TAS1R2

Summary

TAS1R2 (taste 1 receptor member 2, HGNC:14905) is a protein-coding gene on chromosome 1p36.13, encoding Taste receptor type 1 member 2 (Q8TE23). Putative taste receptor.

Contributes to sweet taste receptor activity. Involved in detection of chemical stimulus involved in sensory perception of sweet taste and positive regulation of cytokinesis. Part of sweet taste receptor complex.

Source: NCBI Gene 80834 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 179 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_152232

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14905
Approved symbol	TAS1R2
Name	taste 1 receptor member 2
Location	1p36.13
Locus type	gene with protein product
Status	Approved
Aliases	T1R2, TR2
Ensembl gene	ENSG00000179002
Ensembl biotype	protein_coding
OMIM	606226
Entrez	80834

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000375371

RefSeq mRNA: 1 — MANE Select: NM_152232 NM_152232

CCDS: CCDS187

Canonical transcript exons

ENST00000375371 — 6 exons

Exon	Start	End
ENSE00001267288	18841729	18841852
ENSE00001267292	18849341	18849550
ENSE00001267302	18839599	18840527
ENSE00001407872	18857331	18857631
ENSE00001466844	18859479	18859660
ENSE00003497171	18854213	18854986

Expression profiles

Bgee: expression breadth tissue_specific, 5 present calls, max score 38.11.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	38.11	gold quality
skin of leg	UBERON:0001511	37.90	gold quality
sural nerve	UBERON:0015488	37.45	gold quality
lower esophagus mucosa	UBERON:0035834	37.29	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
skeletal muscle tissue	UBERON:0001134	36.66	gold quality
zone of skin	UBERON:0000014	36.65	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow	UBERON:0002371	35.98	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.41	gold quality
skin of abdomen	UBERON:0001416	34.90	gold quality
granulocyte	CL:0000094	34.57	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	34.12	silver quality
muscle tissue	UBERON:0002385	33.47	gold quality
monocyte	CL:0000576	33.31	gold quality
leukocyte	CL:0000738	33.28	gold quality
mucosa of stomach	UBERON:0001199	32.75	gold quality
duodenum	UBERON:0002114	32.49	gold quality
ectocervix	UBERON:0012249	29.94	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.20	gold quality
placenta	UBERON:0001987	29.08	gold quality
metanephros cortex	UBERON:0010533	28.89	gold quality
cortex of kidney	UBERON:0001225	28.61	gold quality
blood	UBERON:0000178	28.59	gold quality
urinary bladder	UBERON:0001255	28.43	gold quality
uterine cervix	UBERON:0000002	27.94	gold quality
lymph node	UBERON:0000029	27.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.65

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 35)

• The mechanism of interaction of the sweet protein monellin with the T1R2-T1R3 receptor. (PMID:12706725)
• sweet and umami taste are strictly dependent on T1R-receptors, and show that selective elimination of T1R-subunits differentially abolishes detection and perception of these two taste modalities (PMID:14636554)
• water rinses remove the inhibitor from the heteromeric sweetener receptor TAS1R2-TAS1R3, which activates cells and results in the perception of strong sweetness from pure water (PMID:16633339)
• Some of the amino acid positions crucial for activation of hTAS1R2+hTAS1R3 by neohesperidin dihydrochalcone are involved in the binding of allosteric modulators in other class C GPCRs (PMID:17935609)
• Interactions between the human sweet-sensing T1R2-T1R3 receptor and sweeteners detected by saturation transfer difference NMR spectroscopy. (PMID:19664591)
• Data show that Positive allosteric modulators of the sweet taste receptor could help reduce the caloric content in food and beverages while maintaining the desired taste. (PMID:20173092)
• Results from mutagenesis and chimeras of the receptor indicated that brazzein interacts with both T1R2 and T1R3 and that the Venus flytrap module of T1R2 is important for brazzein agonism. (PMID:20302879)
• significant associations were seen in TAS1R2 for caries risk and/or protection. (PMID:20858777)
• Our findings show that a genetic variation in TAS1R2 affects habitual consumption of sugars and may contribute to interindividual differences in changing behaviors in response to dietary counseling. (PMID:20943793)
• T1R2/T1R3 is involved in glucose-dependent secretion of satiation peptides (PMID:21540445)
• Genetic ablation of the sweet TR protein T1R2 obliterates fructose-induced insulin release and its potentiating effects on glucose-stimulated insulin secretion in vitro and in vivo. (PMID:22315413)
• associated with caries risk (PMID:23257979)
• Interaction between brazzein and the amino terminal domain of the sweet receptor subunit T1R2 showed a stronger interaction at 7 degrees C than at 37 degrees C.; the low temperature conformation, alters the orientations of 2 loops known to be critical for the sweetness of brazzein, may represent the bound state of brazzei in the complex with the human sweet receptor. (PMID:23349025)
• effects of artificial sweeteners on adipose tissue may be largely independent of the classical sweet taste receptors, T1R2 and T1R3 (PMID:24068707)
• human and mouse membrane trafficking systems for sweet taste receptors T1r2 and T1r3 (PMID:25029362)
• high-risk caries experience (>8 caries) was found to be associated with TAS1R2 rs35874116 homozygous polymorphic genotype. (PMID:25924601)
• no significant associations between GLUT2 and/or TAS1R2 polymorphisms and fillings were found, but allele frequencies of the TAS1R2 variant were marginally significantly different between children with DMFT = 0 and DMFT >/=1. no significant interaction between both genes and risk of dental caries was found. GLUT2 and TASR1 polymorphisms may influence the risk of caries in the Czech population (PMID:26112465)
• The rs12033832 single nucleotide polymorphism in TAS1R2 is associated with sucrose taste and sugar intake, but the effect differs depending on BMI (PMID:26279452)
• In conclusion, the Val/Val genotype of TAS1R2 was associated with a higher carbohydrate intake and HTG. (PMID:26907331)
• The molecular anatomy of sweet taste receptor dimers T1R2-T1R3 has been presented. (PMID:27936499)
• We observe that binding of agonists to VFD2 of TAS1R2 leads to major conformational changes to form a TM6/TM6 interface between TMDs of TAS1R2 and TAS1R3, which is consistent with the activation process observed biophysically on the metabotropic glutamate receptor 2 homodimer. (PMID:28228527)
• Alleles from each TAS1R2 locus (GG compared with AA alleles of rs12033832, and CT/CC compared with TT alleles of rs35874116) were related to higher consumption of carbohydrates (% energy) and higher amount of sweet foods, respectively (P<0.05). (PMID:29110749)
• genetic association studies in population of preschool-aged children in Guelph, Ontario: Data suggest that SNPs in CD36 (rs1761667), TAS1R2 (rs35874116), and TAS2R38 (rs713598) are associated with snacking behavior in the population studied. [PILOT PROJECTS] (PMID:29385734)
• The data further reveal that the C terminus of the extracellular cysteine-rich domain needs to be properly folded for T1R3 dimerization and co-trafficking, but not for surface expression of T1R2 alone. These results guided the modeling of the T1R2-T1R3 dimer in living cells. (PMID:30723160)
• Modeling and Structural Characterization of the Sweet Taste Receptor Heterodimer. (PMID:31553164)
• create several models of the orthosteric binding site of the sweet taste receptor in the hT1R2 VFT domain (PMID:32018080)
• Binding Hotspot and Activation Mechanism of Maltitol and Lactitol toward the Human Sweet Taste Receptor. (PMID:32551626)
• Current Progress in Understanding the Structure and Function of Sweet Taste Receptor. (PMID:32607758)
• Polymorphic variants in Sweet and Umami taste receptor genes and birthweight. (PMID:33654187)
• The Ile191Val is a partial loss-of-function variant of the TAS1R2 sweet-taste receptor and is associated with reduced glucose excursions in humans. (PMID:34509698)
• Relationship between the TAS2R38 and TAS1R2 polymorphisms and the dental status in obese children. (PMID:35510485)
• Functional Characterization of the Venus Flytrap Domain of the Human TAS1R2 Sweet Taste Receptor. (PMID:36012481)
• The rs35874116 single nucleotide polymorphism increases sweet intake and the risk of severe early childhood caries: a case-control study. (PMID:36335309)
• Altered expression levels of TAS1R2 and TAS1R3 genes among SARS-CoV-2 variants of concerns. (PMID:37817023)
• Association between LTF/MMP20/CA6/TAS1R2 polymorphisms and susceptibility to dental caries. (PMID:39212776)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tas1r2.1	ENSDARG00000053135
danio_rerio	tas1r2.2	ENSDARG00000059397
mus_musculus	Tas1r2	ENSMUSG00000028738
rattus_norvegicus	Tas1r2	ENSRNOG00000061876

Paralogs (4): CASR (ENSG00000036828), TAS1R3 (ENSG00000169962), GPRC6A (ENSG00000173612), TAS1R1 (ENSG00000173662)

Protein

Protein identifiers

Taste receptor type 1 member 2 — Q8TE23 (reviewed: Q8TE23)

Alternative names: G-protein coupled receptor 71, Sweet taste receptor T1R2

All UniProt accessions (1): Q8TE23

UniProt curated annotations — full annotation on UniProt →

Function. Putative taste receptor. TAS1R2/TAS1R3 recognizes diverse natural and synthetic sweeteners.

Subunit / interactions. Forms heterodimers with TAS1R3.

Subcellular location. Cell membrane.

Similarity. Belongs to the G-protein coupled receptor 3 family. TAS1R subfamily.

RefSeq proteins (1): NP_689418* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000068	GPCR_3_Ca_sens_rcpt-rel	Family
IPR000337	GPCR_3	Family
IPR001828	ANF_lig-bd_rcpt	Domain
IPR011500	GPCR_3_9-Cys_dom	Domain
IPR017978	GPCR_3_C	Domain
IPR017979	GPCR_3_CS	Conserved_site
IPR028082	Peripla_BP_I	Homologous_superfamily
IPR038550	GPCR_3_9-Cys_sf	Homologous_superfamily

Pfam: PF00003, PF01094, PF07562

UniProt features (32 total): topological domain 8, glycosylation site 8, transmembrane region 7, sequence variant 7, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

25 structures.

PDB	Method	Resolution (Å)
9NOU	ELECTRON MICROSCOPY	2.8
9OPW	ELECTRON MICROSCOPY	2.86
9OQ1	ELECTRON MICROSCOPY	2.98
9NOX	ELECTRON MICROSCOPY	3
9O38	ELECTRON MICROSCOPY	3
9NOW	ELECTRON MICROSCOPY	3.1
9OQ3	ELECTRON MICROSCOPY	3.11
9OPZ	ELECTRON MICROSCOPY	3.16
9UT9	ELECTRON MICROSCOPY	3.18
9OQ2	ELECTRON MICROSCOPY	3.27
9NOV	ELECTRON MICROSCOPY	3.3
9UTC	ELECTRON MICROSCOPY	3.33
9NOR	ELECTRON MICROSCOPY	3.4
9UT8	ELECTRON MICROSCOPY	3.41
9NOS	ELECTRON MICROSCOPY	3.5
9OPY	ELECTRON MICROSCOPY	3.51
9OQ6	ELECTRON MICROSCOPY	3.57
9OQ4	ELECTRON MICROSCOPY	3.59
9UTB	ELECTRON MICROSCOPY	3.59
9OPX	ELECTRON MICROSCOPY	3.63
9OQ0	ELECTRON MICROSCOPY	3.67
9NOY	ELECTRON MICROSCOPY	3.7
9UTA	ELECTRON MICROSCOPY	3.77
9NOT	ELECTRON MICROSCOPY	3.8
9OQ5	ELECTRON MICROSCOPY	3.93

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TE23-F1	86.03	0.50

Antibody-complex structures (SAbDab): 2 — 9NOX, 9O38

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 (8): 84, 248, 292, 312, 368, 428, 487, 527

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-418594	G alpha (i) signalling events
R-HSA-420499	Class C/3 (Metabotropic glutamate/pheromone receptors)
R-HSA-9717207	Sensory perception of sweet, bitter, and umami (glutamate) taste

MSigDB gene sets: 65 (showing top): GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, AAAYRNCTG_UNKNOWN, GOBP_DETECTION_OF_CHEMICAL_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION_OF_TASTE, GOBP_CYTOKINESIS, GOBP_POSITIVE_REGULATION_OF_CELL_DIVISION, GOBP_SENSORY_PERCEPTION_OF_TASTE, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_REGULATION_OF_CYTOKINESIS, GOBP_POSITIVE_REGULATION_OF_CYTOKINESIS, GOBP_REGULATION_OF_CELL_DIVISION, GOBP_DETECTION_OF_STIMULUS, GOBP_SENSORY_PERCEPTION, GOBP_REGULATION_OF_CELL_CYCLE_PROCESS, GOCC_PLASMA_MEMBRANE_SIGNALING_RECEPTOR_COMPLEX

GO Biological Process (6): detection of chemical stimulus involved in sensory perception of sweet taste (GO:0001582), G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of cytokinesis (GO:0032467), sensory perception of sweet taste (GO:0050916), signal transduction (GO:0007165), sensory perception of taste (GO:0050909)

GO Molecular Function (3): G protein-coupled receptor activity (GO:0004930), taste receptor activity (GO:0008527), sweet taste receptor activity (GO:0033041)

GO Cellular Component (4): plasma membrane (GO:0005886), membrane (GO:0016020), signaling receptor complex (GO:0043235), sweet taste receptor complex (GO:1903767)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
GPCR downstream signalling	1
GPCR ligand binding	1
Sensory perception of taste	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
detection of chemical stimulus involved in sensory perception of taste	2
transmembrane signaling receptor activity	2
sensory perception of sweet taste	1
G protein-coupled receptor activity	1
signal transduction	1
cytokinesis	1
regulation of cytokinesis	1
positive regulation of cell division	1
positive regulation of cell cycle process	1
sensory perception of taste	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
sensory perception of chemical stimulus	1
G protein-coupled receptor signaling pathway	1
detection of chemical stimulus involved in sensory perception of sweet taste	1
taste receptor activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1
protein-containing complex	1
taste receptor complex	1

Protein interactions and networks

STRING

1401 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAS1R2	GNAT3	A8MTJ3	987
TAS1R2	TAS1R3	Q7RTX0	986
TAS1R2	SLC5A1	P13866	949
TAS1R2	TAS1R1	Q7RTX1	949
TAS1R2	PLCB2	Q00722	866
TAS1R2	GCG	P01275	850
TAS1R2	TRPM5	Q9NZQ8	827
TAS1R2	TAS2R4	Q9NYW5	820
TAS1R2	FFAR4	Q5NUL3	791
TAS1R2	TAS2R38	P59533	776
TAS1R2	GLP2R	O95838	761
TAS1R2	TAS2R3	Q9NYW6	731
TAS1R2	CALHM1	Q8IU99	691
TAS1R2	PKD2L1	Q9P0L9	688
TAS1R2	GLP1R	P43220	679

IntAct

6 interactions, top by confidence:

A	B	Type	Score
TAS1R3	TAS1R2	psi-mi:“MI:0407”(direct interaction)	0.520
	TAS1R3	psi-mi:“MI:0407”(direct interaction)	0.520
TAS1R2	TAS1R3	psi-mi:“MI:0407”(direct interaction)	0.520
TAS1R2	UPK3BL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (27): TAS1R3 (Affinity Capture-Western), GJC1 (Affinity Capture-MS), SLITRK5 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), GJA1 (Affinity Capture-MS), CANX (Affinity Capture-MS), UPK3BL (Affinity Capture-MS), NMU (Affinity Capture-MS), ADAMTS2 (Affinity Capture-MS), LRFN3 (Affinity Capture-MS), ANO6 (Affinity Capture-MS), ATP11C (Affinity Capture-MS), DHFRL1 (Affinity Capture-MS), LRP12 (Affinity Capture-MS), EDA (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K1Q8, A3QNZ8, A3QNZ9, A3QP00, A3QP01, A3QP07, A3QP08, A3QP09, D4A3T6, E1BPQ3, E9Q4J9, E9Q6I0, G5ECB2, O35659, O62714, O70410, O75899, O88871, P32082, P35384, P41180, P43220, P48442, P48960, Q49HI0, Q58Y75, Q5T6X5, Q5U9X3, Q61606, Q6TAC4, Q70VB1, Q717C1, Q7RTX1, Q80T41, Q8BG22, Q8K385, Q8K4Z6, Q8R420, Q8SQA4, Q8TE23

Diamond homologs: A3QNZ8, A3QNZ9, A3QP00, A3QP01, A3QP07, A3QP08, A3QP09, O62714, P35384, P41180, P48442, Q49HI0, Q7RTX1, Q8TE23, Q923K1, Q925I4, Q99PG6, Q9PW88, Q9QY96, Q9Z0R7, Q9Z0R8, Q49HH9, Q49KI5, E1BPQ3, E9Q6I0, O00222, O15303, O70410, P31421, P31422, P31423, P35349, P35400, P41594, P47743, P70579, Q14416, Q14831, Q14832, Q14833

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	165
Likely benign	10
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1146 predictions. Top by Δscore:

Variant	Effect	Δscore
1:18840525:CAT:C	acceptor_gain	1.0000
1:18840526:ATCT:A	acceptor_loss	1.0000
1:18840527:TC:T	acceptor_loss	1.0000
1:18840528:C:CC	acceptor_gain	1.0000
1:18840528:CTGCA:C	acceptor_loss	1.0000
1:18841723:TCATA:T	donor_loss	1.0000
1:18841724:CATAC:C	donor_loss	1.0000
1:18841726:TAC:T	donor_loss	1.0000
1:18841848:GGGAT:G	acceptor_gain	1.0000
1:18841849:GGAT:G	acceptor_gain	1.0000
1:18841852:TC:T	acceptor_loss	1.0000
1:18841853:C:CA	acceptor_loss	1.0000
1:18841853:C:CC	acceptor_gain	1.0000
1:18843083:CTAT:C	donor_gain	1.0000
1:18843109:CTAT:C	donor_gain	1.0000
1:18843112:T:C	donor_gain	1.0000
1:18843117:T:C	donor_gain	1.0000
1:18843128:A:AC	donor_gain	1.0000
1:18843129:C:CC	donor_gain	1.0000
1:18843129:CT:C	donor_gain	1.0000
1:18843129:CTCTT:C	donor_gain	1.0000
1:18843130:TCTTT:T	donor_gain	1.0000
1:18843131:CTTTC:C	donor_gain	1.0000
1:18843140:T:A	donor_gain	1.0000
1:18849336:CTGA:C	donor_loss	1.0000
1:18849337:TGA:T	donor_loss	1.0000
1:18849338:GA:G	donor_loss	1.0000
1:18849339:A:AC	donor_gain	1.0000
1:18849339:A:C	donor_loss	1.0000
1:18849340:C:CC	donor_gain	1.0000

AlphaMissense

5555 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:18841775:G:C	F515L	0.997
1:18841775:G:T	F515L	0.997
1:18841777:A:G	F515L	0.997
1:18841824:C:G	C499S	0.993
1:18841825:A:T	C499S	0.993
1:18841836:C:G	C495S	0.993
1:18841837:A:T	C495S	0.993
1:18854863:A:G	W203R	0.993
1:18854863:A:T	W203R	0.993
1:18854861:C:A	W203C	0.992
1:18854861:C:G	W203C	0.992
1:18841770:C:G	C517S	0.991
1:18841771:A:T	C517S	0.991
1:18854578:A:G	W298R	0.990
1:18854578:A:T	W298R	0.990
1:18854772:C:G	C233S	0.990
1:18854773:A:T	C233S	0.990
1:18857509:C:T	C102Y	0.990
1:18857516:C:G	D100H	0.990
1:18840515:C:G	C535S	0.989
1:18840516:A:T	C535S	0.989
1:18857508:G:C	C102W	0.989
1:18857509:C:G	C102S	0.989
1:18857510:A:T	C102S	0.989
1:18840490:C:A	W543C	0.988
1:18840490:C:G	W543C	0.988
1:18841776:A:C	F515C	0.988
1:18849359:C:A	W483C	0.988
1:18849359:C:G	W483C	0.988
1:18849449:C:A	W453C	0.988

dbSNP variants (sampled 300 via entrez): RS1000048985 (1:18845921 T>C,G), RS1000072249 (1:18856955 T>C), RS1000088557 (1:18852078 C>G), RS1000131145 (1:18842071 A>G), RS1000140239 (1:18845345 C>A,T), RS1000336195 (1:18847667 C>T), RS1000462739 (1:18840674 A>C,T), RS1000470259 (1:18841142 G>A), RS1000777434 (1:18842432 C>T), RS1000812131 (1:18847897 A>C), RS1000849834 (1:18861631 C>G), RS1001138178 (1:18856153 A>C,G), RS1001234036 (1:18841207 T>C), RS1001263410 (1:18841600 C>A,T), RS1001371387 (1:18856726 G>A,C)

Disease associations

OMIM: gene MIM:606226 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000567_2	Parkinson’s disease	5.000000e-07
GCST001961_1	Anorexia nervosa	9.000000e-06
GCST004881_5	Knee osteoarthritis	7.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1613741 (SINGLE PROTEIN), CHEMBL3832642 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,029 (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
CHEMBL3715108	LACTISOLE SODIUM	1	1,029

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Taste 1 receptors

Binding affinities (BindingDB)

113 measured of 113 human assays (113 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2,3,5,6-tetrafluoro-4-methyl-N-(3-methylbutan-2-yl)benzamide	EC50	140 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
3-chloro-2-hydroxy-N-(2-methyl-1,2,3,4-tetrahydronaphthalen-1-yl)benzamide	EC50	190 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
N-(3,3-dimethylbutan-2-yl)-2,3,5,6-tetrafluoro-4-methylbenzamide	EC50	210 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
N-heptan-4-yl-3-(trifluoromethyl)benzamide	EC50	330 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
N-(2-methylcyclohexyl)-3-(trifluoromethoxy)benzamide	EC50	420 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
3-chloro-5-fluoro-N-(2-methylcyclohexyl)benzamide	EC50	450 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
N-[(2R)-3,3-dimethylbutan-2-yl]-2,3,5,6-tetrafluoro-4-methylbenzamide	EC50	490 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
4-fluoro-N-(2-methylcyclohexyl)-3-(trifluoromethyl)benzamide	EC50	510 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
2,5-dichloro-N-(2-methylcyclohexyl)benzamide	EC50	630 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
3-chloro-2-hydroxy-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]benzamide	EC50	650 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
2,3,5,6-tetrafluoro-N-hexan-2-yl-4-methylbenzamide	EC50	710 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
3,5-dichloro-2,6-dimethoxy-N-(2-methylcyclohexyl)benzamide	EC50	710 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
2,4,6-trimethyl-N-(2-methylcyclohexyl)benzamide	EC50	720 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
3,6-dichloro-2-methoxy-N-(2-methylcyclohexyl)benzamide	EC50	770 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
3,6-dichloro-N-(2-fluorophenyl)-2-methoxybenzamide	EC50	830 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
N-[(2S)-3,3-dimethylbutan-2-yl]-2,3,5,6-tetrafluoro-4-methylbenzamide	EC50	900 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
2,6-dichloro-N-(2-methylcyclohexyl)benzamide	EC50	910 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
N-(4-bromo-2,6-dimethylphenyl)-1,3-dihydroisoindole-2-carboxamide	EC50	930 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
2-chloro-6-methoxy-N-(2-methylcyclohexyl)pyridine-4-carboxamide	EC50	950 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
N-[(2R)-2-bicyclo[2.2.1]heptanyl]-2,3,5,6-tetrafluoro-4-methylbenzamide	EC50	1020 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
3-chloro-2-hydroxy-N-(5-hydroxy-1,2,3,4-tetrahydronaphthalen-1-yl)benzamide	EC50	1030 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
N-(1-methoxybutan-2-yl)-2,4-dimethylbenzamide	EC50	1060 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
N-(2,3-dimethylcyclohexyl)-2,3,5,6-tetrafluoro-4-methylbenzamide	EC50	1080 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
2-chloro-N-(2,3-dimethylcyclohexyl)pyridine-4-carboxamide	EC50	1080 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
N-cyclohexyl-2,3,5,6-tetrafluoro-4-methylbenzamide	EC50	1130 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
N-cyclooctyl-2,3,5,6-tetrafluoro-4-methylbenzamide	EC50	1250 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
2,3,5,6-tetrafluoro-4-methyl-N-[(2R)-3-methylbutan-2-yl]benzamide	EC50	1250 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
3,6-dichloro-N-(2,3-dimethylcyclohexyl)-2-methoxybenzamide	EC50	1290 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
N-(2-methyl-4-nitrophenyl)-1,3-dihydroisoindole-2-carboxamide	EC50	1300 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
N-(2,4-difluorophenyl)-1,3-dihydroisoindole-2-carboxamide	EC50	1370 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
N-cycloheptyl-2,4,6-trimethylbenzamide	EC50	1390 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
N-(2,3-dimethylcyclohexyl)-2,4,6-trimethylbenzamide	EC50	1410 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
N-(2-chloro-4,6-dimethoxyphenyl)-3-(trifluoromethyl)benzamide	EC50	1420 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
3-methyl-N-(2-methyl-1,2,3,4-tetrahydronaphthalen-1-yl)-1,2-oxazole-4-carboxamide	EC50	1480 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
3,5-dichloro-N-(2,4-dimethylphenyl)-4-methoxybenzamide	EC50	1480 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
3-chloro-N-(2,3-dihydro-1H-inden-1-yl)-2-hydroxybenzamide	EC50	1490 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
2-methyl-N-(2-methylcyclohexyl)naphthalene-1-carboxamide	EC50	1520 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
3-chloro-4-fluoro-N-[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]benzamide	EC50	1550 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
3-chloro-2-hydroxy-N-(4-methyl-1,2,3,4-tetrahydronaphthalen-1-yl)benzamide	EC50	1610 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
3-chloro-2-hydroxy-N-(6-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)benzamide	EC50	1610 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
3-chloro-4-fluoro-N-(2-methylcyclohexyl)benzamide	EC50	1700 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
3-chloro-2-hydroxy-N-(1,2,3,4-tetrahydronaphthalen-1-yl)benzamide	EC50	1810 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
3-chloro-4-ethyl-N-(2-methylcyclohexyl)benzamide	EC50	1830 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
3,5-dichloro-4-methoxy-N-(2-methylphenyl)benzamide	EC50	1840 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
5-bromo-N-(2,3-dimethylcyclohexyl)pyridine-3-carboxamide	EC50	1890 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
2-chloro-N-(2-methylcyclohexyl)pyridine-4-carboxamide	EC50	1920 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
2-chloro-3-methyl-N-(2-methylcyclohexyl)benzamide	EC50	1950 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
2,3-dihydroxy-N-(2-methyl-1,2,3,4-tetrahydronaphthalen-1-yl)benzamide	EC50	1980 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
N-(2-methyl-3-nitrophenyl)-1,3-dihydroisoindole-2-carboxamide	EC50	2010 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators
N-cyclopentyl-2,3,5,6-tetrafluoro-4-methylbenzamide	EC50	2230 nM	US-9459250: Use of T1R3 venus flytrap region polypeptide to screen for taste modulators

ChEMBL bioactivities

112 potent at pChembl≥5 of 118 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.85	EC50	140	nM	CHEMBL3717758
6.72	EC50	190	nM	CHEMBL3719110
6.68	EC50	210	nM	CHEMBL3716208
6.38	EC50	420	nM	CHEMBL3715898
6.35	EC50	450	nM	CHEMBL3717965
6.31	EC50	490	nM	CHEMBL3716884
6.29	EC50	510	nM	CHEMBL3717355
6.20	EC50	630	nM	CHEMBL3718788
6.19	EC50	650	nM	CHEMBL3718675
6.15	EC50	710	nM	CHEMBL3716322
6.15	EC50	710	nM	CHEMBL3716963
6.14	EC50	720	nM	CHEMBL3715869
6.11	EC50	770	nM	CHEMBL3718745
6.08	EC50	830	nM	CHEMBL3718115
6.05	EC50	900	nM	CHEMBL3714863
6.04	EC50	910	nM	CHEMBL3718185
6.03	EC50	930	nM	CHEMBL3718359
6.02	EC50	950	nM	CHEMBL3717822
5.99	EC50	1030	nM	CHEMBL3714969
5.99	EC50	1020	nM	CHEMBL3717454
5.97	EC50	1060	nM	CHEMBL3716690
5.97	EC50	1080	nM	CHEMBL3715683
5.97	EC50	1080	nM	CHEMBL3717908
5.95	EC50	1130	nM	CHEMBL3718002
5.90	EC50	1250	nM	CHEMBL3719314
5.90	EC50	1250	nM	CHEMBL3716611
5.89	EC50	1290	nM	CHEMBL3715567
5.89	EC50	1300	nM	CHEMBL3718821
5.86	EC50	1390	nM	CHEMBL3715531
5.86	EC50	1370	nM	CHEMBL3716237
5.85	EC50	1410	nM	CHEMBL3716243
5.85	EC50	1420	nM	CHEMBL3717480
5.83	EC50	1480	nM	CHEMBL3717306
5.83	EC50	1490	nM	CHEMBL3718729
5.83	EC50	1480	nM	CHEMBL3714994
5.82	EC50	1520	nM	CHEMBL3718386
5.81	EC50	1550	nM	CHEMBL3718206
5.79	EC50	1610	nM	CHEMBL3717736
5.79	EC50	1610	nM	CHEMBL3715669
5.77	EC50	1700	nM	CHEMBL3715694
5.74	EC50	1810	nM	CHEMBL3715666
5.74	EC50	1830	nM	CHEMBL3717721
5.74	EC50	1840	nM	CHEMBL3715452
5.72	EC50	1890	nM	CHEMBL3719365
5.72	EC50	1920	nM	CHEMBL3717269
5.71	EC50	1950	nM	CHEMBL3715850
5.70	EC50	1980	nM	CHEMBL3715027
5.70	EC50	2010	nM	CHEMBL3715180
5.65	EC50	2230	nM	CHEMBL3715979
5.63	EC50	2360	nM	CHEMBL3718446

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aspartame	affects binding, increases activity, increases reaction, decreases reaction	5
neotame	affects binding, increases activity	3
trichlorosucrose	affects binding, increases activity	2
lactisole	affects binding, decreases reaction, increases activity	2
Cyclamates	affects binding, increases activity, decreases reaction	2
aristolochic acid I	increases expression	1
neohesperidin dihydrochalcone	affects binding, decreases reaction, increases activity	1
1-chlorosucrose	affects binding, increases activity	1
1,6-dichlorosucrose	affects binding, increases activity	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
CGP 52608	increases reaction, affects binding	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Glucose	affects binding, increases reaction	1
Plant Extracts	affects cotreatment, decreases expression	1
Sucrose	affects binding, increases activity	1
Sweetening Agents	affects binding, increases activity	1
Asbestos, Crocidolite	affects expression	1

ChEMBL screening assays

30 unique, capped per target: 15 functional, 15 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3720946	Functional	Activity at human T1R2 Y218A mutant assessed as calcium response by fluo-4-AM dye based FLIPR assay	T1R hetero-oligomeric taste receptors, cell lines that express said receptors, and taste compounds
CHEMBL1072438	Binding	Activity at human T1R2/T1R3 expressed in HEK293T cells co-expressing Galpha-16-gust44 assessed as F340/F380 ratio at 1.25 mM	Photoactive ligands probing the sweet taste receptor. Design and synthesis of highly potent diazirinyl D-phenylalanine derivatives. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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