocyte lipolysis, helping to counterbalance prolipolytic signals during physiological or pathological elevations in beta-oxidation. Acts as a low affinity receptor for nicotinic acid. This pharmacological effect requires nicotinic acid doses that are much higher than those provided by a normal diet.

Subcellular location. Cell membrane.

Tissue specificity. Expression largely restricted to adipose tissue and spleen.

Miscellaneous. Exists only in humans and higher primates.

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

RefSeq proteins (1): NP_006009* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR051893	HCARs	Family

Pfam: PF00001

UniProt features (52 total): helix 10, topological domain 8, mutagenesis site 8, transmembrane region 7, sequence variant 6, turn 5, disulfide bond 3, binding site 2, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
8JEI	ELECTRON MICROSCOPY	2.73
9JID	ELECTRON MICROSCOPY	2.78
8JEF	ELECTRON MICROSCOPY	2.96
9KT6	ELECTRON MICROSCOPY	3.01
9JKT	ELECTRON MICROSCOPY	3.05
8IHJ	ELECTRON MICROSCOPY	3.07
9JKX	ELECTRON MICROSCOPY	3.18
8IHK	ELECTRON MICROSCOPY	3.21
9JKV	ELECTRON MICROSCOPY	3.26
9JKS	ELECTRON MICROSCOPY	3.31
9JIC	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49019-F1	79.66	0.52

Antibody-complex structures (SAbDab): 7 — 8IHJ, 8JEF, 8JEI, 9JIC, 9JID, 9JKT, 9JKX

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 (2): 179; 284

Disulfide bonds (3): 18–183, 19–266, 100–177

Mutagenesis-validated functional residues (8):

Position	Phenotype
86	reduces the agonistic activity of acifran.
86	increases the niacin binding affinity.
93	loss of acifran’s agonistic activity.
107	reduces the agonistic activity of acifran.
107	increases the niacin binding affinity.
111	loss of agonistic activity of acifran. suppresses the activation effect of oh-octanoid acid.
279	inhibits activation mediated by oh-octanoid acid.
284	loss of acifran’s agonistic activity. suppresses the activation effect of oh-octanoid acid.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-3296197	Hydroxycarboxylic acid-binding receptors
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 183 (showing top): MCLACHLAN_DENTAL_CARIES_UP, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, JAEGER_METASTASIS_DN, MODULE_45, MODULE_64, HALMOS_CEBPA_TARGETS_UP, FOXO4_01, FOXO1_01, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, WANG_ESOPHAGUS_CANCER_VS_NORMAL_DN, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, MODULE_289, GOBP_REGULATION_OF_CATABOLIC_PROCESS, HFH8_01

GO Biological Process (4): G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), negative regulation of lipid catabolic process (GO:0050995), signal transduction (GO:0007165)

GO Molecular Function (2): G protein-coupled receptor activity (GO:0004930), nicotinic acid receptor activity (GO:0070553)

GO Cellular Component (3): plasma membrane (GO:0005886), cell junction (GO:0030054), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor activity	2
cellular anatomical structure	2
signal transduction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
negative regulation of catabolic process	1
lipid catabolic process	1
negative regulation of lipid metabolic process	1
regulation of lipid catabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

612 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HCAR3	DENR	O43583	825
HCAR3	GPR148	Q8TDV2	595
HCAR3	GPR84	Q9NQS5	467
HCAR3	PNPO	Q9NVS9	406
HCAR3	HCAR2	Q8TDS4	394
HCAR3	ADH4	P08319	381
HCAR3	HSD3B2	P26439	372
HCAR3	GPRIN2	O60269	348
HCAR3	GPR150	Q8NGU9	320
HCAR3	CXCL10	P02778	307
HCAR3	GPR75	O95800	300
HCAR3	CXCL11	O14625	298
HCAR3	CXCL9	Q07325	284
HCAR3	CSF2RB	P32927	278
HCAR3	GPR132	Q9UNW8	271

IntAct

10 interactions, top by confidence:

A	B	Type	Score
RAMP1	HCAR3	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	HCAR3	psi-mi:“MI:0915”(physical association)	0.400
HCAR3	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
HCAR3	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	HCAR3	psi-mi:“MI:0915”(physical association)	0.400
HCAR3	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
purT	HCAR3	psi-mi:“MI:0915”(physical association)	0.000

ESM2 similar proteins: A0A4W3GG95, A7YY44, B0F9W3, B0UXR0, B2GV46, B3G515, B5X337, E7FEL0, O00398, O46685, O70526, P21556, P25023, P25105, P25116, P26824, P30411, P30558, P32299, P43657, P46002, P46093, P49019, P50132, P56488, Q00991, Q15743, Q1JQB3, Q28642, Q3UFD7, Q4G072, Q4KLH9, Q61038, Q62035, Q80Z39, Q8BFQ3, Q8BFU7, Q8BLG2, Q8BMC0, Q8BUD0

Diamond homologs: B2RPY5, B3DM66, O02664, O02836, O35210, O42384, O77408, O77590, O77621, P08908, P16395, P19327, P21917, P22270, P25095, P25104, P29754, P30555, P30556, P32250, P34969, P34976, P43240, P49019, P49146, P49220, P79113, P97295, Q0EAB6, Q0GBZ5, Q24563, Q25321, Q25322, Q25414, Q2YDN1, Q58CW4, Q5IS62, Q64264, Q6XXX9, Q6XXY0

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — AML.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	52
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2684685	GRCh37/hg19 12q24.31-24.33(chr12:121551496-133777902)x3	Pathogenic

SpliceAI

8 predictions. Top by Δscore:

Variant	Effect	Δscore
12:122714946:C:CC	acceptor_gain	0.3100
12:122714945:A:AC	acceptor_gain	0.3000
12:122715938:T:TA	donor_gain	0.2200
12:122715993:CCACG:C	acceptor_gain	0.2100
12:122715994:CACGC:C	acceptor_gain	0.2100
12:122715996:CG:C	acceptor_gain	0.2100
12:122715404:GCGTC:G	acceptor_gain	0.2000
12:122715938:TC:T	donor_gain	0.2000

AlphaMissense

2578 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:122716284:A:G	W152R	0.997
12:122716284:A:T	W152R	0.997
12:122716006:G:C	F244L	0.996
12:122716006:G:T	F244L	0.996
12:122716008:A:G	F244L	0.996
12:122716616:C:T	G41E	0.996
12:122716519:G:C	D73E	0.995
12:122716519:G:T	D73E	0.995
12:122716534:G:C	N68K	0.995
12:122716534:G:T	N68K	0.995
12:122715877:G:C	S287R	0.994
12:122715877:G:T	S287R	0.994
12:122715879:T:G	S287R	0.994
12:122716011:A:G	C243R	0.993
12:122716396:G:C	S114R	0.993
12:122716396:G:T	S114R	0.993
12:122716398:T:G	S114R	0.993
12:122716520:T:G	D73A	0.993
12:122716521:C:G	D73H	0.993
12:122716603:A:C	N45K	0.993
12:122716603:A:T	N45K	0.993
12:122716617:C:G	G41R	0.993
12:122716617:C:T	G41R	0.993
12:122715868:G:C	D290E	0.992
12:122715868:G:T	D290E	0.992
12:122716001:G:C	P246R	0.992
12:122716018:A:C	F240L	0.992
12:122716018:A:T	F240L	0.992
12:122716020:A:G	F240L	0.992
12:122716617:C:A	G41W	0.992

dbSNP variants (sampled 300 via entrez): RS1000961650 (12:122718338 G>A), RS1001079772 (12:122718591 C>T), RS1001842666 (12:122715089 A>C), RS1004526130 (12:122714945 A>G), RS1005024111 (12:122715278 C>T), RS1005150871 (12:122717588 A>G), RS1005245494 (12:122718052 A>C,G), RS1007025342 (12:122714445 T>G), RS1011385704 (12:122715331 G>A), RS1012065797 (12:122718144 C>A,T), RS1016823395 (12:122717205 T>G), RS1017784945 (12:122714481 A>G), RS1020398389 (12:122715365 G>A), RS1023509327 (12:122718309 A>T), RS1024663143 (12:122715057 A>G,T)

Disease associations

OMIM: gene MIM:606039 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST005412_5	Thrombin-activatable fibrinolysis inhibitor levels	7.000000e-07
GCST007491_2	Waist-to-hip ratio adjusted for BMI (recessive genetic model)	8.000000e-07
GCST007501_2	Waist-to-hip ratio adjusted for BMI (recessive genetic model)	9.000000e-07
GCST007503_2	Waist-to-hip ratio adjusted for BMI (recessive genetic model)	6.000000e-08
GCST90020024_248	A body shape index	5.000000e-14
GCST90020025_32	Waist-to-hip ratio adjusted for BMI	3.000000e-17
GCST90020027_1209	Waist-hip index	8.000000e-18
GCST90020029_472	Waist circumference adjusted for body mass index	7.000000e-21
GCST90020029_474	Waist circumference adjusted for body mass index	1.000000e-14

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4421 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 355,157 (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
CHEMBL573	NIACIN	4	351,963
CHEMBL2036958	SCH-900271	2	20
CHEMBL278488	ACIFRAN	2	3,174

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Hydroxycarboxylic acid receptors

Most potent curated ligand interactions (13 total), top 13:

Ligand	Action	Affinity	Parameter
compound 6o [PMID: 19524438]	Full agonist	8.52	pEC50
4-(n-propyl)amino-3-nitrobenzoic acid	Full agonist	7.52	pEC50
D-phenyllactic acid	Agonist	6.82	pEC50
5-methyl-5-(5-methylthiophen-3-yl)-4-oxo-4,5-dihydrofuran-2-carboxylic acid	Full agonist	6.7	pEC50
nicotinic acid	Full agonist	6.52	pEC50
IBC 293	Full agonist	6.4	pEC50
D-kynurenine	Full agonist	5.58	pEC50
2-hydroxyoctanoic acid	Full agonist	5.4	pEC50
compound 5b [PMID: 17358052]	Full agonist	5.3	pEC50
acifran	Full agonist	5.2	pEC50
3-hydroxyoctanoic acid	Full agonist	5.1	pEC50
D-phenylalanine	Full agonist	5.04	pEC50
D-tryptophan	Full agonist	5.01	pEC50

ChEMBL bioactivities

114 potent at pChembl≥5 of 129 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.50	EC50	3.162	nM	CHEMBL564300
7.84	EC50	14.45	nM	CHEMBL564914
7.53	EC50	29.51	nM	CHEMBL236011
7.38	EC50	41.69	nM	CHEMBL394468
7.29	EC50	51.29	nM	CHEMBL237733
7.28	EC50	52.48	nM	CHEMBL238375
7.24	EC50	57.54	nM	CHEMBL397616
7.23	EC50	59	nM	CHEMBL2036951
7.17	EC50	67	nM	CHEMBL2036954
7.15	EC50	70.79	nM	CHEMBL394468
7.14	EC50	72.44	nM	CHEMBL237524
7.02	EC50	96	nM	SCH-900271
7.00	EC50	100	nM	CHEMBL237945
7.00	EC50	100	nM	CHEMBL236013
6.92	EC50	120.2	nM	CHEMBL238376
6.85	EC50	140	nM	CHEMBL2036955
6.85	EC50	141.2	nM	CHEMBL559204
6.82	EC50	151.4	nM	CHEMBL237946
6.82	EC50	151.4	nM	CHEMBL391473
6.80	EC50	158.5	nM	CHEMBL236219
6.75	EC50	180	nM	CHEMBL424938
6.72	EC50	190	nM	CHEMBL2036813
6.70	EC50	199.5	nM	CHEMBL382096
6.70	EC50	199.5	nM	CHEMBL236028
6.64	EC50	229.1	nM	CHEMBL391547
6.59	EC50	257	nM	CHEMBL372727
6.59	EC50	257	nM	CHEMBL202351
6.59	EC50	257	nM	CHEMBL235144
6.59	EC50	257	nM	CHEMBL562675
6.57	EC50	270	nM	CHEMBL223566
6.57	EC50	269.1	nM	CHEMBL396879
6.55	EC50	281.8	nM	CHEMBL235141
6.54	EC50	288.4	nM	CHEMBL201048
6.52	EC50	302	nM	CHEMBL201409
6.52	EC50	300	nM	CHEMBL1671877
6.51	EC50	309	nM	CHEMBL394906
6.51	EC50	309	nM	CHEMBL392830
6.51	EC50	309	nM	CHEMBL238358
6.50	EC50	316	nM	ACIFRAN
6.50	EC50	316.2	nM	CHEMBL202157
6.49	EC50	323.6	nM	CHEMBL235615
6.48	EC50	331.1	nM	CHEMBL202206
6.44	EC50	363.1	nM	CHEMBL237077
6.43	EC50	370	nM	CHEMBL375493
6.42	EC50	380.2	nM	CHEMBL396878
6.41	EC50	389.1	nM	CHEMBL237735
6.40	EC50	398.1	nM	CHEMBL381638
6.40	EC50	398.1	nM	CHEMBL237732
6.23	EC50	588.8	nM	CHEMBL396073
6.22	EC50	602.6	nM	CHEMBL238386

PubChem BioAssay actives

128 with measured affinity, of 361 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
3-[bis(thiophen-3-ylmethyl)amino]-1H-pyrazole-5-carboxylic acid	428326: Agonist activity at GPR109b receptor transfected in CHOK1 cells assessed as inhibition of forskolin-induced cAMP generation by HTRF assay	ec50	0.0032	uM
3-[benzyl(thiophen-3-ylmethyl)amino]-1H-pyrazole-5-carboxylic acid	428326: Agonist activity at GPR109b receptor transfected in CHOK1 cells assessed as inhibition of forskolin-induced cAMP generation by HTRF assay	ec50	0.0144	uM
3-nitro-4-(propylamino)benzoic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.0295	uM
6-(prop-2-enylamino)pyridine-3-carboxylic acid	428326: Agonist activity at GPR109b receptor transfected in CHOK1 cells assessed as inhibition of forskolin-induced cAMP generation by HTRF assay	ec50	0.0417	uM
6-(propylamino)pyridine-3-carboxylic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.0513	uM
4-[methyl(propyl)amino]-3-nitrobenzoic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.0525	uM
3-nitro-4-(pentan-3-ylamino)benzoic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.0575	uM
5-(4,4-difluorobutyl)-1H-pyrano[2,3-d]pyrimidine-2,4,7-trione	663585: Agonist activity at human GPR109b	ec50	0.0590	uM
5-(2-cyclobutylethyl)-1H-pyrano[2,3-d]pyrimidine-2,4,7-trione	663585: Agonist activity at human GPR109b	ec50	0.0670	uM
6-(cyclobutylamino)pyridine-3-carboxylic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.0724	uM
5-[3-(1-methylcyclopropyl)propyl]-1H-pyrano[2,3-d]pyrimidine-2,4,7-trione	663585: Agonist activity at human GPR109b	ec50	0.0960	uM
3-nitro-4-(prop-2-enylamino)benzoic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.1000	uM
6-(butylamino)pyridine-3-carboxylic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.1000	uM
4-(dipropylamino)-3-nitrobenzoic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.1202	uM
5-(3-cyclopropylpropyl)-1H-pyrano[2,3-d]pyrimidine-2,4,7-trione	663585: Agonist activity at human GPR109b	ec50	0.1400	uM
3-[thiophen-2-ylmethyl(thiophen-3-ylmethyl)amino]-1H-pyrazole-5-carboxylic acid	428326: Agonist activity at GPR109b receptor transfected in CHOK1 cells assessed as inhibition of forskolin-induced cAMP generation by HTRF assay	ec50	0.1412	uM
4-(butan-2-ylamino)-3-nitrobenzoic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.1514	uM
6-(pentylamino)pyridine-3-carboxylic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.1514	uM
4-(butylamino)-3-nitrobenzoic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.1585	uM
5-methyl-5-(5-methylthiophen-3-yl)-4-oxofuran-2-carboxylic acid	281256: Activity at GPR109b in CHO cells assessed as inhibition of forskolin-induced cAMP generation	ec50	0.1800	uM
5-butyl-1H-pyrano[2,3-d]pyrimidine-2,4,7-trione	663585: Agonist activity at human GPR109b	ec50	0.1900	uM
1-(1-methoxypropan-2-yl)benzotriazole-5-carboxylic acid	260310: Agonistic activity at GPR109b by cAMP whole cell assay	ec50	0.1995	uM
4-(cyclobutylamino)-3-nitrobenzoic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.1995	uM
4-(ethylamino)-3-nitrobenzoic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.2291	uM
1-tert-butylbenzotriazole-5-carboxylic acid	260310: Agonistic activity at GPR109b by cAMP whole cell assay	ec50	0.2570	uM
1-(2-ethoxyethyl)benzotriazole-5-carboxylic acid	260310: Agonistic activity at GPR109b by cAMP whole cell assay	ec50	0.2570	uM
3-nitro-4-(propan-2-ylamino)benzoic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.2570	uM
3-[bis(thiophen-2-ylmethyl)amino]-1H-pyrazole-5-carboxylic acid	428326: Agonist activity at GPR109b receptor transfected in CHOK1 cells assessed as inhibition of forskolin-induced cAMP generation by HTRF assay	ec50	0.2570	uM
6-(pentan-3-ylamino)pyridine-3-carboxylic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.2692	uM
5-methyl-5-(5-methylthiophen-2-yl)-4-oxofuran-2-carboxylic acid	281256: Activity at GPR109b in CHO cells assessed as inhibition of forskolin-induced cAMP generation	ec50	0.2700	uM
3-nitro-4-(pentylamino)benzoic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.2818	uM
1-pentylbenzotriazole-5-carboxylic acid	260310: Agonistic activity at GPR109b by cAMP whole cell assay	ec50	0.2884	uM
5-(3-cyclopropylpropyl)-2-(difluoromethyl)-3H-pyrano[2,3-d]pyrimidine-4,7-dione	570173: Agonist activity at human GPR109b	ec50	0.3000	uM
1-(2-ethylsulfanylethyl)benzotriazole-5-carboxylic acid	260310: Agonistic activity at GPR109b by cAMP whole cell assay	ec50	0.3020	uM
4-(cyclopentylamino)-3-nitrobenzoic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.3090	uM
3-nitro-4-(oxolan-2-ylmethylamino)benzoic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.3090	uM
4-(cyclopropylamino)-3-nitrobenzoic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.3090	uM
5-methyl-4-oxo-5-phenylfuran-2-carboxylic acid	1232300: Agonist activity at HCA3 receptor (unknown origin) expressed in CHOK1 cells assessed as ERK1/2 phosphorylation by ELISA	ec50	0.3160	uM
1-(2-methoxyethyl)benzotriazole-5-carboxylic acid	260310: Agonistic activity at GPR109b by cAMP whole cell assay	ec50	0.3162	uM
6-(cyclopropylamino)pyridine-3-carboxylic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.3236	uM
1-butan-2-ylbenzotriazole-5-carboxylic acid	260310: Agonistic activity at GPR109b by cAMP whole cell assay	ec50	0.3311	uM
4-(3-methylbutan-2-ylamino)-3-nitrobenzoic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.3631	uM
5-(5-bromothiophen-3-yl)-5-methyl-4-oxofuran-2-carboxylic acid	281256: Activity at GPR109b in CHO cells assessed as inhibition of forskolin-induced cAMP generation	ec50	0.3700	uM
6-(butan-2-ylamino)pyridine-3-carboxylic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.3802	uM
6-(cyclopentylamino)pyridine-3-carboxylic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.3891	uM
6-(ethylamino)pyridine-3-carboxylic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.3981	uM
1-propan-2-ylbenzotriazole-5-carboxylic acid	260310: Agonistic activity at GPR109b by cAMP whole cell assay	ec50	0.3981	uM
4-(2-methoxyethylamino)-3-nitrobenzoic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.5888	uM
6-(propan-2-ylamino)pyridine-3-carboxylic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.6026	uM
6-(oxolan-2-ylmethylamino)pyridine-3-carboxylic acid	302806: Agonist activity at human GPR109b receptor transfected in CHOK1 cells assessed as reversal of forskolin-induced cAMP elevating effect by whole cell assay	ec50	0.6026	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, increases expression, decreases expression	4
Niacin	affects binding, increases phosphorylation, increases expression, increases activity, increases reaction	4
Benzo(a)pyrene	increases expression	3
Silicon Dioxide	increases expression	3
acifran	affects binding, increases activity, increases phosphorylation, increases reaction	2
Acetaminophen	increases expression, decreases expression	2
Carboxylic Acids	affects binding, increases activity	2
Oxygen	increases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
GSK-J4	increases expression	1
bisphenol F	decreases expression	1
urushiol	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
potassium perchlorate	decreases expression	1
terbufos	increases methylation	1
3,4-dichloroaniline	decreases expression	1
ciglitazone	affects binding, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
avobenzone	increases expression	1
1H-benzotriazole-5-carboxylic acid	affects binding, increases activity	1
di-n-butylphosphoric acid	affects expression	1
corosolic acid	increases expression	1
abrine	increases expression	1
Irinotecan	increases expression	1
Cyclic AMP	decreases abundance	1
Air Pollutants	decreases expression, increases abundance	1
Calcitriol	decreases expression	1
Calcium	increases abundance, affects reaction	1

ChEMBL screening assays

31 unique, capped per target: 24 functional, 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1002199	Functional	Agonist activity against GPR109b assessed as forskolin-induced cAMP accumulation relative to nicotinic acid	3-(1H-tetrazol-5-yl)-1,4,5,6-tetrahydro-cyclopentapyrazole (MK-0354): a partial agonist of the nicotinic acid receptor, G-protein coupled receptor 109a, with antilipolytic but no vasodilatory activity in mice. — J Med Chem
CHEMBL1105989	Binding	Binding affinity to GPR109B	Discovery of a biaryl cyclohexene carboxylic acid (MK-6892): a potent and selective high affinity niacin receptor full agonist with reduced flushing profiles in animals as a preclinical candidate. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KV28	cAMP Hunter CHO-K1 GPR109B Gi	Spontaneously immortalized cell line	Female
CVCL_KX23	PathHunter CHO-K1 GPR109B beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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