GRPR

Summary

GRPR (gastrin releasing peptide receptor, HGNC:4609) is a protein-coding gene on chromosome Xp22.2, encoding Gastrin-releasing peptide receptor (P30550). Receptor for gastrin-releasing peptide (GRP).

Gastrin-releasing peptide (GRP) regulates numerous functions of the gastrointestinal and central nervous systems, including release of gastrointestinal hormones, smooth muscle cell contraction, and epithelial cell proliferation and is a potent mitogen for neoplastic tissues. The effects of GRP are mediated through the gastrin-releasing peptide receptor. This receptor is a glycosylated, 7-transmembrane G-protein coupled receptor that activates the phospholipase C signaling pathway. The receptor is aberrantly expressed in numerous cancers such as those of the lung, colon, and prostate. An individual with autism and multiple exostoses was found to have a balanced translocation between chromosome 8 and a chromosome X breakpoint located within the gastrin-releasing peptide receptor gene.

Source: NCBI Gene 2925 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 83 total — 1 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005314

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4609
Approved symbol	GRPR
Name	gastrin releasing peptide receptor
Location	Xp22.2
Locus type	gene with protein product
Status	Approved
Aliases	BB2, BB2R, BRS2
Ensembl gene	ENSG00000126010
Ensembl biotype	protein_coding
OMIM	305670
Entrez	2925

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000380289

RefSeq mRNA: 1 — MANE Select: NM_005314 NM_005314

CCDS: CCDS14174

Canonical transcript exons

ENST00000380289 — 3 exons

Exon	Start	End
ENSE00000893445	16150305	16150656
ENSE00001484475	16152256	16153518
ENSE00001484478	16123565	16124366

Expression profiles

Bgee: expression breadth broad, 86 present calls, max score 83.05.

FANTOM5 (CAGE): breadth broad, TPM avg 1.6967 / max 164.9504, expressed in 254 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195627	1.3287	225
195628	0.2811	92
195626	0.0665	30
195629	0.0204	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.05	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.67	gold quality
buccal mucosa cell	CL:0002336	79.06	silver quality
body of pancreas	UBERON:0001150	78.22	gold quality
pancreatic ductal cell	CL:0002079	75.48	silver quality
triceps brachii	UBERON:0001509	73.17	gold quality
ileal mucosa	UBERON:0000331	73.01	silver quality
gluteal muscle	UBERON:0002000	73.00	gold quality
diaphragm	UBERON:0001103	70.59	gold quality
stromal cell of endometrium	CL:0002255	70.51	gold quality
pancreas	UBERON:0001264	69.30	gold quality
deltoid	UBERON:0001476	67.93	silver quality
olfactory bulb	UBERON:0002264	67.79	gold quality
type B pancreatic cell	CL:0000169	67.51	gold quality
quadriceps femoris	UBERON:0001377	67.36	gold quality
mammary duct	UBERON:0001765	67.12	gold quality
endometrium epithelium	UBERON:0004811	66.82	gold quality
vastus lateralis	UBERON:0001379	66.06	gold quality
epithelium of mammary gland	UBERON:0003244	65.67	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	65.20	gold quality
lower esophagus muscularis layer	UBERON:0035833	63.37	gold quality
lower esophagus	UBERON:0013473	63.08	gold quality
cranial nerve II	UBERON:0000941	62.05	silver quality
cerebellar vermis	UBERON:0004720	62.03	gold quality
colonic epithelium	UBERON:0000397	61.98	silver quality
tongue squamous epithelium	UBERON:0006919	61.71	gold quality
lower lobe of lung	UBERON:0008949	61.53	silver quality
CA1 field of hippocampus	UBERON:0003881	61.34	gold quality
vena cava	UBERON:0004087	61.17	gold quality
muscle tissue	UBERON:0002385	61.06	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-109979	no	175.93
E-ANND-3	no	2.82

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, ETS1, ZNF699

miRNA regulators (miRDB)

47 targeting GRPR, 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-574-5P	100.00	66.01	989
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891

Literature-anchored findings (GeneRIF, showing 40)

• GRP/GRP-R play a transient and non-critical role in intestinal development (PMID:11960700)
• hGRP-R activation stimulated sustained cyclic AMP response element binding protein (CREB) phosphorylation and transactivation in duodenal cancer cells through a protein kinase C and partially p38 mitogen-activated protein kinase-dependent pathway. (PMID:12220644)
• Bombesin-dependent activation (through GRP receptor) of the transcription factor Elk-1 and significant increase of cell proliferation in prostate cancer cell lines (PMID:12409226)
• mRNA transcripts are expressed in tumor cells of patients with small cell lung cancer (PMID:12474049)
• accumulation of mutations within the GRPR gene allows for the dedifferentiation of tumor cells within any particular colon cancer; poorly-differentiated tumor cells within any individual cancer may arise clonally from better-differentiated precursors (PMID:12720295)
• Increased gastrin-releasing peptide (GRP) receptor expression in small cell lung cancer cells confers sensitivity to [Arg6,D-Trp7,9,NmePhe8]-substance P (6-11)-induced growth inhibition (PMID:12771999)
• The expression of GRP-R in uterine tissue during specific phases of the cycle suggests a timely precise physiological action of GRP in these targets; in certain uterine neoplasms, the GRP-R overexpression may contribute to tumor development (PMID:15941862)
• Gastrin-releasing peptide receptor mediates activation of the epidermal growth factor receptor in lung cancer cells (PMID:15967120)
• GRP appears to rescue NSCLC cells exposed to gefitinib through release of amphiregulin and activation of the Akt pathway, suggesting GRPR and/or EGFR autocrine pathways in NSCLC cells may modulate therapeutic response to EGFR inhibitors. (PMID:17349623)
• The large amounts of GRP-receptors in ovarian tumor vessels suggest a role in tumoral vasculature and possibly angiogenesis. (PMID:17726264)
• There is a potential role of C6S and L181F mutations on GRPR function, and possibly in the pathogenesis of the autistic disorders. (PMID:18393381)
• genes encoding corticotropin releasing hormone receptor 1, tachykinin receptor 1, gastrin releasing peptide, and gastrin releasing peptide receptor were selected as candidates for PD based on their biology (PMID:18452185)
• CREB is a critical regulator of human GRP-R expression in gastrointestinal cancer and might be activated through different upstream intracellular pathways (PMID:18483184)
• Widespread GRPR expression in human cervical cancer. (PMID:18497507)
• These findings demonstrate that GRP and GRP-R have important oncogenic properties beyond their established mitogenic functions. (PMID:18753628)
• Gastrin-releasing peptide receptor is expressed in the vast majority of lymph node metastases and in 52.9% of bone metastases of prostate cancer. (PMID:19343734)
• High expression of gastrin-releasing peptide receptors is associated with the vascular bed of urinary tract cancers. (PMID:19478282)
• In MDA-MB-231 breast cancer cells, GRP-R and EGF-R synergize to regulate cell migration and IL-8 expression, but not cell proliferation. (PMID:19631337)
• The results suggest that brain-derived neurotrophic factor/TrkB and cAMP phosphodiesterase-4, but not the gastrin-releasing peptide receptor, regulate the viability of medulloblastoma cells. (PMID:19642024)
• This study is the first to confirm the presence of gastrin-releasing peptide receptor in human glioma specimens and normal human neurons. (PMID:20211708)
• GRP promotes the growth of HepG2 cells through interaction with GRPR co-expressed in tumor cells, and subsequently activates MAPK/ERK1/2 via EGFR-independent mechanisms. (PMID:20596631)
• Concomitant vascular GRP-receptor and VEGF-receptor expression in human tumors provides molecular basis for dual targeting of tumoral vasculature. (PMID:21605611)
• High GRPR is associated with prostate carcinoma. (PMID:22248281)
• Bronchial gastrin-releasing peptide receptor expression was significantly associated with lung cancer in a multivariable logistic regression model adjusted for age, sex, smoking status and pulmonary function. Lung cancer risk was not modified by sex. (PMID:22296774)
• Tonic stretch of human myometrium increases contractility and stimulates the expression of a known smooth muscle stimulatory agonist, GRP. GRP receptor antagonists attenuate the effect of stretch. (PMID:22411014)
• Elevated buccal GRPR espression was significantly associated with squamous cell carcinoma of the head and neck. (PMID:22431275)
• These findings highlight the role of GRPR signaling in sepsis outcome. (PMID:22735756)
• Protein kinase C is critically responsible for rapid VEGF secretion by gastrin-releasing peptide receptor signaling in neuroblastoma cells (PMID:23155231)
• integrin ss1 subunit critically regulates GRP-R-mediated neuroblastoma cell migration and invasion (PMID:23889963)
• GRPR is highly expressed in epidermoid carcinoma of the anal canal, suggesting this receptor might have a role in anal carcinogenesis. (PMID:23958544)
• GRPR expression was more pronounced in an advanced-stage lung cancer (PMID:24377816)
• BBS caused a significant increase in Shh gene transcription and protein secretion that was dependent on BBS-induced GPCR/Galphaq-//Rho mediated activation of nuclear factor kappaB (NFkappaB), which can stimulate a NF-kappaB response element in the Shh gene promoter (PMID:24747971)
• No association of 16 GRP and 7 GRPR variants were found with agoraphobia with/without panic disorder. (PMID:24912045)
• a key mechanism for GRPR-regulated colon cancer cell migration through the Galpha13-PRG-RhoA-ROCK pathway. (PMID:24958816)
• GRP-R regulates glucose metabolism in neuroblastoma by modulating HIF-1alpha, PDK4 and PDP2. (PMID:25630799)
• GRP/GRP-R signaling activation contributes to castration-resistant prostate cancer progression (PMID:27542219)
• Expression of Gastrin-Releasing Peptide Receptor in Breast Cancer and Its Association with Pathologic, Biologic, and Clinical Parameters (PMID:28280221)
• Our results suggest that, similar to what happens in neutrophils, gastrin-releasing peptide is a migratory, rather than a proliferative, stimulus, for non-small cell lung carcinoma cells, indicating a putative role for gastrin-releasing peptide and gastrin-releasing peptide receptor in metastasis (PMID:28351312)
• Novel Gastrin-Releasing Peptide Receptor Targeted Near-Infrared Fluorescence Dye for Image-Guided Surgery of Prostate Cancer. (PMID:31025163)
• Microglia-neuron interactions promote chronic itch via the NLRP3-IL-1beta-GRPR axis. (PMID:36876522)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	grpr	ENSDARG00000056620
mus_musculus	Grpr	ENSMUSG00000031364
rattus_norvegicus	Grpr	ENSRNOG00000004124
drosophila_melanogaster	CCHa2-R	FBGN0033058
drosophila_melanogaster	CCHa1-R	FBGN0050106

Paralogs (15): NTSR1 (ENSG00000101188), BRS3 (ENSG00000102239), MLNR (ENSG00000102539), GHSR (ENSG00000121853), 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

Gastrin-releasing peptide receptor — P30550 (reviewed: P30550)

Alternative names: GRP-preferring bombesin receptor

All UniProt accessions (2): P30550, X5D7H2

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for gastrin-releasing peptide (GRP). Signals via association with G proteins that activate a phosphatidylinositol-calcium second messenger system, resulting in Akt phosphorylation. Contributes to the regulation of food intake. Contributes to the perception of prurient stimuli and transmission of itch signals in the spinal cord that promote scratching behavior, but does not play a role in the perception of pain. Contributes primarily to nonhistaminergic itch sensation. In one study, shown to act in the amygdala as part of an inhibitory network which inhibits memory specifically related to learned fear. In another study, shown to contribute to disinhibition of glutamatergic cells in the auditory cortex via signaling on vasoactive intestinal peptide-expressing cells which leads to enhanced auditory fear memories. Contributes to the induction of sighing through signaling in the pre-Botzinger complex, a cluster of several thousand neurons in the ventrolateral medulla responsible for inspiration during respiratory activity.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in pancreas. Also expressed in stomach, adrenal cortex and brain. In brain, expressed in cells throughout the cortex.

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

RefSeq proteins (1): NP_005305* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR001556	Bombsn_rcpt-like	Family
IPR001966	Gastrin_pep_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (38 total): helix 12, topological domain 8, transmembrane region 7, strand 5, chain 1, modified residue 1, lipid moiety-binding region 1, glycosylation site 1, disulfide bond 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7W41	X-RAY DIFFRACTION	2.95
7W3Z	ELECTRON MICROSCOPY	3
7W40	ELECTRON MICROSCOPY	3
8H0Q	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30550-F1	78.78	0.52

Antibody-complex structures (SAbDab): 3 — 7W3Z, 7W40, 8H0Q

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 (2): 350, 339

Disulfide bonds (1): 113–196

Glycosylation sites (1): 20

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-416476	G alpha (q) signalling events

MSigDB gene sets: 127 (showing top): GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, GOBP_COGNITION, GOBP_BEHAVIOR, MODULE_64, GOBP_POSITIVE_REGULATION_OF_BEHAVIOR, LHX3_01, CAGCTG_AP4_Q5, GOBP_MULTICELLULAR_ORGANISMAL_RESPONSE_TO_STRESS, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, CCANNAGRKGGC_UNKNOWN, GOBP_REGULATION_OF_BEHAVIOR, GOBP_FEAR_RESPONSE, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTRASPECIES_INTERACTION_BETWEEN_ORGANISMS, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION

GO Biological Process (12): G protein-coupled receptor signaling pathway (GO:0007186), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), learning or memory (GO:0007611), social behavior (GO:0035176), psychomotor behavior (GO:0036343), regulation of cell population proliferation (GO:0042127), response to external biotic stimulus (GO:0043207), motor behavior (GO:0061744), positive regulation of respiratory gaseous exchange (GO:1903942), positive regulation of behavioral fear response (GO:2000987), signal transduction (GO:0007165), neuropeptide signaling pathway (GO:0007218)

GO Molecular Function (4): neuropeptide receptor activity (GO:0008188), G protein-coupled peptide receptor activity (GO:0008528), neuropeptide binding (GO:0042923), G protein-coupled receptor activity (GO:0004930)

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

Reactome top-level categories

Rollup of top-2 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	3
behavior	3
G protein-coupled receptor activity	2
regulation of cellular process	2
signal transduction	1
phospholipase C activator activity	1
cognition	1
biological process involved in intraspecies interaction between organisms	1
motor behavior	1
cell population proliferation	1
response to external stimulus	1
response to biotic stimulus	1
respiratory gaseous exchange by respiratory system	1
regulation of respiratory gaseous exchange	1
positive regulation of multicellular organismal process	1
behavioral fear response	1
positive regulation of defense response	1
positive regulation of behavior	1
positive regulation of fear response	1
regulation of behavioral fear response	1
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
neuropeptide signaling pathway	1
G protein-coupled peptide receptor activity	1
neuropeptide binding	1
peptide receptor activity	1
peptide binding	1
transmembrane signaling receptor activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1040 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRPR	GRP	P07491	999
GRPR	NMB	P08949	897
GRPR	FOLH1	Q04609	819
GRPR	SST	P01166	734
GRPR	TAC1	P20366	720
GRPR	GLRA2	P23416	674
GRPR	NPPB	P16860	666
GRPR	GAST	P01350	664
GRPR	NTNG2	Q96CW9	661
GRPR	NTNG1	Q9Y2I2	659
GRPR	GPM6B	Q13491	651
GRPR	GNAQ	P50148	626
GRPR	OPRM1	P35372	617
GRPR	PROCA1	Q8NCQ7	615
GRPR	NR0B1	P51843	608

IntAct

6 interactions, top by confidence:

A	B	Type	Score
RAMP3	GRPR	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	GRPR	psi-mi:“MI:0915”(physical association)	0.400
GRPR	GPR89A	psi-mi:“MI:0914”(association)	0.350

BioGRID (99): F2R (Affinity Capture-MS), ACVR2B (Affinity Capture-MS), GJC1 (Affinity Capture-MS), CDC42BPB (Affinity Capture-MS), USP30 (Affinity Capture-MS), HCCS (Affinity Capture-MS), SLC6A8 (Affinity Capture-MS), ASPHD2 (Affinity Capture-MS), ARL8B (Affinity Capture-MS), RAB4A (Affinity Capture-MS), TAP1 (Affinity Capture-MS), MFSD5 (Affinity Capture-MS), FADS1 (Affinity Capture-MS), MTG1 (Affinity Capture-MS), CBWD3 (Affinity Capture-MS)

ESM2 similar proteins: A5A4K9, A5A4L1, B2ZI34, F1MV99, O08725, O08786, O42329, O43193, O62709, O97772, P11616, P21451, P21729, P24053, P25099, P26684, P28088, P28190, P28646, P30542, P30550, P30551, P30872, P30873, P32238, P33534, P34970, P34975, P35342, P41144, P41145, P47745, P47751, P48302, P52500, P60893, P60894, P60895, Q2KIP6, Q49LX5

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

12 interactions.

A	Effect	B	Mechanism
GRP	up-regulates	GRPR	binding
GRPR	up-regulates	GNAQ	binding
GRPR	up-regulates	PLA2G1B	binding
GRPR	“up-regulates activity”	GNAS	binding
GRPR	“up-regulates activity”	GNAL	binding
GRPR	“up-regulates activity”	GNAI1	binding
GRPR	“up-regulates activity”	GNAI3	binding
GRPR	“up-regulates activity”	GNAO1	binding
GRPR	“up-regulates activity”	GNAZ	binding
GRPR	“up-regulates activity”	GNAQ	binding
GRPR	“up-regulates activity”	GNA14	binding
Bombesin	“up-regulates activity”	GRPR	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	38
Likely benign	13
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
816245	GRCh37/hg19 Xp22.33-22.13(chrX:168546-17502124)x1	Pathogenic

SpliceAI

396 predictions. Top by Δscore:

Variant	Effect	Δscore
X:16150451:A:T	donor_gain	1.0000
X:16152254:AGATT:A	acceptor_gain	1.0000
X:16152255:GATTG:G	acceptor_gain	1.0000
X:16150302:TAG:T	acceptor_loss	0.9900
X:16150303:A:AG	acceptor_gain	0.9900
X:16150303:AG:A	acceptor_loss	0.9900
X:16150304:G:GG	acceptor_gain	0.9900
X:16150450:G:GT	donor_gain	0.9900
X:16150653:GCAG:G	donor_gain	0.9900
X:16150657:G:T	donor_loss	0.9900
X:16150658:T:G	donor_loss	0.9900
X:16152238:AT:A	acceptor_gain	0.9900
X:16152238:ATGT:A	acceptor_gain	0.9900
X:16152239:T:G	acceptor_gain	0.9900
X:16152239:T:TA	acceptor_gain	0.9900
X:16152241:T:TA	acceptor_gain	0.9900
X:16152254:A:AG	acceptor_gain	0.9900
X:16152255:G:GT	acceptor_gain	0.9900
X:16152255:GA:G	acceptor_gain	0.9900
X:16152255:GAT:G	acceptor_gain	0.9900
X:16152255:GATT:G	acceptor_gain	0.9900
X:16124364:CAGG:C	donor_loss	0.9800
X:16124365:AGG:A	donor_loss	0.9800
X:16124366:GGT:G	donor_loss	0.9800
X:16124367:GT:G	donor_loss	0.9800
X:16126171:G:GG	donor_gain	0.9800
X:16150304:GAT:G	acceptor_gain	0.9800
X:16124368:TAAG:T	donor_loss	0.9700
X:16149476:G:GT	donor_gain	0.9700
X:16152238:A:AG	acceptor_gain	0.9700

AlphaMissense

2544 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:16124127:C:A	N58K	0.999
X:16124127:C:G	N58K	0.999
X:16124194:A:C	S81R	0.999
X:16124196:T:A	S81R	0.999
X:16124196:T:G	S81R	0.999
X:16124210:A:C	D86A	0.999
X:16124210:A:G	D86G	0.999
X:16124210:A:T	D86V	0.999
X:16124290:T:A	C113S	0.999
X:16124291:G:C	C113S	0.999
X:16150384:T:A	W165R	0.999
X:16150384:T:C	W165R	0.999
X:16152307:T:C	F273L	0.999
X:16152309:C:A	F273L	0.999
X:16152309:C:G	F273L	0.999
X:16124113:G:C	G54R	0.998
X:16124206:G:A	G85R	0.998
X:16124206:G:C	G85R	0.998
X:16124207:G:A	G85E	0.998
X:16124209:G:C	D86H	0.998
X:16124211:C:A	D86E	0.998
X:16124211:C:G	D86E	0.998
X:16124269:T:A	W106R	0.998
X:16124269:T:C	W106R	0.998
X:16124271:G:C	W106C	0.998
X:16124271:G:T	W106C	0.998
X:16124326:G:A	G125R	0.998
X:16124326:G:C	G125R	0.998
X:16124345:T:C	L131P	0.998
X:16150305:A:C	R138S	0.998

dbSNP variants (sampled 300 via entrez): RS1000029339 (X:16137552 A>C,T), RS1000229914 (X:16143594 G>T), RS1000341758 (X:16122794 A>G), RS1000447252 (X:16131596 A>T), RS1000458644 (X:16131927 A>G), RS1000654747 (X:16149370 A>T), RS1000706342 (X:16142692 G>A), RS1000774134 (X:16129169 G>T), RS1000785535 (X:16129852 C>G), RS1000791669 (X:16136518 C>T), RS1000911385 (X:16135770 G>A,C), RS1001004283 (X:16148629 A>G), RS1001023136 (X:16151209 G>A), RS1001282427 (X:16144044 T>C), RS1001290576 (X:16143470 C>T)

Disease associations

OMIM: gene MIM:305670 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008481_11	Lung function (FEV1/FVC)	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4524010 (PROTEIN FAMILY), CHEMBL4959 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,304 (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
CHEMBL437027	BOMBESIN	1	3,304

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 (40 total), top 25:

Ligand	Action	Affinity	Parameter
[D-Phe6,β-Ala11,Phe13,Nle14]bombesin-(6-14)	Full agonist	10.32	pIC50
bombesin	Agonist	10.15	pIC50
gastrin-releasing peptide	Full agonist	9.96	pIC50
neuromedin C	Full agonist	9.85	pIC50
gastrin releasing peptide(14-27) (human)	Full agonist	9.77	pIC50
[D-Tyr6,β-Ala11,N-Me-Ala13,Nle14]bombesin-(6-14)	Agonist	9.5	pKi
[D-Phe6]bombesin(6-13)propylamide	Antagonist	9.41	pIC50
JMV641	Antagonist	9.34	pIC50
[125I][D-Tyr6]bombesin-(6-13)-methyl ester	Antagonist	9.28	pKd
litorin	Agonist	9.27	pIC50
(D-Ala11]bombesin	Full agonist	9.27	pIC50
[(3-Ph-Pr6), His7,D-Ala11,D-Pro13,ψ13-14),Phe14]bombesin-(6-14)	Antagonist	9.2	pIC50
[D-Phe6, Leu13, Cpa14,ψ13-14]bombesin-(6-14)	Antagonist	8.91	pIC50
JMV594	Antagonist	8.9	pIC50
[Leu14]bombesin	Agonist	8.88	pIC50
[D-Tpi6, Leu13 ψ(CH2NH)-Leu14]bombesin-(6-14)	Antagonist	8.88	pIC50
[Phe13]bombesin	Full agonist	8.74	pKi
Ac-GRP-(20-26)-methylester	Antagonist	8.7	pIC50
ranatensin	Full agonist	8.65	pIC50
BAY86-7548	Antagonist	8.6	pIC50
[125I][Tyr4]bombesin	Full agonist	8.2	pKd
[Leu14, ψ 13-14)]bombesin	Antagonist	8.11	pIC50
[D-Phe6, Stat13, Leu14]Bn(6-14)	Antagonist	8.1	pIC50
neuromedin B (1-30) (human)	Full agonist	7.82	pIC50
neuromedin B	Full agonist	7.52	pIC50

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
SR 147778	KI	1000 nM

ChEMBL bioactivities

221 potent at pChembl≥5 of 223 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.40	Ki	0.04	nM	CHEMBL413196
10.22	IC50	0.06	nM	Demobesin 3
10.22	EC50	0.06	nM	CHEMBL525577
10.10	IC50	0.08	nM	CHEMBL414307
9.82	Ki	0.15	nM	BOMBESIN
9.82	IC50	0.15	nM	CHEMBL2371724
9.59	EC50	0.258	nM	BOMBESIN
9.43	EC50	0.373	nM	CHEMBL272335
9.33	IC50	0.47	nM	Demobesin 3
9.30	Ki	0.5	nM	CHEMBL3401466
9.23	IC50	0.59	nM	CHEMBL2372319
9.22	IC50	0.6	nM	CHEMBL266079
9.22	IC50	0.6	nM	CHEMBL3401466
9.19	IC50	0.65	nM	CHEMBL414307
9.15	Ki	0.7	nM	CHEMBL314375
9.15	Ki	0.7	nM	CHEMBL269432
9.14	IC50	0.72	nM	UNIVERSAL LIGAND
9.07	IC50	0.85	nM	CHEMBL2371726
9.00	Ki	1	nM	CHEMBL405908
9.00	Ki	0.99	nM	CHEMBL525577
8.91	IC50	1.24	nM	CHEMBL525820
8.89	IC50	1.3	nM	CHEMBL266079
8.84	IC50	1.45	nM	CHEMBL2372320
8.82	IC50	1.5	nM	CHEMBL3953323
8.82	IC50	1.5	nM	CHEMBL3927340
8.72	IC50	1.9	nM	CHEMBL3907272
8.71	IC50	1.94	nM	CHEMBL2371724
8.70	IC50	2	nM	BOMBESIN
8.70	IC50	2	nM	CHEMBL3904512
8.66	IC50	2.2	nM	CHEMBL3967904
8.60	IC50	2.5	nM	CHEMBL3963362
8.60	IC50	2.5	nM	CHEMBL3927633
8.60	IC50	2.5	nM	CHEMBL3984233
8.52	IC50	3	nM	CHEMBL3954296
8.52	IC50	3	nM	CHEMBL3985283
8.50	IC50	3.14	nM	CHEMBL6102759
8.47	IC50	3.4	nM	CHEMBL3979188
8.46	IC50	3.5	nM	CHEMBL3950452
8.46	IC50	3.5	nM	CHEMBL3960359
8.43	Ki	3.7	nM	CHEMBL312926
8.42	IC50	3.8	nM	CHEMBL3902429
8.40	IC50	4	nM	CHEMBL3905562
8.40	IC50	4	nM	CHEMBL3924852
8.40	IC50	4	nM	CHEMBL3917368
8.40	IC50	4	nM	CHEMBL3948894
8.40	IC50	4	nM	CHEMBL3924581
8.40	IC50	4	nM	CHEMBL3967299
8.40	IC50	4	nM	CHEMBL3951222
8.35	IC50	4.5	nM	CHEMBL3978233
8.35	IC50	4.5	nM	CHEMBL3935535

PubChem BioAssay actives

53 with measured affinity, of 123 total; 43 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
(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[2-[[2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-1-[(2S)-2-amino-3-methylbutanoyl]pyrrolidine-2-carbonyl]amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]acetyl]amino]acetyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]hexanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-4-oxobutanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]acetyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-methylpentanoyl]amino]-4-methylsulfanylbutanoic acid	42630: In vitro binding affinity at Bombesin BB2 receptor in the presence of [125I]-[Tyr] bombesin.	ki	<0.0001	uM
(2S)-2-[[2-[2-[4-[3-(2-aminoethylamino)-2-[(2-aminoethylamino)methyl]propyl]anilino]-2-oxoethoxy]acetyl]amino]-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide	242679: Displacement of [125 I-Tyr4]BB from human gastrin releasing peptide receptor expressed in PC-3 cell membranes	ic50	0.0001	uM
(2S)-N-[(2S)-1-[[(2S)-1-[[2-[[(2S)-4-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]-2-[[(2S)-5-oxopyrrolidine-2-carbonyl]amino]pentanediamide	42630: In vitro binding affinity at Bombesin BB2 receptor in the presence of [125I]-[Tyr] bombesin.	ki	0.0001	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	348844: Agonist activity at recombinant gastrin releasing peptide receptor expressed in baculovirus-transduced HEK293 cells assessed as intracellular calcium mobilization by FLIPR assay	ec50	0.0001	uM
(2S)-N-[(2S)-1-[[(2S)-1-[[2-[[(2S)-4-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-5-methylsulfanyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-2-[[(2S)-1-[3-(2-aminoethylamino)-2-[(2-aminoethylamino)methyl]propanoyl]pyrrolidine-2-carbonyl]amino]pentanediamide	242679: Displacement of [125 I-Tyr4]BB from human gastrin releasing peptide receptor expressed in PC-3 cell membranes	ic50	0.0001	uM
(2S)-N-[(2S)-1-[[(2S)-1-[[2-[[(2S)-4-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxoheptan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-2-[[(2S)-1-[3-(2-aminoethylamino)-2-[(2-aminoethylamino)methyl]propanoyl]pyrrolidine-2-carbonyl]amino]pentanediamide	242679: Displacement of [125 I-Tyr4]BB from human gastrin releasing peptide receptor expressed in PC-3 cell membranes	ic50	0.0001	uM
(2S)-2-[8-(6-aminohexanoylamino)octanoylamino]-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide	322034: Displacement of 125I[Tyr4]-bombesin from GRPR expressed in human PC3 cells	ec50	0.0004	uM
[[1-[2-[[1-[2-[[(2R)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(3S,4S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-6-methyl-1-oxoheptan-4-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoethyl]piperidin-4-yl]amino]-2-oxoethyl]triazol-4-yl]methyl-dimethylazaniumyl]methyl-trifluoroboranuide	1193752: Displacement of [125I-Tyr4]bombesin from GRPR (unknown origin) expressed in human PC3 cells after 45 mins by gamma counting analysis	ki	0.0005	uM
(2S)-2-[[2-[2-[4-[3-(2-aminoethylamino)-2-[(2-aminoethylamino)methyl]propyl]anilino]-2-oxoethoxy]acetyl]amino]-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxohexan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide	242679: Displacement of [125 I-Tyr4]BB from human gastrin releasing peptide receptor expressed in PC-3 cell membranes	ic50	0.0006	uM
(2S)-2-[6-[[(2R)-2-[[2-[(2-aminoacetyl)amino]acetyl]amino]-3-sulfanylpropanoyl]amino]hexanoylamino]-N-[(2S)-1-[[(2S)-1-[[2-[[(2S)-4-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]pentanediamide	397036: Displacement of [125I-Tyr4]BN form BB2 receptor in human PC3 cells	ic50	0.0006	uM
(2S)-2-acetamido-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide	42630: In vitro binding affinity at Bombesin BB2 receptor in the presence of [125I]-[Tyr] bombesin.	ki	0.0007	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	242208: Inhibition of gastrin releasing peptide receptor expressed in human prostate cancer cells	ic50	0.0007	uM
(2S)-N-[(2S)-1-[[(2S)-1-[[2-[[(2S)-4-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-2-[[(2S)-5-oxopyrrolidine-2-carbonyl]amino]pentanediamide	242679: Displacement of [125 I-Tyr4]BB from human gastrin releasing peptide receptor expressed in PC-3 cell membranes	ic50	0.0008	uM
(2S)-3-(1H-indol-3-yl)-N-[[1-(5-methoxy-2-pyridinyl)cyclohexyl]methyl]-2-methyl-2-[(4-nitrophenyl)carbamoylamino]propanamide	42631: Antagonistic activity against cloned human Bombesin receptor bb2 labeled with [125I]- [Tyr] bombesin stably expressed in CHO cells; 0.66-1.3	ki	0.0010	uM
(2S)-N-[(2S)-1-[[(2S,3R)-1-[[2-[[(2S)-4-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]-2-[[(2S)-5-oxopyrrolidine-2-carbonyl]amino]pentanediamide	397036: Displacement of [125I-Tyr4]BN form BB2 receptor in human PC3 cells	ic50	0.0012	uM
(2S)-2-[6-[[(2R)-2-[[2-[(2-aminoacetyl)amino]acetyl]amino]-3-sulfanylpropanoyl]amino]hexanoylamino]-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide	397036: Displacement of [125I-Tyr4]BN form BB2 receptor in human PC3 cells	ic50	0.0014	uM
(2S)-3-(1H-indol-3-yl)-N-[[1-(4-methoxyphenyl)cyclohexyl]methyl]-2-methyl-2-[(4-nitrophenyl)carbamoylamino]propanamide	42630: In vitro binding affinity at Bombesin BB2 receptor in the presence of [125I]-[Tyr] bombesin.	ki	0.0037	uM
(2S)-N-[(2S)-1-[[(2S)-1-[[2-[[(2S)-4-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-6-[(4-fluorobenzoyl)amino]-1-oxohexan-2-yl]-2-[[(2S)-5-oxopyrrolidine-2-carbonyl]amino]pentanediamide	772828: Displacement of [125I]-Tyr4-bombesin from GRP receptor in human PC3 cells	ic50	0.0053	uM
(2S)-N-[[1-(4-ethoxyphenyl)cyclohexyl]methyl]-3-(1H-indol-3-yl)-2-methyl-2-[(4-nitrophenyl)carbamoylamino]propanamide	42630: In vitro binding affinity at Bombesin BB2 receptor in the presence of [125I]-[Tyr] bombesin.	ki	0.0058	uM
(2S)-3-(1H-indol-3-yl)-2-methyl-2-[(4-nitrophenyl)carbamoylamino]-N-[[1-(4-nitrophenyl)cyclohexyl]methyl]propanamide	42630: In vitro binding affinity at Bombesin BB2 receptor in the presence of [125I]-[Tyr] bombesin.	ki	0.0064	uM
(2R)-3-[[(2R)-1-[[5-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(3S,4S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-6-methyl-1-oxoheptan-4-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-oxopentyl]amino]-1-oxo-3-sulfopropan-2-yl]amino]-2-[[2-[4-[ditert-butyl(fluoro)silyl]phenyl]acetyl]amino]-3-oxopropane-1-sulfonic acid	772907: Displacement of [125I]-Tyr4-bombesin from GRP receptor in human PC3 cells after 1 hr by gamma-counting analysis	ic50	0.0083	uM
(2S)-N-[[1-[4-(dimethylamino)phenyl]cyclohexyl]methyl]-3-(1H-indol-3-yl)-2-methyl-2-[(4-nitrophenyl)carbamoylamino]propanamide	42630: In vitro binding affinity at Bombesin BB2 receptor in the presence of [125I]-[Tyr] bombesin.	ki	0.0090	uM
(2S)-3-(1H-indol-3-yl)-2-methyl-2-[(4-nitrophenyl)carbamoylamino]-N-[(1-pyridin-2-ylcyclohexyl)methyl]propanamide	42630: In vitro binding affinity at Bombesin BB2 receptor in the presence of [125I]-[Tyr] bombesin.	ki	0.0170	uM
2-[4-[2-[[(2S)-1-[2-[2-[2-[[(5S)-5-[[(2S)-1-[(2S)-4-amino-2-[[(2S,3S)-2-amino-3-methylpentanoyl]amino]-4-oxobutanoyl]pyrrolidine-2-carbonyl]amino]-6-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-6-oxohexyl]amino]-2-oxoethoxy]ethoxy]ethylamino]-6-[[2-[2-[2-[2-[2-[[2-[4-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]carbamoyl]anilino]-2-oxoethyl]amino]-2-oxoethoxy]ethoxy]ethylamino]-2-oxoethoxy]acetyl]amino]-1-oxohexan-2-yl]amino]-2-oxoethyl]-7,10-bis(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetic acid	721182: Displacement of [125I]-Tyr4-BBN from human GRPR overexpressed in human T47D cells	ic50	0.0180	uM
(2S)-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(3S,4S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-6-methyl-1-oxoheptan-4-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-2-[5-[[(2S)-5-(diaminomethylideneamino)-2-[[2-[4-[ditert-butyl(fluoro)silyl]phenyl]acetyl]amino]pentanoyl]amino]pentanoylamino]pentanediamide	772829: Binding affinity to GRP receptor (unknown origin)	ic50	0.0229	uM
(2S)-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(3S,4S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-6-methyl-1-oxoheptan-4-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-2-[5-[[(2S)-5-(diaminomethylideneamino)-2-[[4-[2-[4-[ditert-butyl(fluoro)silyl]phenyl]ethylamino]-2,3-dihydroxy-4-oxobutanoyl]amino]pentanoyl]amino]pentanoylamino]pentanediamide	772907: Displacement of [125I]-Tyr4-bombesin from GRP receptor in human PC3 cells after 1 hr by gamma-counting analysis	ic50	0.0230	uM
(2S)-N-[[1-(4-hydroxyphenyl)cyclohexyl]methyl]-3-(1H-indol-3-yl)-2-methyl-2-[(4-nitrophenyl)carbamoylamino]propanamide	42630: In vitro binding affinity at Bombesin BB2 receptor in the presence of [125I]-[Tyr] bombesin.	ki	0.0320	uM
(2S)-N-[[1-(3,4-dimethoxyphenyl)cyclohexyl]methyl]-3-(1H-indol-3-yl)-2-methyl-2-[(4-nitrophenyl)carbamoylamino]propanamide	42630: In vitro binding affinity at Bombesin BB2 receptor in the presence of [125I]-[Tyr] bombesin.	ki	0.0330	uM
(2S)-2-[[2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[2-[[2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-1-[(2S)-2-amino-3-methylbutanoyl]pyrrolidine-2-carbonyl]amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]acetyl]amino]acetyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]hexanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]butanediamide	73201: Effective concentration required against gastrin releasing peptide receptor (GRP-R) in CHO cells by using FLIPR assay	ec50	0.0340	uM
(2S)-3-(1H-indol-3-yl)-2-methyl-2-[(4-nitrophenyl)carbamoylamino]-N-[[1-(4-propan-2-ylphenyl)cyclohexyl]methyl]propanamide	42630: In vitro binding affinity at Bombesin BB2 receptor in the presence of [125I]-[Tyr] bombesin.	ki	0.0350	uM
(2S)-2-[(4-cyanophenyl)carbamoylamino]-3-(1H-indol-3-yl)-2-methyl-N-[(1-pyridin-2-ylcyclohexyl)methyl]propanamide	42630: In vitro binding affinity at Bombesin BB2 receptor in the presence of [125I]-[Tyr] bombesin.	ki	0.0370	uM
(2S)-2-[(2-aminoacetyl)amino]-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3R)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]butanediamide	73201: Effective concentration required against gastrin releasing peptide receptor (GRP-R) in CHO cells by using FLIPR assay	ec50	0.0410	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[3-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2R)-2-amino-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]propanoylamino]-3-methylbutanoyl]amino]-3-phenylpropanoyl]amino]hexanoic acid	73201: Effective concentration required against gastrin releasing peptide receptor (GRP-R) in CHO cells by using FLIPR assay	ec50	0.0840	uM
(2S)-2-[(3,4-dichlorophenyl)carbamoylamino]-3-(1H-indol-3-yl)-2-methyl-N-[(1-pyridin-2-ylcyclohexyl)methyl]propanamide	42630: In vitro binding affinity at Bombesin BB2 receptor in the presence of [125I]-[Tyr] bombesin.	ki	0.0850	uM
(2S)-3-(1H-indol-3-yl)-2-methyl-2-[(3-nitrophenyl)carbamoylamino]-N-[(1-pyridin-2-ylcyclohexyl)methyl]propanamide	42630: In vitro binding affinity at Bombesin BB2 receptor in the presence of [125I]-[Tyr] bombesin.	ki	0.0850	uM
(2S)-3-(1H-indol-3-yl)-2-methyl-2-[(4-nitrophenyl)carbamoylamino]-N-[(1-phenylcyclohexyl)methyl]propanamide	42630: In vitro binding affinity at Bombesin BB2 receptor in the presence of [125I]-[Tyr] bombesin.	ki	0.0890	uM
(2S)-3-(1H-indol-3-yl)-2-methyl-N-[(1-pyridin-2-ylcyclohexyl)methyl]-2-[[4-(trifluoromethyl)phenyl]carbamoylamino]propanamide	42630: In vitro binding affinity at Bombesin BB2 receptor in the presence of [125I]-[Tyr] bombesin.	ki	0.1240	uM
(2S)-2-[(4-chlorophenyl)carbamoylamino]-3-(1H-indol-3-yl)-2-methyl-N-[(1-pyridin-2-ylcyclohexyl)methyl]propanamide	42630: In vitro binding affinity at Bombesin BB2 receptor in the presence of [125I]-[Tyr] bombesin.	ki	0.1490	uM
(2S)-3-(1H-indol-3-yl)-2-methyl-2-[(4-propan-2-ylphenyl)carbamoylamino]-N-[(1-pyridin-2-ylcyclohexyl)methyl]propanamide	42630: In vitro binding affinity at Bombesin BB2 receptor in the presence of [125I]-[Tyr] bombesin.	ki	0.2730	uM
(2S)-3-(1H-indol-3-yl)-N-[[1-(2-methoxyphenyl)cyclohexyl]methyl]-2-methyl-2-[(4-nitrophenyl)carbamoylamino]propanamide	42630: In vitro binding affinity at Bombesin BB2 receptor in the presence of [125I]-[Tyr] bombesin.	ki	0.4040	uM
(2S)-3-(1H-indol-3-yl)-2-methyl-2-(phenylcarbamoylamino)-N-[(1-pyridin-2-ylcyclohexyl)methyl]propanamide	42630: In vitro binding affinity at Bombesin BB2 receptor in the presence of [125I]-[Tyr] bombesin.	ki	1.0960	uM
(2S)-3-(1H-indol-3-yl)-2-methyl-2-[(2-nitrophenyl)carbamoylamino]-N-[(1-pyridin-2-ylcyclohexyl)methyl]propanamide	42630: In vitro binding affinity at Bombesin BB2 receptor in the presence of [125I]-[Tyr] bombesin.	ki	1.2540	uM
2-[4-[2-[5-(2,2-dimethylbutyl)-1H-imidazol-2-yl]ethyl]phenyl]pyridine	476903: Displacement of [125I]D-Tyr6-betaAla11-Phe13-Nle14-bombesin from human GRP-R expressed in NFAT-CHO cells after 2 hrs by scintillation counting	ic50	6.4000	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation	2
methylmercuric chloride	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
sodium arsenite	affects methylation	1
bombesin, Tyr(4)-	affects binding, decreases reaction	1
bisindolylmaleimide	decreases reaction, increases phosphorylation	1
bombesin (7-14)	affects binding, decreases reaction	1
abrine	increases expression	1
2-(3-(1,3-dicarboxypropyl)ureido)pentanedioic acid	affects binding, decreases reaction	1
(+)-JQ1 compound	decreases expression	1
1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane	affects binding, decreases reaction	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Androgens	affects expression	1
Copper	affects binding, decreases reaction	1
Cytarabine	decreases expression	1
Dichloroacetic Acid	increases response to substance	1
Drugs, Chinese Herbal	decreases expression	1
Silicon Dioxide	decreases expression	1
Tetradecanoylphorbol Acetate	increases phosphorylation	1
Valerates	affects binding, decreases reaction	1
Valproic Acid	increases expression	1
Aminocaproic Acid	affects binding, decreases reaction	1
Aflatoxin B1	decreases methylation	1
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer	increases phosphorylation, decreases reaction	1

ChEMBL screening assays

44 unique, capped per target: 38 binding, 6 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4880123	Binding	BB (non-select) CEREP ligand profiling	Data for DCP probe A-079
CHEMBL5665247	Functional	Agonist activity at GRPR (unknown origin)	In silico design of novel probes for the atypical opioid receptor MRGPRX2. — Nat Chem Biol

Cellosaurus cell lines

8 cell lines: 5 cancer cell line, 2 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_DA12	Ace-1(huGRPr)	Cancer cell line	Male
CVCL_H405	CHO-K1/BB2	Spontaneously immortalized cell line	Female
CVCL_KZ57	PathHunter HEK 293 GRPR beta-arrestin	Transformed cell line	Female
CVCL_LA47	PathHunter U2OS GRPR Activated GPCR Internalization	Cancer cell line	Female
CVCL_LA48	PathHunter U2OS GRPR beta-arrestin	Cancer cell line	Female
CVCL_YK47	U2OS GRPR calcium-Nomad	Cancer cell line	Female
CVCL_YK48	U2OS GRPR HiTSeeker	Cancer cell line	Female
CVCL_ZK86	GeneBLAzer GRPR-NFAT-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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