FFAR3

Summary

FFAR3 (free fatty acid receptor 3, HGNC:4499) is a protein-coding gene on chromosome 19q13.12, encoding Free fatty acid receptor 3 (O14843). G protein-coupled receptor that is activated by a major product of dietary fiber digestion, the short chain fatty acids (SCFAs), and that plays a role in the regulation of whole-body energy homeostasis and in intestinal immunity.

Enables G protein-coupled receptor activity. Involved in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway and cellular response to fatty acid. Located in plasma membrane.

Source: NCBI Gene 2865 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 86 total
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005304

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4499
Approved symbol	FFAR3
Name	free fatty acid receptor 3
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	FFA3R
Ensembl gene	ENSG00000185897
Ensembl biotype	protein_coding
OMIM	603821
Entrez	2865

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000327809, ENST00000594310, ENST00000965195

RefSeq mRNA: 1 — MANE Select: NM_005304 NM_005304

CCDS: CCDS12459

Canonical transcript exons

ENST00000327809 — 2 exons

Exon	Start	End
ENSE00001296125	35358460	35358649
ENSE00001298206	35358880	35360489

Expression profiles

Bgee: expression breadth ubiquitous, 108 present calls, max score 84.45.

Top tissues by expression

126 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	84.45	silver quality
blood	UBERON:0000178	73.79	gold quality
omental fat pad	UBERON:0010414	69.57	gold quality
islet of Langerhans	UBERON:0000006	65.30	gold quality
adipose tissue	UBERON:0001013	65.14	gold quality
granulocyte	CL:0000094	63.63	gold quality
vermiform appendix	UBERON:0001154	62.63	gold quality
apex of heart	UBERON:0002098	61.79	gold quality
subcutaneous adipose tissue	UBERON:0002190	61.38	gold quality
monocyte	CL:0000576	59.61	gold quality
leukocyte	CL:0000738	59.51	gold quality
muscle layer of sigmoid colon	UBERON:0035805	57.83	gold quality
thoracic mammary gland	UBERON:0005200	55.72	gold quality
gall bladder	UBERON:0002110	54.50	gold quality
smooth muscle tissue	UBERON:0001135	53.43	gold quality
spleen	UBERON:0002106	52.84	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	52.51	gold quality
fundus of stomach	UBERON:0001160	52.48	gold quality
duodenum	UBERON:0002114	52.11	gold quality
pancreas	UBERON:0001264	51.40	gold quality
bone marrow	UBERON:0002371	50.85	gold quality
lymph node	UBERON:0000029	50.80	gold quality
colon	UBERON:0001155	50.00	gold quality
hindlimb stylopod muscle	UBERON:0004252	49.24	silver quality
intestine	UBERON:0000160	48.65	gold quality
placenta	UBERON:0001987	48.31	gold quality
right lobe of thyroid gland	UBERON:0001119	48.26	gold quality
body of stomach	UBERON:0001161	48.04	gold quality
urinary bladder	UBERON:0001255	47.26	gold quality
stomach	UBERON:0000945	47.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting FFAR3, 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-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-2115-5P	98.66	68.07	1191
HSA-MIR-6865-3P	97.54	64.67	684
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-215-3P	97.02	68.01	1209
HSA-MIR-616-3P	96.82	66.99	784
HSA-MIR-4471	95.11	66.84	755
HSA-MIR-8059	95.11	66.30	646

Literature-anchored findings (GeneRIF, showing 23)

• characterization of GP41 in human tissue as a receptor for short chain fatty acids (PMID:12711604)
• C2-C6 short-chain fatty acids, ligands of an orphan G protein-coupled receptor GPR41, stimulate leptin expression in both a mouse adipocyte cell line and mouse adipose tissue in primary culture (PMID:14722361)
• GPR41 and 43 mediate SCFA signaling in mammary epithelial cells and thereby play an important role in their stress management. (PMID:16887331)
• analysis of conserved polar residues in transmembrane domains V, VI, and VII of free fatty acid receptor 2 and free fatty acid receptor 3 are required for the binding and function of short chain fatty acids (PMID:18801738)
• Results suggest that GPR41 expressed in human colonic mucosa may function as a sensor for luminal short-chain fatty acids. (PMID:19574715)
• Study presents evidence showing that the six amino acid differences, including that R/W174 are polymorphisms rather than gene-specific differences between GPR41 and GPR42. (PMID:19630535)
• Selective orthosteric free fatty acid receptor 2 (FFA2) agonists: identification of the structural and chemical requirements for selective activation of FFA2 versus FFA3. (PMID:21220428)
• GPR41 gene expression is mediated by internal ribosome entry site (IRES)-dependent translation of bicistronic mRNA encoding GPR40 and GPR41 proteins (PMID:22493486)
• Propionate-stimulated GPR41 strongly coupled to ERK1/2 activation, while the coupling of linoleic acid-activated GPR40 and acetate-activated GPR43 was weaker. (PMID:22712802)
• GPR41 activation inhibits histone acetylation and cell growth. (PMID:22884094)
• Extracellular ionic locks determine variation in constitutive activity and ligand potency between species orthologs of the free fatty acid receptors FFA2 and FFA3 (PMID:23066016)
• a significant correlation between a higher body mass index and lower methylation in the promoter region of FFAR3 in type 2 diabetes and obesity patients (PMID:24325907)
• FFAR3 is expressed in pancreatic beta cells and mediates an inhibition of insulin secretion by coupling to Gi-type G proteins. (PMID:25581519)
• Our data suggest that GPR42 be reclassified as a functioning gene and that recognition of sequence and copy number polymorphism of the FFAR3/GPR42 complex be considered during genetic and pharmacological investigation of these receptors. (PMID:26260360)
• a single dose of soluble fibre was able to significantly reduce airway inflammation in stable asthma by downregulating GPR43 and GPR41 (PMID:28075383)
• Short-chain fatty acids lowered TNF-alpha-induced MCP-1 expression by reducing phosphorylation of p38 MAPK and JNK in a GPR41/GRP43-dependent manner in renal cortical epithelial cells. (PMID:28322790)
• Data suggest that cytokines TNFalpha and interleukin-1b markedly reduce GPR120/FFAR4 expression in adipocytes; in contrast, these cytokines induce expression of GPR84 and GPR41/FFAR3 in adipocytes. These studies were conducted in adipocytes cultured from subcutaneous adipose tissue. (GPR = G-protein coupled receptor; FFAR = free fatty acid receptor) (PMID:28835131)
• FFAR2 and FFAR3 interact to form a heteromer in primary monocytes and macrophages via proximity ligation assay, and during heterologous expression in HEK293 cells via bimolecular fluorescence complementation and fluorescence resonance energy transfer. FFAR2 and FFAR3 may interact to form a receptor heteromer with signaling that is distinct from the parent homomers. (PMID:28883043)
• Metabolic and physiological role of FFAR1 (GPR40), FFAR4 (GPR120), FFAR3 (GPR41) and FFAR2 (GPR43) is REVIEWED. (PMID:31487233)
• The short-chain free fatty acid receptor FFAR3 is expressed and potentiates contraction in human airway smooth muscle. (PMID:32209026)
• FFA2-, but not FFA3-agonists inhibit GSIS of human pseudoislets: a comparative study with mouse islets and rat INS-1E cells. (PMID:33020504)
• Genetic Inactivation of Free Fatty Acid Receptor 3 Impedes Behavioral Deficits and Pathological Hallmarks in the APPswe Alzheimer’s Disease Mouse Model. (PMID:35408893)
• Regulator of G-Protein Signaling-4 Attenuates Cardiac Adverse Remodeling and Neuronal Norepinephrine Release-Promoting Free Fatty Acid Receptor FFAR3 Signaling. (PMID:35628613)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-211g8.7	ENSDARG00000058535
danio_rerio	si:dkey-211g8.6	ENSDARG00000063088
danio_rerio		ENSDARG00000079661
danio_rerio	si:ch73-90p23.1	ENSDARG00000097901
mus_musculus	Ffar3	ENSMUSG00000019429
rattus_norvegicus	Ffar3	ENSRNOG00000037467

Paralogs (15): GPR31 (ENSG00000120436), GPR42 (ENSG00000126251), FFAR2 (ENSG00000126262), FFAR1 (ENSG00000126266), OXER1 (ENSG00000162881), OXGR1 (ENSG00000165621), P2RY1 (ENSG00000169860), P2RY6 (ENSG00000171631), GPR82 (ENSG00000171657), P2RY2 (ENSG00000175591), HCAR2 (ENSG00000182782), P2RY4 (ENSG00000186912), HCAR1 (ENSG00000196917), SUCNR1 (ENSG00000198829), HCAR3 (ENSG00000255398)

Protein

Protein identifiers

Free fatty acid receptor 3 — O14843 (reviewed: O14843)

Alternative names: G-protein coupled receptor 41

All UniProt accessions (2): A0A0K0PUW7, O14843

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor that is activated by a major product of dietary fiber digestion, the short chain fatty acids (SCFAs), and that plays a role in the regulation of whole-body energy homeostasis and in intestinal immunity. In omnivorous mammals, the short chain fatty acids acetate, propionate and butyrate are produced primarily by the gut microbiome that metabolizes dietary fibers. SCFAs serve as a source of energy but also act as signaling molecules. That G protein-coupled receptor is probably coupled to the pertussis toxin-sensitive, G(i/o)-alpha family of G proteins. Its activation results in the formation of inositol 1,4,5-trisphosphate, the mobilization of intracellular calcium, the phosphorylation of the MAPK3/ERK1 and MAPK1/ERK2 kinases and the inhibition of intracellular cAMP accumulation. Activated by SCFAs and by beta-hydroxybutyrate, a ketone body produced by the liver upon starvation, it inhibits N-type calcium channels and modulates the activity of sympathetic neurons through a signaling cascade involving the beta and gamma subunits of its coupled G protein, phospholipase C and MAP kinases. Thereby, it may regulate energy expenditure through the control of the sympathetic nervous system that controls for instance heart rate. Upon activation by SCFAs accumulating in the intestine, it may also signal to the brain via neural circuits which in turn would regulate intestinal gluconeogenesis. May also control the production of hormones involved in whole-body energy homeostasis. May for instance, regulate blood pressure through renin secretion. May also regulate secretion of the PYY peptide by enteroendocrine cells and control gut motility, intestinal transit rate, and the harvesting of energy from SCFAs produced by gut microbiota. May also indirectly regulate the production of LEP/Leptin, a hormone acting on the CNS to inhibit food intake, in response to the presence of short-chain fatty acids in the intestine. Finally, may also play a role in glucose homeostasis. Besides its role in energy homeostasis, may play a role in intestinal immunity. May mediate the activation of the inflammatory and immune response by SCFAs in the gut, regulating the rapid production of chemokines and cytokines by intestinal epithelial cells. Among SCFAs, the fatty acids containing less than 6 carbons, the most potent activators are probably propionate, butyrate and pentanoate while acetate is a poor activator.

Subcellular location. Cell membrane.

Tissue specificity. Highest level in adipose tissue, and lower expression across all tissues tested. Expressed in sympathetic ganglia.

Polymorphism. The 6 amino acid differences at positions 44, 45, 174, 227, 256 and 346 between GPR42 and FFAR3, are polymorphic in the human population. The frequency of the probable inactive allele of FFAR3, with a Trp at position 174 was estimated to 1%.

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

RefSeq proteins (1): NP_005295* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR013312	GPR40-rel_orph	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (43 total): helix 9, topological domain 8, transmembrane region 7, sequence variant 6, mutagenesis site 5, turn 2, chain 1, region of interest 1, compositionally biased region 1, glycosylation site 1, disulfide bond 1, strand 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8J20	ELECTRON MICROSCOPY	3.2
8J21	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14843-F1	86.90	0.66

Antibody-complex structures (SAbDab): 2 — 8J20, 8J21

Functional residue map

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

Disulfide bonds (1): 88–169

Glycosylation sites (1): 166

Mutagenesis-validated functional residues (5):

Position	Phenotype
146	partial loss of scfa-induced g protein-coupled receptor activity.
158	gain of scfa-independent constitutive g protein-coupled receptor activity.
185	loss of scfa-induced g protein-coupled receptor activity.
245	loss of scfa-induced g protein-coupled receptor activity.
258	loss of scfa-induced g protein-coupled receptor activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-416476	G alpha (q) signalling events
R-HSA-444209	Free fatty acid receptors

MSigDB gene sets: 123 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_POSITIVE_REGULATION_OF_ACUTE_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GOBP_ORGAN_OR_TISSUE_SPECIFIC_IMMUNE_RESPONSE, GOBP_CELL_CELL_SIGNALING, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT

GO Biological Process (15): mucosal immune response (GO:0002385), positive regulation of cytokine production involved in immune response (GO:0002720), positive regulation of acute inflammatory response to non-antigenic stimulus (GO:0002879), inflammatory response (GO:0006954), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), regulation of norepinephrine secretion (GO:0014061), positive regulation of chemokine production (GO:0032722), negative regulation of blood pressure (GO:0045776), regulation of insulin receptor signaling pathway (GO:0046626), regulation of hormone biosynthetic process (GO:0046885), cellular response to fatty acid (GO:0071398), regulation of peptide hormone secretion (GO:0090276), immune system process (GO:0002376), signal transduction (GO:0007165)

GO Molecular Function (3): G protein-coupled receptor activity (GO:0004930), lipid binding (GO:0008289), protein binding (GO:0005515)

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

Reactome top-level categories

Rollup of top-2 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of cytokine production	2
binding	2
organ or tissue specific immune response	1
cytokine production involved in immune response	1
positive regulation of production of molecular mediator of immune response	1
regulation of cytokine production involved in immune response	1
acute inflammatory response to non-antigenic stimulus	1
positive regulation of acute inflammatory response	1
regulation of acute inflammatory response to non-antigenic stimulus	1
defense response	1
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
norepinephrine secretion	1
regulation of catecholamine secretion	1
chemokine production	1
regulation of chemokine production	1
regulation of blood pressure	1
insulin receptor signaling pathway	1
regulation of signal transduction	1
regulation of biosynthetic process	1
regulation of hormone metabolic process	1
hormone biosynthetic process	1
response to fatty acid	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
regulation of peptide secretion	1
peptide hormone secretion	1
regulation of hormone secretion	1
biological_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

1010 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FFAR3	FFAR4	Q5NUL3	860
FFAR3	CD22	P20273	839
FFAR3	GAL	P22466	837
FFAR3	GCG	P01275	834
FFAR3	PYY	P10082	828
FFAR3	GPR84	Q9NQS5	814
FFAR3	ALDH18A1	P54886	760
FFAR3	GPR119	Q8TDV5	690
FFAR3	GPBAR1	Q8TDU6	672
FFAR3	SLC5A8	Q8N695	645
FFAR3	FFAR2	O15552	620
FFAR3	HCAR2	Q8TDS4	595
FFAR3	GNAQ	P50148	589
FFAR3	GLP1R	P43220	586
FFAR3	GNAT3	A8MTJ3	585

IntAct

43 interactions, top by confidence:

A	B	Type	Score
FFAR3	TEX264	psi-mi:“MI:0915”(physical association)	0.560
FFAR3	YIPF1	psi-mi:“MI:0915”(physical association)	0.560
FFAR3	UNC93B1	psi-mi:“MI:0915”(physical association)	0.560
FFAR3	SLC41A1	psi-mi:“MI:0915”(physical association)	0.560
FFAR3	CTXN3	psi-mi:“MI:0915”(physical association)	0.560
FFAR3	COMT	psi-mi:“MI:0915”(physical association)	0.560
FFAR3	TREX1	psi-mi:“MI:0915”(physical association)	0.560
FFAR3	LAT	psi-mi:“MI:0915”(physical association)	0.560
FFAR3	SERINC1	psi-mi:“MI:0915”(physical association)	0.560
FFAR3	LTC4S	psi-mi:“MI:0915”(physical association)	0.560
FFAR3	CD79A	psi-mi:“MI:0915”(physical association)	0.560
FFAR3	EFNA5	psi-mi:“MI:0915”(physical association)	0.560
FFAR3	TOMM6	psi-mi:“MI:0915”(physical association)	0.560
FFAR3	KCNIP3	psi-mi:“MI:0915”(physical association)	0.560
UNC93B1	FFAR3	psi-mi:“MI:0915”(physical association)	0.000
SLC41A1	FFAR3	psi-mi:“MI:0915”(physical association)	0.000
CTXN3	FFAR3	psi-mi:“MI:0915”(physical association)	0.000
COMT	FFAR3	psi-mi:“MI:0915”(physical association)	0.000
TREX1	FFAR3	psi-mi:“MI:0915”(physical association)	0.000
LAT	FFAR3	psi-mi:“MI:0915”(physical association)	0.000
TEX264	FFAR3	psi-mi:“MI:0915”(physical association)	0.000
YIPF1	FFAR3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): FFAR3 (Synthetic Lethality), FFAR3 (Two-hybrid), FFAR3 (Two-hybrid), FFAR3 (Two-hybrid), FFAR3 (Two-hybrid), FFAR3 (Two-hybrid), FFAR3 (Two-hybrid), FFAR3 (Two-hybrid), FFAR3 (Two-hybrid), CTXN3 (Two-hybrid), LTC4S (Two-hybrid), LAT (Two-hybrid), TREX1 (Two-hybrid), TOMM6 (Two-hybrid)

ESM2 similar proteins: A0A6I8PUB9, O00155, O00270, O14842, O14843, O15529, O43603, O46685, O60755, O88626, O88634, O88853, O88854, O88855, P0C5I1, P46092, P46093, P50132, Q149R9, Q15722, Q15743, Q1JQB3, Q3T181, Q3UFD7, Q3ZC80, Q4KLH9, Q6XKD3, Q76JU8, Q76JU9, Q76JV1, Q86VZ1, Q8BUD0, Q8BYC4, Q8HYC3, Q8K3T4, Q8TDS5, Q8TDU9, Q920E0, Q924U0, Q96G91

Diamond homologs: A0A4W3GG95, A0A6I8PUB9, B2GV46, B5X337, D4A7K7, E7FEL0, E9QJ73, F8VQN3, O00270, O08726, O08858, O14842, O14843, O15529, O42179, O43603, O46685, O60755, O77408, O88410, O88626, O88634, O88853, P21109, P23944, P25024, P25025, P35344, P35383, P35414, P41231, P41232, P46092, P46093, P49652, P49682, P49683, P50132, P51675, P51679

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
FFAR3	“up-regulates activity”	GNAI1	binding
FFAR3	“up-regulates activity”	GNAI3	binding
FFAR3	“up-regulates activity”	GNA12	binding
“propionic acid”	“up-regulates activity”	FFAR3	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	73
Likely benign	10
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

115 predictions. Top by Δscore:

Variant	Effect	Δscore
19:35358878:A:AG	acceptor_gain	1.0000
19:35358878:AGT:A	acceptor_gain	1.0000
19:35358878:AGTG:A	acceptor_gain	1.0000
19:35358879:G:GA	acceptor_gain	1.0000
19:35358879:GT:G	acceptor_gain	1.0000
19:35358879:GTG:G	acceptor_gain	1.0000
19:35358879:GTGG:G	acceptor_gain	1.0000
19:35358876:C:G	acceptor_gain	0.9900
19:35358876:CCAGT:C	acceptor_loss	0.9900
19:35358877:CAGT:C	acceptor_loss	0.9900
19:35358878:A:G	acceptor_loss	0.9900
19:35358879:GTGGC:G	acceptor_gain	0.9900
19:35358875:A:AG	acceptor_gain	0.9700
19:35358526:G:GG	donor_gain	0.9600
19:35358647:CAG:C	donor_loss	0.9600
19:35358648:AGGTG:A	donor_loss	0.9600
19:35358650:G:GA	donor_loss	0.9600
19:35358651:T:A	donor_loss	0.9600
19:35358880:T:TA	acceptor_gain	0.9500
19:35358646:GCAG:G	donor_gain	0.9400
19:35358878:AGTGG:A	acceptor_gain	0.9400
19:35358967:T:TA	acceptor_gain	0.9300
19:35358877:CAGTG:C	acceptor_gain	0.9100
19:35358881:G:A	acceptor_gain	0.9000
19:35358876:CCAG:C	acceptor_gain	0.8600
19:35358636:TCTCA:T	donor_gain	0.8500
19:35358875:ACCAG:A	acceptor_gain	0.8400
19:35358879:G:T	acceptor_gain	0.8400
19:35358874:CACCA:C	acceptor_gain	0.8200
19:35358650:G:GG	donor_gain	0.7800

AlphaMissense

2232 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:35359218:A:C	S110R	0.986
19:35359220:C:A	S110R	0.986
19:35359220:C:G	S110R	0.986
19:35359296:A:C	S136R	0.986
19:35359298:T:A	S136R	0.986
19:35359298:T:G	S136R	0.986
19:35359332:A:C	S148R	0.977
19:35359334:C:A	S148R	0.977
19:35359334:C:G	S148R	0.977
19:35359683:A:C	S265R	0.965
19:35359685:C:A	S265R	0.965
19:35359685:C:G	S265R	0.965
19:35359058:C:A	N56K	0.964
19:35359058:C:G	N56K	0.964
19:35359308:T:A	W140R	0.961
19:35359308:T:C	W140R	0.961
19:35359407:T:C	F173L	0.961
19:35359409:C:A	F173L	0.961
19:35359409:C:G	F173L	0.961
19:35359133:G:C	W81C	0.960
19:35359133:G:T	W81C	0.960
19:35359659:T:A	W257R	0.959
19:35359659:T:C	W257R	0.959
19:35359467:T:C	F193L	0.952
19:35359469:T:A	F193L	0.952
19:35359469:T:G	F193L	0.952
19:35359599:T:C	C237R	0.951
19:35359602:T:C	F238L	0.950
19:35359604:T:A	F238L	0.950
19:35359604:T:G	F238L	0.950

dbSNP variants (sampled 300 via entrez): RS1000331574 (19:35357481 G>A,T), RS1000390325 (19:35358130 A>G,T), RS1000783467 (19:35360130 T>C), RS1000845896 (19:35357892 A>G), RS1001121906 (19:35356367 T>G), RS1001130759 (19:35360877 A>T), RS1002911817 (19:35356629 C>T), RS1003250433 (19:35357789 A>C), RS1003670844 (19:35357593 C>T), RS1006871121 (19:35357158 A>G), RS1009285421 (19:35358096 T>A), RS1009337642 (19:35357819 G>A), RS1011682715 (19:35356675 G>A), RS1013600827 (19:35356426 T>C), RS1013693039 (19:35360020 G>A)

Disease associations

OMIM: gene MIM:603821 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5201 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 4,803,028 (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
CHEMBL539	ACETIC ACID	4	3,621,057
CHEMBL14021	PROPIONIC ACID	2	732,527
CHEMBL14227	BUTYRIC ACID	2	424,980
CHEMBL62381	SODIUM BUTYRATE	2	24,464

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Free fatty acid receptors

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

Ligand	Action	Affinity	Parameter
(S)-4-CMTB	Agonist	6.4	pKi
propanoic acid	Full agonist	5.7	pEC50
FHQC	Agonist	5.65	pEC50
pentanoic acid	Full agonist	5.4	pEC50
butyric acid	Full agonist	4.9	pEC50
isobutyric acid	Full agonist	4.8	pEC50
acetic acid	Full agonist	3.9	pEC50
1-methylcyclopropanecarboxylic acid	Full agonist	3.9	pEC50

ChEMBL bioactivities

85 potent at pChembl≥5 of 103 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.89	EC50	128.8	nM	CHEMBL4564389
6.84	EC50	144.5	nM	CHEMBL4436229
6.79	EC50	162.2	nM	CHEMBL4530642
6.72	EC50	190.6	nM	CHEMBL4567723
6.66	EC50	220	nM	CHEMBL5270112
6.66	EC50	220	nM	CHEMBL5275861
6.66	EC50	220	nM	CHEMBL5284951
6.66	EC50	220	nM	CHEMBL5281556
6.66	EC50	220	nM	CHEMBL1672755
6.66	EC50	220	nM	CHEMBL5277000
6.66	EC50	220	nM	CHEMBL2036813
6.61	EC50	245.5	nM	CHEMBL4547569
6.60	EC50	251.2	nM	CHEMBL4581781
6.60	EC50	251.2	nM	CHEMBL4442868
6.58	EC50	263	nM	CHEMBL4584743
6.54	EC50	288.4	nM	CHEMBL4513816
6.45	EC50	354.8	nM	CHEMBL4473184
6.43	EC50	371.5	nM	CHEMBL4567192
6.42	EC50	380.2	nM	CHEMBL4560915
6.40	EC50	398.1	nM	CHEMBL4516265
6.35	EC50	447	nM	CHEMBL5574528
6.30	EC50	501.2	nM	CHEMBL4447610
6.28	EC50	524.8	nM	CHEMBL4448591
6.28	EC50	524.8	nM	CHEMBL4470184
6.27	EC50	537	nM	CHEMBL4569482
6.27	EC50	537	nM	CHEMBL4448591
6.23	EC50	588.8	nM	CHEMBL4567938
6.22	EC50	602.6	nM	CHEMBL4547759
6.21	EC50	616.6	nM	CHEMBL4470725
6.19	EC50	645.6	nM	CHEMBL4440835
6.17	EC50	679	nM	CHEMBL5594815
6.16	EC50	691.8	nM	CHEMBL4545039
6.16	EC50	691.8	nM	CHEMBL4515057
6.16	EC50	691.8	nM	CHEMBL4457531
6.15	EC50	708	nM	CHEMBL4452922
6.14	EC50	724.4	nM	CHEMBL4443269
6.13	EC50	741	nM	CHEMBL4564389
6.06	EC50	871	nM	CHEMBL4592426
6.00	EC50	1000	nM	CHEMBL4439667
5.97	EC50	1072	nM	CHEMBL4450056
5.96	EC50	1096	nM	CHEMBL4449702
5.96	EC50	1096	nM	CHEMBL4476587
5.92	EC50	1202	nM	CHEMBL4457531
5.92	EC50	1202	nM	CHEMBL4570341
5.91	EC50	1230	nM	CHEMBL4578663
5.87	EC50	1349	nM	CHEMBL4574477
5.86	EC50	1380	nM	CHEMBL4584743
5.86	EC50	1380	nM	CHEMBL4471380
5.80	EC50	1585	nM	CHEMBL4470372
5.79	EC50	1622	nM	CHEMBL4570341

PubChem BioAssay actives

84 with measured affinity, of 371 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-(2,5-dichlorophenyl)-4-(furan-2-yl)-2-methyl-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.1288	uM
N-(2,5-dichlorophenyl)-2-methyl-5-oxo-4-propyl-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.1445	uM
4-cyclopentyl-N-(2,5-dichlorophenyl)-2-methyl-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.1622	uM
N-(2,5-dichlorophenyl)-2-methyl-4-(1,3-oxazol-2-yl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.1905	uM
5-butyl-1H-pyrano[2,3-d]pyrimidine-2,4,7-trione	1939798: Agonist activity at FFA3 (unknown origin) expressed in human Flp-In-293 cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by Lance cAMP assay	ec50	0.2200	uM
5-butyl-2-sulfanylidene-1H-pyrano[2,3-d]pyrimidine-4,7-dione	1939798: Agonist activity at FFA3 (unknown origin) expressed in human Flp-In-293 cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by Lance cAMP assay	ec50	0.2200	uM
5-(4-chlorobutyl)-1H-pyrano[2,3-d]pyrimidine-2,4,7-trione	1939798: Agonist activity at FFA3 (unknown origin) expressed in human Flp-In-293 cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by Lance cAMP assay	ec50	0.2200	uM
5-(4-chlorobutyl)-2-sulfanylidene-1H-pyrano[2,3-d]pyrimidine-4,7-dione	1939798: Agonist activity at FFA3 (unknown origin) expressed in human Flp-In-293 cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by Lance cAMP assay	ec50	0.2200	uM
5-propyl-2-sulfanylidene-1H-pyrano[2,3-d]pyrimidine-4,7-dione	1939798: Agonist activity at FFA3 (unknown origin) expressed in human Flp-In-293 cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by Lance cAMP assay	ec50	0.2200	uM
5-ethyl-2-sulfanylidene-1H-pyrano[2,3-d]pyrimidine-4,7-dione	1939798: Agonist activity at FFA3 (unknown origin) expressed in human Flp-In-293 cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by Lance cAMP assay	ec50	0.2200	uM
5-methyl-2-sulfanylidene-1H-pyrano[2,3-d]pyrimidine-4,7-dione	1939798: Agonist activity at FFA3 (unknown origin) expressed in human Flp-In-293 cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by Lance cAMP assay	ec50	0.2200	uM
4-(5-bromofuran-2-yl)-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.2455	uM
4-cyclopropyl-N-(2,5-dichlorophenyl)-2-methyl-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.2512	uM
N-(2,5-dichlorophenyl)-2-methyl-5-oxo-4-(1,3-thiazol-2-yl)-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.2512	uM
4-butyl-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	0.2630	uM
4-cyclopentyl-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.2884	uM
4-ethyl-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	0.3548	uM
4-(furan-2-yl)-N-(2-methoxyphenyl)-2-methyl-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.3715	uM
5-cyano-2,6-dimethyl-N-(2-methylphenyl)-4-(2-methylpropyl)-1,4-dihydropyridine-3-carboxamide	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	0.3802	uM
2-methyl-N-(2-methylphenyl)-5-oxo-4-pentyl-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	0.3981	uM
N-(2,5-dichlorophenyl)-2-methyl-5-oxo-4-[5-(2,3,4-trifluorophenyl)furan-2-yl]-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	2107868: Agonist activity at doxycyclin-induced GPR41 (unknown origin) overexpressed in HEK293 cells assessed as decrease in forskolin-induced cAMP level	ec50	0.4470	uM
4-butan-2-yl-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	0.5012	uM
4-(furan-2-yl)-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.5248	uM
2-methyl-N-(2-methylphenyl)-4-(2-methylpropyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	0.5248	uM
4-(furan-3-yl)-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.5370	uM
2-methyl-N-(2-methylphenyl)-5-oxo-4-(2-phenylethyl)-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	0.5888	uM
4-cyclopropyl-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.6026	uM
methyl 2-methyl-4-(2-methylpropyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxylate	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	0.6166	uM
N-(2-chloro-5-methylphenyl)-2-methyl-5-oxo-4-propyl-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.6456	uM
4-[5-(3,5-difluorophenyl)furan-2-yl]-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	2107868: Agonist activity at doxycyclin-induced GPR41 (unknown origin) overexpressed in HEK293 cells assessed as decrease in forskolin-induced cAMP level	ec50	0.6790	uM
2-methyl-N-(2-methylphenyl)-5-oxo-4-propyl-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	0.6918	uM
methyl 2,6-dimethyl-5-[(2-methylphenyl)carbamoyl]-4-(2-methylpropyl)-1,4-dihydropyridine-3-carboxylate	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	0.6918	uM
4-(furan-2-yl)-2-methyl-N-(4-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.6918	uM
N-(2-chlorophenyl)-2-methyl-4-(2-methylpropyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.7079	uM
2-methyl-N-(2-methylphenyl)-5-oxo-4-[(E)-2-phenylethenyl]-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	0.7244	uM
N-(2-chlorophenyl)-2-methyl-5-oxo-4-propyl-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.8710	uM
4-(1-benzofuran-2-yl)-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.0000	uM
N-(3-chlorophenyl)-2-methyl-5-oxo-4-propyl-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.0715	uM
N-(2-chloro-5-methoxyphenyl)-2-methyl-5-oxo-4-propyl-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.0965	uM
2-methyl-4-(5-methylfuran-2-yl)-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.0965	uM
2-methyl-N-(2-methylphenyl)-5-oxo-4-thiophen-2-yl-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	1.2023	uM
2-methyl-N-(2-methylphenyl)-5-oxo-4-phenyl-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.2303	uM
4-(3-bromophenyl)-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.3490	uM
2-methyl-N-(2-methylphenyl)-4-(4-methylthiophen-2-yl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.3804	uM
4-(furan-2-yl)-2-methyl-N-(3-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.5849	uM
4-(4-bromophenyl)-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.6218	uM
N-(2,5-dichlorophenyl)-2-methyl-4-(1,3-oxazol-4-yl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.6596	uM
N-(2,5-dichlorophenyl)-2-methyl-5-oxo-4-(1,3-thiazol-5-yl)-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.7783	uM
N-(2,5-dichlorophenyl)-2-methyl-5-oxo-4-(1,3-thiazol-4-yl)-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.9498	uM
2-methyl-N-(2-methylphenyl)-5-oxo-4-[3-(trifluoromethyl)phenyl]-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	2.8184	uM

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	2
2-palmitoylglycerol	increases expression	1
gardiquimod	increases expression, decreases reaction	1
Resveratrol	decreases expression, affects cotreatment	1
Amiodarone	increases expression	1
Benzo(a)pyrene	affects methylation	1
Hydralazine	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tretinoin	increases expression	1
Protein Kinase Inhibitors	decreases reaction, increases expression	1

ChEMBL screening assays

56 unique, capped per target: 43 functional, 13 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1069234	Functional	Agonist activity at FFA3 receptor up to 30 uM	The first synthetic agonists of FFA2: Discovery and SAR of phenylacetamides as allosteric modulators. — Bioorg Med Chem Lett
CHEMBL2320490	Binding	Agonist activity at human FFA3 in expressed in HEK293 cells assessed as cellular mass movement by dynamic mass redistribution assay	Discovery of a potent and selective free fatty acid receptor 1 agonist with low lipophilicity and high oral bioavailability. — 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_KV14	cAMP Hunter CHO-K1 FFAR3 Gi	Spontaneously immortalized cell line	Female
CVCL_U014	CHO-FFAR3	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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