BRS3

Summary

BRS3 (bombesin receptor subtype 3, HGNC:1113) is a protein-coding gene on chromosome Xq26.3, encoding Bombesin receptor subtype-3 (P32247). Role in sperm cell division, maturation, or function.

The protein encoded by this gene is a G protein-coupled membrane receptor that binds bombesin-like peptides. This binding results in activation of a phosphatidylinositol-calcium second messenger system, with physiological effects including regulation of metabolic rate, glucose metabolism, and hypertension.

Source: NCBI Gene 680 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 58 total — 1 pathogenic
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001727

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1113
Approved symbol	BRS3
Name	bombesin receptor subtype 3
Location	Xq26.3
Locus type	gene with protein product
Status	Approved
Aliases	BB3, BB3R, BBR3
Ensembl gene	ENSG00000102239
Ensembl biotype	protein_coding
OMIM	300107
Entrez	680

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000370648

RefSeq mRNA: 1 — MANE Select: NM_001727 NM_001727

CCDS: CCDS14656

Canonical transcript exons

ENST00000370648 — 3 exons

Exon	Start	End
ENSE00000677000	136490133	136490484
ENSE00001453226	136491962	136493780
ENSE00001453228	136487947	136488548

Expression profiles

Bgee: expression breadth broad, 48 present calls, max score 90.23.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0522 / max 52.5991, expressed in 6 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197689	0.0282	3
197690	0.0150	3
197688	0.0091	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	90.23	gold quality
corpus epididymis	UBERON:0004359	90.12	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.32	gold quality
caput epididymis	UBERON:0004358	70.14	gold quality
pancreatic ductal cell	CL:0002079	69.71	silver quality
diaphragm	UBERON:0001103	66.62	gold quality
islet of Langerhans	UBERON:0000006	66.10	gold quality
epithelial cell of pancreas	CL:0000083	65.31	silver quality
cauda epididymis	UBERON:0004360	62.94	silver quality
type B pancreatic cell	CL:0000169	62.50	gold quality
hair follicle	UBERON:0002073	62.40	gold quality
tongue squamous epithelium	UBERON:0006919	58.25	gold quality
tibialis anterior	UBERON:0001385	58.03	silver quality
right ovary	UBERON:0002118	57.13	gold quality
decidua	UBERON:0002450	56.55	gold quality
left uterine tube	UBERON:0001303	54.19	gold quality
quadriceps femoris	UBERON:0001377	53.94	gold quality
endothelial cell	CL:0000115	53.36	gold quality
nucleus accumbens	UBERON:0001882	53.07	gold quality
vastus lateralis	UBERON:0001379	52.64	gold quality
triceps brachii	UBERON:0001509	52.59	gold quality
deltoid	UBERON:0001476	52.49	gold quality
male germ cell	CL:0000015	51.81	gold quality
sperm	CL:0000019	51.63	gold quality
nasal cavity epithelium	UBERON:0005384	51.33	gold quality
left ventricle myocardium	UBERON:0006566	51.22	gold quality
thymus	UBERON:0002370	50.55	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.78

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARA, PPARG, TFAP2A

Literature-anchored findings (GeneRIF, showing 15)

• results indicate that the sequence variation in the E3 loop is responsible for the species difference between rat and human BRS-3, and multiple residues in the E3 loop are involved in interactions with the agonist dY-bombesin (PMID:12102638)
• Study found that the BRS-3 agonist stimulated adhesion of NCI-N417 cells in laminin-coated culture wells suggesting that BRS-3 may be involved in invasion and metastasis of certain cancer cells (PMID:16979789)
• Data suggest that activator protein 2alpha and peroxisome-proliferator-activated receptor alpha may be especially involved in the ozone-inducible up-regulation mechanism of bombesin receptor subtype 3 expression. (PMID:17355223)
• The secretion of TGF-beta1 increased and the synthesis of PGE2 decreased from BRS-3-activated BEC, which were correlated with the proliferation and collagen synthesis of HLF. (PMID:17714959)
• These results identify a potential role for BRS-3 in islet physiology, with agonism directly promoting glucose-stimulated insulin secretion (PMID:21878513)
• BRS-3 agonist-dependent signaling mediates CREB phosphorylation and transactivation through protein kinase (PK)A, (PK)C, and mitogen-activated protein/extracellular regulated kinase kinase (MEK)-1 pathways. (PMID:22127929)
• BRS-3 plays an important role in glucose metabolism. (PMID:23291341)
• The role of the human BRS-3 receptor in glucose homeostasis. (PMID:24220502)
• Data show that gastrin-releasing peptide receptor/bombesin receptor subtype-3 positive cells and protein expression in tumors decreased by treatment with RC-3095 or gemcitabine alone or greater in combination. (PMID:24326363)
• High BRS3 expression is associated with liver metastases of pancreas neuroendocrine tumors. (PMID:25241033)
• mammalian homologue of CCHa2-R, Bombesin receptor subtype-3 (Brs3), is an orphan receptor that is expressed in the islet beta-cells (PMID:26020940)
• BRS-3 and EP3 interact to potentiate PGE2 signaling. This potentiating effect is receptor specific, and it occurs only when BRS-3 is paired to EP3. (PMID:29401613)
• BRS-3 protein levels were decreased in diabetic rat and in obese and diabetic human fat pieces. (PMID:29402494)
• These results suggest that human BRS-3, similar to GRPR/NMBR, is frequently ectopically-expressed by lung-cancer cells in which, it is functional, affecting cell signaling/growth. (PMID:29410320)
• Agonist-induced extracellular vesicles contribute to the transfer of functional bombesin receptor-subtype 3 to recipient cells. (PMID:35032194)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Brs3	ENSMUSG00000031130
rattus_norvegicus	Brs3	ENSRNOG00000000873
drosophila_melanogaster	CCHa2-R	FBGN0033058
drosophila_melanogaster	CCHa1-R	FBGN0050106

Paralogs (15): NTSR1 (ENSG00000101188), MLNR (ENSG00000102539), GHSR (ENSG00000121853), GRPR (ENSG00000126010), NMUR2 (ENSG00000132911), NMBR (ENSG00000135577), EDNRB (ENSG00000136160), EDNRA (ENSG00000151617), NTSR2 (ENSG00000169006), GPR37L1 (ENSG00000170075), GPR37 (ENSG00000170775), NMUR1 (ENSG00000171596), GPR148 (ENSG00000173302), TRHR (ENSG00000174417), GPR39 (ENSG00000183840)

Protein

Protein identifiers

Bombesin receptor subtype-3 — P32247 (reviewed: P32247)

All UniProt accessions (1): P32247

UniProt curated annotations — full annotation on UniProt →

Function. Role in sperm cell division, maturation, or function. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.

Subunit / interactions. Interacts with C6orf89.

Subcellular location. Cell membrane.

Tissue specificity. In germ cells in testis. Lung carcinoma cells.

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

RefSeq proteins (1): NP_001718* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR001556	Bombsn_rcpt-like	Family
IPR001560	Bombesin_rcpt_3	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (37 total): helix 12, topological domain 8, transmembrane region 7, glycosylation site 2, sequence variant 2, strand 2, chain 1, lipid moiety-binding region 1, disulfide bond 1, turn 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
9K07	ELECTRON MICROSCOPY	2.83
8Y52	ELECTRON MICROSCOPY	2.9
9M0J	ELECTRON MICROSCOPY	2.9
8Y53	ELECTRON MICROSCOPY	2.93
9LWP	ELECTRON MICROSCOPY	2.93
8Y51	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P32247-F1	79.70	0.56

Antibody-complex structures (SAbDab): 1 — 8Y51

Functional residue map

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

Post-translational modifications (1): 347

Disulfide bonds (1): 120–203

Glycosylation sites (2): 10, 18

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-416476	G alpha (q) signalling events
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 76 (showing top): GOBP_BEHAVIOR, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_ADULT_BEHAVIOR, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, BLALOCK_ALZHEIMERS_DISEASE_UP, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_GLUCOSE_METABOLIC_PROCESS, AFP1_Q6, GOMF_PEPTIDE_RECEPTOR_ACTIVITY, AACTTT_UNKNOWN, POU3F2_02, GOBP_MONOSACCHARIDE_METABOLIC_PROCESS

GO Biological Process (7): glucose metabolic process (GO:0006006), G protein-coupled receptor signaling pathway (GO:0007186), regulation of blood pressure (GO:0008217), adult feeding behavior (GO:0008343), signal transduction (GO:0007165), neuropeptide signaling pathway (GO:0007218), bombesin receptor signaling pathway (GO:0031989)

GO Molecular Function (4): bombesin receptor activity (GO:0004946), neuropeptide receptor activity (GO:0008188), G protein-coupled receptor activity (GO:0004930), G protein-coupled peptide receptor activity (GO:0008528)

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

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Signaling by GPCR	2
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1
Signal Transduction	1
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	3
G protein-coupled receptor activity	2
hexose metabolic process	1
signal transduction	1
blood circulation	1
regulation of biological quality	1
feeding behavior	1
adult behavior	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
neuropeptide receptor activity	1
bombesin receptor signaling pathway	1
neuropeptide signaling pathway	1
G protein-coupled peptide receptor activity	1
neuropeptide binding	1
transmembrane signaling receptor activity	1
peptide receptor activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

822 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BRS3	GRP	P07491	977
BRS3	CCDC80	Q76M96	917
BRS3	NMB	P08949	896
BRS3	SRPX	P78539	840
BRS3	C6orf89	Q6UWU4	810
BRS3	NTS	P30990	554
BRS3	SCN3B	Q9NY72	521
BRS3	GNG8	Q9UK08	510
BRS3	SYTL4	Q96C24	492
BRS3	GPD1L	Q8N335	489
BRS3	VIP	P01282	487
BRS3	SCN1B	Q07699	485
BRS3	ALDH18A1	P54886	474
BRS3	GABRR3	A8MPY1	449
BRS3	CACNA2D1	P54289	447

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A2L0VBG2, A1ZAX0, B2ZHY2, O43194, O43614, O46635, O46639, O54798, O62809, O93603, O97967, P08909, P14842, P18599, P20789, P21761, P28223, P28335, P30975, P32247, P32940, P34968, P34981, P35363, P35371, P41984, P47751, P50128, P50129, P56490, P56719, P58308, Q01717, Q28596, Q4V622, Q5IS53, Q5IS66, Q5IS98, Q5R4Q6, Q5U431

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	38
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3245190	NC_000023.10:g.(?135288592)(135741574_?)del	Pathogenic

SpliceAI

455 predictions. Top by Δscore:

Variant	Effect	Δscore
X:136488549:G:GG	donor_gain	0.9800
X:136488550:T:A	donor_loss	0.9800
X:136490245:GC:G	donor_gain	0.9600
X:136488544:GACAG:G	donor_gain	0.9500
X:136490259:T:G	donor_gain	0.9500
X:136488471:TTGTA:T	donor_gain	0.9300
X:136490131:A:AG	acceptor_gain	0.9300
X:136490132:G:GG	acceptor_gain	0.9300
X:136488470:GTT:G	donor_gain	0.9200
X:136488511:GTGTC:G	donor_gain	0.9200
X:136491599:GTAA:G	acceptor_gain	0.9200
X:136488461:G:GT	donor_gain	0.9100
X:136488469:GGTT:G	donor_gain	0.9000
X:136488470:GTTG:G	donor_gain	0.9000
X:136488547:AG:A	donor_gain	0.9000
X:136488548:GG:G	donor_gain	0.9000
X:136490131:A:C	acceptor_loss	0.8900
X:136488546:CAG:C	donor_gain	0.8700
X:136488551:GAGT:G	donor_loss	0.8200
X:136491598:A:AG	acceptor_gain	0.8100
X:136491599:G:GG	acceptor_gain	0.8100
X:136491961:GATT:G	acceptor_gain	0.8100
X:136488545:ACAG:A	donor_gain	0.8000
X:136488512:T:A	donor_gain	0.7900
X:136490482:CAGG:C	donor_loss	0.7900
X:136490483:AGGT:A	donor_loss	0.7900
X:136490484:GGTA:G	donor_loss	0.7900
X:136490485:G:GA	donor_loss	0.7900
X:136490486:TA:T	donor_loss	0.7900
X:136490122:T:G	acceptor_gain	0.7600

AlphaMissense

2594 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:136488376:A:C	S88R	0.999
X:136488378:C:A	S88R	0.999
X:136488378:C:G	S88R	0.999
X:136488392:A:C	D93A	0.999
X:136488538:A:C	S142R	0.999
X:136488540:C:A	S142R	0.999
X:136488540:C:G	S142R	0.999
X:136488295:G:C	G61R	0.998
X:136488309:T:A	N65K	0.998
X:136488309:T:G	N65K	0.998
X:136488392:A:G	D93G	0.998
X:136488392:A:T	D93V	0.998
X:136490212:T:A	W172R	0.998
X:136490212:T:C	W172R	0.998
X:136490384:C:G	P229R	0.998
X:136492013:T:C	F280L	0.998
X:136492015:T:A	F280L	0.998
X:136492015:T:G	F280L	0.998
X:136488296:G:A	G61D	0.997
X:136488304:G:A	G64R	0.997
X:136488304:G:C	G64R	0.997
X:136488380:T:C	L89P	0.997
X:136488391:G:C	D93H	0.997
X:136488393:T:A	D93E	0.997
X:136488393:T:G	D93E	0.997
X:136488536:T:C	L141P	0.997
X:136490420:C:A	A241D	0.997
X:136492161:C:A	A329D	0.997
X:136492184:T:C	F337L	0.997
X:136492186:C:A	F337L	0.997

dbSNP variants (sampled 300 via entrez): RS1000432052 (X:136488672 G>A,C), RS1001041241 (X:136487812 A>G), RS1001536047 (X:136486857 G>A), RS1002810040 (X:136486677 C>T), RS1003047849 (X:136493197 C>G), RS1003646058 (X:136493672 T>C), RS1004999274 (X:136486045 G>A), RS1006052588 (X:136488739 C>T), RS1006920654 (X:136488374 C>A,T), RS1007299289 (X:136487890 C>T), RS1008051737 (X:136493906 C>A), RS1008326455 (X:136492294 C>A), RS1008681731 (X:136489607 C>G,T), RS1009008183 (X:136486007 A>T), RS1009961071 (X:136494157 T>C)

Disease associations

OMIM: gene MIM:300107 | disease phenotypes: MIM:300696

GenCC curated gene-disease

Mondo (1): X-linked myopathy with postural muscle atrophy (MONDO:0010401)

Orphanet (1): X-linked myopathy with postural muscle atrophy (Orphanet:178461)

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 (2): CHEMBL4080 (SINGLE PROTEIN), CHEMBL4524010 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 52,984 (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
CHEMBL1503	OMEPRAZOLE	4	52,284
CHEMBL892	UFIPRAZOLE	2	700

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Bombesin receptors

Most potent curated ligand interactions (26 total), top 25:

Ligand	Action	Affinity	Parameter
compound 21b [PMID: 12723954]	Full agonist	10.2	pEC50
[125I]bantag-1	Antagonist	9.58	pKi
compound 8a [PMID: 24900283]	Agonist	8.85	pIC50
[D-Tyr6,Apa-4Cl11,Phe13,Nle14]bombesin-(6-14)	Full agonist	8.85	pIC50
compound 9g [PMID: 24412111]	Agonist	8.77	pEC50
bantag-1	Antagonist	8.7	pIC50
[3H]bag-2	Agonist	8.59	pKd
MK-7725	Agonist	8.52	pIC50
MK-5046	Agonist	8.43	pKi
dimethyl shikonin oxime 5a	Agonist	8.42	pEC50
[125I][D-Tyr6,β-Ala11,Phe13,Nle14]bombesin-(6-14)	Full agonist	8.4	pKd
[D-Phe6,β-Ala11,Phe13,Nle14]bombesin-(6-14)	Full agonist	8.38	pKi
[D-Tyr6,(R)-APA11,Phe13,Nle14]bombesin-(6-14)	Full agonist	8.37	pIC50
compound 17c [PMID: 25497965]	Agonist	7.92	pEC50
compound 9f [PMID: 24412111]	Agonist	7.77	pEC50
bag-1	Agonist	7.74	pIC50
compound 22e [PMID: 20167483]	Agonist	7.6	pIC50
Ac-Phe-Trp-Ala-His(τBZL)-Nip-Gly-Arg-NH2	Full agonist	7.31	pIC50
bag-2	Agonist	7.02	pIC50
oridonin	Agonist	6.62	pEC50
compound A [PMID: 28324017]	Agonist	6.6	pEC50
licoisoflavone A	Antagonist	6.15	pIC50
NMU (104-114)	Agonist	5.66	pEC50
D-Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-Nal-NH2	Antagonist	5.6	pIC50
phenylacetyl-Ala,DTrp-phenthylamide	Full agonist	5.5	pIC50

Binding affinities (BindingDB)

32 measured of 47 human assays (47 total across all organisms); most potent 32 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
NSC_0	KI	0.82 nM
NSC_0	KI	2.3 nM
NSC_0	KI	2.8 nM
NSC_0	KI	8.2 nM
DPhe6,BetaAla11,Phe13,Nle14-Bn(6-14)	KI	8.9 nM
NSC_0	KI	12.3 nM
NSC_0	KI	15.8 nM
NSC_0	KI	24 nM
NSC_0	KI	85 nM
NSC_0	KI	107 nM
CHEMBL1762252	EC50	220 nM
NSC_0	KI	490 nM
NSC_0	KI	708 nM
NSC_0	KI	776 nM
DPhe6-Bn(6-13)propylamide	KI	1900 nM
NSC_5748287	KI	2100 nM
Substance P(4-11),[Dpro4,Dtrp7,9,10]	KI	2300 nM
NSC_0	KI	2400 nM
H-Nal-cyclo[DCys-Tyr-DTrp-Lys-Val-Cys]-Nal-NH2	KI	2800 nM
CAS_125988	KI	3100 nM
DPhe6-Bn(6-13)hexylamide	KI	3200 nM
CAS_31078-12-3	KI	3600 nM
CAS_5486808	KI	4100 nM
Xenopus NMB	KI	4800 nM
DTyr6,DAla11-Bn(6-13)butylamide	KI	5300 nM
DPhe6-Bn(6-13)methylester	KI	5300 nM
PG-L	KI	5300 nM
Leu8-phyllolitorin	KI	5400 nM
Bombesin,Phe13	KI	6600 nM
CAS_29451-71-6	KI	6900 nM
CAS_31362-50-2	KI	7100 nM

ChEMBL bioactivities

516 potent at pChembl≥5 of 517 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.72	EC50	0.19	nM	CHEMBL57104
9.68	EC50	0.2109	nM	CHEMBL1672354
9.53	EC50	0.2931	nM	CHEMBL1672354
9.44	Ki	0.36	nM	CHEMBL525577
9.30	IC50	0.5	nM	CHEMBL2023112
9.30	IC50	0.5	nM	CHEMBL2023113
9.22	IC50	0.6	nM	CHEMBL2023111
9.15	IC50	0.7	nM	CHEMBL2164581
9.15	IC50	0.7	nM	CHEMBL2179918
9.12	IC50	0.76	nM	CHEMBL2164577
9.05	IC50	0.9	nM	CHEMBL2164223
9.05	IC50	0.9	nM	CHEMBL2179911
9.05	EC50	0.9	nM	CHEMBL4435571
9.00	EC50	1	nM	CHEMBL4461212
8.96	IC50	1.1	nM	CHEMBL2164580
8.96	IC50	1.1	nM	UNIVERSAL LIGAND
8.96	IC50	1.11	nM	CHEMBL6102759
8.92	IC50	1.2	nM	CHEMBL2164582
8.92	IC50	1.2	nM	CHEMBL2179908
8.89	EC50	1.3	nM	CHEMBL3115400
8.85	IC50	1.4	nM	CHEMBL2023110
8.85	IC50	1.4	nM	CHEMBL2164578
8.85	IC50	1.4	nM	CHEMBL2164575
8.85	EC50	1.4	nM	CHEMBL2023109
8.85	EC50	1.4	nM	CHEMBL56369
8.82	EC50	1.5	nM	CHEMBL57438
8.80	IC50	1.6	nM	CHEMBL2179473
8.80	EC50	1.6	nM	CHEMBL3115386
8.77	IC50	1.7	nM	CHEMBL2164224
8.77	EC50	1.7	nM	CHEMBL3115390
8.77	EC50	1.7	nM	CHEMBL3115388
8.76	IC50	1.72	nM	CHEMBL2164576
8.72	IC50	1.9	nM	CHEMBL2164222
8.70	EC50	2	nM	CHEMBL4448589
8.68	IC50	2.1	nM	CHEMBL2023114
8.68	EC50	2.1	nM	CHEMBL3144501
8.66	IC50	2.2	nM	CHEMBL2179916
8.66	EC50	2.2	nM	CHEMBL294647
8.56	IC50	2.773	nM	CHEMBL5406411
8.54	EC50	2.9	nM	CHEMBL57039
8.52	EC50	3	nM	CHEMBL4580739
8.52	EC50	3	nM	CHEMBL4593256
8.52	IC50	3	nM	CHEMBL5924965
8.51	EC50	3.1	nM	CHEMBL57559
8.49	IC50	3.2	nM	CHEMBL2179912
8.48	IC50	3.3	nM	CHEMBL2179476
8.47	EC50	3.4	nM	CHEMBL3356412
8.44	IC50	3.6	nM	CHEMBL2023109
8.44	EC50	3.6	nM	CHEMBL3115399
8.43	Ki	3.7	nM	CHEMBL1672354

PubChem BioAssay actives

498 with measured affinity, of 786 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
2-[[[2-(4-chlorophenyl)acetyl]amino]carbamoylamino]-3-(1H-indol-3-yl)-N-(2-phenylethyl)propanamide	42107: Effective concentration required against human bombesin receptor 3 (BRS-3) in CHO cells by using FLIPR assay.	ec50	0.0002	uM
(2S)-1,1,1-trifluoro-2-(4-pyrazol-1-ylphenyl)-3-[5-[[1-(trifluoromethyl)cyclopropyl]methyl]-1H-imidazol-2-yl]propan-2-ol	1990901: Agonist activity at human BB3 stably overexpressed in human NCI-H1299 cells assessed as increase in IP-1 accumulation incubated for 60 mins by HTRF assay	ec50	0.0002	uM
(2S)-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxohexan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-2-[[(2R)-2-amino-3-phenylpropanoyl]amino]pentanediamide	348843: Binding affinity to BRS-3 receptor	ki	0.0004	uM
2-methyl-2-[6-[4-(trifluoromethoxy)phenyl]sulfonyl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-7-yl]propanamide	660675: Displacement of 125I-dY-peptide from human BRS3 expressed in NFAT-CHO cells after 2 hrs by liquid scintillation counting	ic50	0.0005	uM
1-[6-[4-(trifluoromethoxy)phenyl]sulfonyl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-7-yl]cyclobutane-1-carboxamide	660675: Displacement of 125I-dY-peptide from human BRS3 expressed in NFAT-CHO cells after 2 hrs by liquid scintillation counting	ic50	0.0005	uM
2-[3-[1-[6-[4-(trifluoromethoxy)phenyl]sulfonyl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-7-yl]cyclobutyl]-1,2,4-oxadiazol-5-yl]propan-2-ol	660675: Displacement of 125I-dY-peptide from human BRS3 expressed in NFAT-CHO cells after 2 hrs by liquid scintillation counting	ic50	0.0006	uM
10-(4-tert-butylphenyl)sulfonyl-5-(trifluoromethyl)-2,4,10,16-tetrazatetracyclo[9.8.0.03,8.012,17]nonadeca-1(11),3(8),4,6,12(17),13,15,18-octaene	704738: Displacement of [125I]-[D-Tyr6,beta-Ala11,Phe13,Nle14]-Bombesin(6-14) from human BRS3 expressed in CHO cells expressing NFAT after 2 hrs by liquid scintillation counting	ic50	0.0007	uM
[3-[6-(4-tert-butylphenyl)sulfonyl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-7-yl]-1,2,4-oxadiazol-5-yl]methanol	696984: Displacement of [125I]-dY-peptide from human BRS-3 expressed in NFAT-CHO cells after 2 hrs by by liquid scintillation counting	ic50	0.0007	uM
6-(4-tert-butylphenyl)sulfonyl-7-(1-methylpyrazol-4-yl)-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepine	696984: Displacement of [125I]-dY-peptide from human BRS-3 expressed in NFAT-CHO cells after 2 hrs by by liquid scintillation counting	ic50	0.0008	uM
2-[4-[2-[5-(2,2-dimethylpropyl)-1-[2-(3-hydroxyphenoxy)ethyl]imidazol-2-yl]ethyl]phenyl]-6-fluorobenzoic acid	1628045: Agonist activity at human BRS3 expressed in CHOK1 cells measured after 1 hrs by IP-One HTRF assay	ec50	0.0009	uM
2-[3-[6-(4-tert-butylphenyl)sulfonyl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-7-yl]-1,2,4-oxadiazol-5-yl]propan-2-ol	696984: Displacement of [125I]-dY-peptide from human BRS-3 expressed in NFAT-CHO cells after 2 hrs by by liquid scintillation counting	ic50	0.0009	uM
6-(4-tert-butylphenyl)sulfonyl-7-methyl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepine	704738: Displacement of [125I]-[D-Tyr6,beta-Ala11,Phe13,Nle14]-Bombesin(6-14) from human BRS3 expressed in CHO cells expressing NFAT after 2 hrs by liquid scintillation counting	ic50	0.0009	uM
3-[5-(2,2-dimethylpropyl)-2-[2-[4-(3-fluoro-2-methoxycarbonylphenyl)phenyl]ethyl]imidazol-1-yl]propanoic acid	1628045: Agonist activity at human BRS3 expressed in CHOK1 cells measured after 1 hrs by IP-One HTRF assay	ec50	0.0010	uM
(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxohexan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide	242051: Inhibition of bombesin subtype 3 receptor expressed in human lung carcinoids	ic50	0.0011	uM
3-[6-(4-tert-butylphenyl)sulfonyl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-7-yl]-1,2,4-oxadiazole	696984: Displacement of [125I]-dY-peptide from human BRS-3 expressed in NFAT-CHO cells after 2 hrs by by liquid scintillation counting	ic50	0.0011	uM
6-(4-tert-butylphenyl)sulfonyl-2-chloro-7,8-dimethyl-5,11-dihydropyrido[3,2-c][1,5]benzodiazepine	704738: Displacement of [125I]-[D-Tyr6,beta-Ala11,Phe13,Nle14]-Bombesin(6-14) from human BRS3 expressed in CHO cells expressing NFAT after 2 hrs by liquid scintillation counting	ic50	0.0012	uM
(1S)-1-[3-[6-(4-tert-butylphenyl)sulfonyl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-7-yl]-1,2,4-oxadiazol-5-yl]ethanol	696984: Displacement of [125I]-dY-peptide from human BRS-3 expressed in NFAT-CHO cells after 2 hrs by by liquid scintillation counting	ic50	0.0012	uM
2-[3-(4-methylphenoxy)phenyl]-1-[8-(trifluoromethyl)-1,2,3,5-tetrahydropyrido[2,3-e][1,4]diazepin-4-yl]ethanone	1069137: Agonist activity at human BRS-3 expressed in CHOK1 cells after 1 hr by HTRF assay	ec50	0.0013	uM
3-(1H-indol-3-yl)-N-(2-phenylethyl)-2-[[(2-pyridin-3-ylacetyl)amino]carbamoylamino]propanamide	42107: Effective concentration required against human bombesin receptor 3 (BRS-3) in CHO cells by using FLIPR assay.	ec50	0.0014	uM
2-[3-[6-[4-(trifluoromethoxy)phenyl]sulfonyl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-7-yl]-1,2,4-oxadiazol-5-yl]propan-2-ol	1069137: Agonist activity at human BRS-3 expressed in CHOK1 cells after 1 hr by HTRF assay	ec50	0.0014	uM
6-(4-tert-butylphenyl)sulfonyl-7,8-dimethyl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepine	704738: Displacement of [125I]-[D-Tyr6,beta-Ala11,Phe13,Nle14]-Bombesin(6-14) from human BRS3 expressed in CHO cells expressing NFAT after 2 hrs by liquid scintillation counting	ic50	0.0014	uM
2-[3-[2-[6-[4-(trifluoromethoxy)phenyl]sulfonyl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-7-yl]propan-2-yl]-1,2,4-oxadiazol-5-yl]propan-2-ol	660675: Displacement of 125I-dY-peptide from human BRS3 expressed in NFAT-CHO cells after 2 hrs by liquid scintillation counting	ic50	0.0014	uM
6-(4-tert-butylphenyl)sulfonyl-7-piperidin-4-yl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepine	696984: Displacement of [125I]-dY-peptide from human BRS-3 expressed in NFAT-CHO cells after 2 hrs by by liquid scintillation counting	ic50	0.0014	uM
2-[[(E)-furan-2-ylmethylideneamino]carbamoylamino]-3-(1H-indol-3-yl)-N-(2-phenylethyl)propanamide	42107: Effective concentration required against human bombesin receptor 3 (BRS-3) in CHO cells by using FLIPR assay.	ec50	0.0015	uM
7,8-dimethyl-6-(4-propan-2-ylphenyl)sulfonyl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepine	704738: Displacement of [125I]-[D-Tyr6,beta-Ala11,Phe13,Nle14]-Bombesin(6-14) from human BRS3 expressed in CHO cells expressing NFAT after 2 hrs by liquid scintillation counting	ic50	0.0016	uM
2-[(5R)-4-[2-(3-phenoxyphenyl)acetyl]-8-(trifluoromethyl)-1,2,3,5-tetrahydropyrido[2,3-e][1,4]diazepin-5-yl]acetic acid	1069137: Agonist activity at human BRS-3 expressed in CHOK1 cells after 1 hr by HTRF assay	ec50	0.0016	uM
2-[3-[6-(4-propan-2-ylphenyl)sulfonyl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-7-yl]-1,2,4-oxadiazol-5-yl]propan-2-ol	696984: Displacement of [125I]-dY-peptide from human BRS-3 expressed in NFAT-CHO cells after 2 hrs by by liquid scintillation counting	ic50	0.0017	uM
6-(4-tert-butylphenyl)sulfonyl-7-pyridin-3-yl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepine	696984: Displacement of [125I]-dY-peptide from human BRS-3 expressed in NFAT-CHO cells after 2 hrs by by liquid scintillation counting	ic50	0.0017	uM
2-[(5R)-4-[2-[3-[(6-methyl-3-pyridinyl)oxy]phenyl]acetyl]-8-(trifluoromethyl)-1,2,3,5-tetrahydropyrido[2,3-e][1,4]diazepin-5-yl]acetic acid	1069137: Agonist activity at human BRS-3 expressed in CHOK1 cells after 1 hr by HTRF assay	ec50	0.0017	uM
2-[(5R)-4-[2-[3-(4-fluorophenoxy)phenyl]acetyl]-8-(trifluoromethyl)-1,2,3,5-tetrahydropyrido[2,3-e][1,4]diazepin-5-yl]acetic acid	1069137: Agonist activity at human BRS-3 expressed in CHOK1 cells after 1 hr by HTRF assay	ec50	0.0017	uM
(1R)-1-[3-[6-(4-tert-butylphenyl)sulfonyl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-7-yl]-1,2,4-oxadiazol-5-yl]ethanol	696984: Displacement of [125I]-dY-peptide from human BRS-3 expressed in NFAT-CHO cells after 2 hrs by by liquid scintillation counting	ic50	0.0019	uM
2-[4-[2-[5-(2,2-dimethylpropyl)-1-[2-(methanesulfonamido)ethyl]imidazol-2-yl]ethyl]phenyl]-6-fluorobenzoic acid	1628045: Agonist activity at human BRS3 expressed in CHOK1 cells measured after 1 hrs by IP-One HTRF assay	ec50	0.0020	uM
N-methyl-1-[6-[4-(trifluoromethoxy)phenyl]sulfonyl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-7-yl]cyclobutane-1-carboxamide	660675: Displacement of 125I-dY-peptide from human BRS3 expressed in NFAT-CHO cells after 2 hrs by liquid scintillation counting	ic50	0.0021	uM
(2S)-3-(1H-indol-3-yl)-2-[[(2S)-2-[(2-phenylacetyl)amino]propanoyl]amino]-N-(2-phenylethyl)propanamide	42107: Effective concentration required against human bombesin receptor 3 (BRS-3) in CHO cells by using FLIPR assay.	ec50	0.0021	uM
3-(1H-indol-3-yl)-2-[[[2-(1H-indol-2-yl)acetyl]amino]carbamoylamino]-N-(2-phenylethyl)propanamide	42107: Effective concentration required against human bombesin receptor 3 (BRS-3) in CHO cells by using FLIPR assay.	ec50	0.0022	uM
6-(4-tert-butylphenyl)sulfonyl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-7-ol	704738: Displacement of [125I]-[D-Tyr6,beta-Ala11,Phe13,Nle14]-Bombesin(6-14) from human BRS3 expressed in CHO cells expressing NFAT after 2 hrs by liquid scintillation counting	ic50	0.0022	uM
[1-[5-(hydroxyamino)-1,4-dimethoxy-8-nitrosonaphthalen-2-yl]-2,2-dimethylbut-3-enyl] furan-2-carboxylate	1990905: Agonist activity at human BB3 stably overexpressed in human NCI-H1299 cells assessed as blockade of compound induced intracellular calcium response by measuring Bantag-1 pIC50 preincubated for 10 mins with Bantag-1 followed by compound addition and measured for 3 mins by FLIPR calcium 6 assay	ic50	0.0028	uM
2-[[2-[(4-chlorophenyl)methylamino]acetyl]amino]-3-(1H-indol-3-yl)-N-(2-phenylethyl)propanamide	42107: Effective concentration required against human bombesin receptor 3 (BRS-3) in CHO cells by using FLIPR assay.	ec50	0.0029	uM
2-[4-[2-[5-(2,2-dimethylpropyl)-1-(2-hydroxyethyl)imidazol-2-yl]ethyl]phenyl]-6-fluorobenzoic acid	1628045: Agonist activity at human BRS3 expressed in CHOK1 cells measured after 1 hrs by IP-One HTRF assay	ec50	0.0030	uM
4-[[5-(2,2-dimethylpropyl)-2-[2-[4-(3-fluoro-2-methoxycarbonylphenyl)phenyl]ethyl]imidazol-1-yl]methyl]benzoic acid	1628045: Agonist activity at human BRS3 expressed in CHOK1 cells measured after 1 hrs by IP-One HTRF assay	ec50	0.0030	uM
3-(1H-indol-3-yl)-2-[[(2-phenylacetyl)amino]carbamoylamino]-N-(2-phenylethyl)propanamide	42107: Effective concentration required against human bombesin receptor 3 (BRS-3) in CHO cells by using FLIPR assay.	ec50	0.0031	uM
6-(4-tert-butylphenyl)sulfonyl-7-chloro-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepine	704738: Displacement of [125I]-[D-Tyr6,beta-Ala11,Phe13,Nle14]-Bombesin(6-14) from human BRS3 expressed in CHO cells expressing NFAT after 2 hrs by liquid scintillation counting	ic50	0.0032	uM
7,8-dimethyl-6-[4-(trifluoromethoxy)phenyl]sulfonyl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepine	704738: Displacement of [125I]-[D-Tyr6,beta-Ala11,Phe13,Nle14]-Bombesin(6-14) from human BRS3 expressed in CHO cells expressing NFAT after 2 hrs by liquid scintillation counting	ic50	0.0033	uM
2-[(5R)-4-[2-[3-(cyclopropylmethoxycarbonyl)phenyl]acetyl]-8-(trifluoromethyl)-1,2,3,5-tetrahydropyrido[2,3-e][1,4]diazepin-5-yl]acetic acid	1176121: Agonist activity at human BRS3 expressed in CHO-K1 cells by IP-One HTRF assay	ec50	0.0034	uM
2-[3-(4-fluorophenoxy)phenyl]-1-[8-(trifluoromethyl)-1,2,3,5-tetrahydropyrido[2,3-e][1,4]diazepin-4-yl]ethanone	1069137: Agonist activity at human BRS-3 expressed in CHOK1 cells after 1 hr by HTRF assay	ec50	0.0036	uM
2-[(5R)-4-[2-(3-butoxycarbonylphenyl)acetyl]-8-(trifluoromethyl)-1,2,3,5-tetrahydropyrido[2,3-e][1,4]diazepin-5-yl]acetic acid	1176121: Agonist activity at human BRS3 expressed in CHO-K1 cells by IP-One HTRF assay	ec50	0.0040	uM
(2S)-2-[[(2S)-2-[(4-chlorophenyl)methylamino]propanoyl]amino]-3-(1H-indol-3-yl)-N-(2-phenylethyl)propanamide	42107: Effective concentration required against human bombesin receptor 3 (BRS-3) in CHO cells by using FLIPR assay.	ec50	0.0040	uM
2-[(5R)-4-[2-[3-(2-methylpropoxycarbonyl)phenyl]acetyl]-8-(trifluoromethyl)-1,2,3,5-tetrahydropyrido[2,3-e][1,4]diazepin-5-yl]acetic acid	1176121: Agonist activity at human BRS3 expressed in CHO-K1 cells by IP-One HTRF assay	ec50	0.0042	uM
6-(4-tert-butylphenyl)sulfonyl-7,8-dimethyl-5,11-dihydropyrido[3,2-c][1,5]benzodiazepine-2-carbonitrile	704738: Displacement of [125I]-[D-Tyr6,beta-Ala11,Phe13,Nle14]-Bombesin(6-14) from human BRS3 expressed in CHO cells expressing NFAT after 2 hrs by liquid scintillation counting	ic50	0.0044	uM
[1-[5-(hydroxyamino)-1,4-dimethoxy-8-nitrosonaphthalen-2-yl]-2,2-dimethylbut-3-enyl] benzoate	1990901: Agonist activity at human BB3 stably overexpressed in human NCI-H1299 cells assessed as increase in IP-1 accumulation incubated for 60 mins by HTRF assay	ec50	0.0048	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Ozone	increases reaction, increases expression, affects reaction, affects binding	2
bisphenol A	increases expression	1
sodium arsenite	increases expression	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Estradiol	increases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1

ChEMBL screening assays

70 unique, capped per target: 39 functional, 31 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1110001	Binding	Binding affinity to human BRS3	Synthesis and SAR of heterocyclic carboxylic acid isosteres based on 2-biarylethylimidazole as bombesin receptor subtype-3 (BRS-3) agonists for the treatment of obesity. — Bioorg Med Chem Lett
CHEMBL1110002	Functional	Agonist activity at human BRS3	Synthesis and SAR of heterocyclic carboxylic acid isosteres based on 2-biarylethylimidazole as bombesin receptor subtype-3 (BRS-3) agonists for the treatment of obesity. — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 3 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_H406	CHO-K1/BB3	Spontaneously immortalized cell line	Female
CVCL_KU51	CHO-K1 BRS3 Gq	Spontaneously immortalized cell line	Female
CVCL_KW44	PathHunter CHO-K1 BRS3 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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