CCKBR

Summary

CCKBR (cholecystokinin B receptor, HGNC:1571) is a protein-coding gene on chromosome 11p15.4, encoding Gastrin/cholecystokinin type B receptor (P32239). Receptor for the peptide hormones gastrin and cholecystokinin (CCK).

This gene encodes a G-protein coupled receptor for gastrin and cholecystokinin (CCK), regulatory peptides of the brain and gastrointestinal tract. This protein is a type B gastrin receptor, which has a high affinity for both sulfated and nonsulfated CCK analogs and is found principally in the central nervous system and the gastrointestinal tract. Alternative splicing results in multiple transcript variants. A misspliced transcript variant including an intron has been observed in cells from colorectal and pancreatic tumors.

Source: NCBI Gene 887 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 72 total — 1 pathogenic
• Druggable target: yes — 33 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_176875

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1571
Approved symbol	CCKBR
Name	cholecystokinin B receptor
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	CCK2R, GASR, CCK-BR, CCK-2R
Ensembl gene	ENSG00000110148
Ensembl biotype	protein_coding
OMIM	118445
Entrez	887

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000334619, ENST00000525014, ENST00000525462, ENST00000531712, ENST00000532396, ENST00000532715, ENST00000912313

RefSeq mRNA: 3 — MANE Select: NM_176875 NM_001318029, NM_001363552, NM_176875

CCDS: CCDS7761, CCDS81550, CCDS86175

Canonical transcript exons

ENST00000334619 — 5 exons

Exon	Start	End
ENSE00001101933	6270088	6270337
ENSE00001189179	6270646	6270803
ENSE00001189183	6259838	6260079
ENSE00001252585	6269669	6269920
ENSE00001332725	6271011	6272127

Expression profiles

Bgee: expression breadth ubiquitous, 148 present calls, max score 89.91.

FANTOM5 (CAGE): breadth broad, TPM avg 1.1614 / max 148.7107, expressed in 208 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112840	1.0843	204
112839	0.0770	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 10	UBERON:0013541	89.91	gold quality
frontal pole	UBERON:0002795	88.62	gold quality
prefrontal cortex	UBERON:0000451	87.26	gold quality
body of stomach	UBERON:0001161	87.05	gold quality
paraflocculus	UBERON:0005351	86.95	silver quality
right frontal lobe	UBERON:0002810	85.80	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	84.83	gold quality
cingulate cortex	UBERON:0003027	84.73	gold quality
middle temporal gyrus	UBERON:0002771	84.68	gold quality
anterior cingulate cortex	UBERON:0009835	84.66	gold quality
frontal cortex	UBERON:0001870	84.62	gold quality
Brodmann (1909) area 46	UBERON:0006483	84.31	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.30	gold quality
stomach	UBERON:0000945	84.28	gold quality
orbitofrontal cortex	UBERON:0004167	83.69	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.68	gold quality
neocortex	UBERON:0001950	83.67	gold quality
cerebellar cortex	UBERON:0002129	83.36	gold quality
cerebellar hemisphere	UBERON:0002245	83.34	gold quality
cerebellum	UBERON:0002037	82.63	gold quality
middle frontal gyrus	UBERON:0002702	82.61	gold quality
cerebellar vermis	UBERON:0004720	81.89	gold quality
endometrium epithelium	UBERON:0004811	81.29	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.78	gold quality
cerebral cortex	UBERON:0000956	80.70	gold quality
superior frontal gyrus	UBERON:0002661	79.19	gold quality
cardia of stomach	UBERON:0001162	78.78	gold quality
cortical plate	UBERON:0005343	77.49	gold quality
amygdala	UBERON:0001876	77.23	gold quality
temporal lobe	UBERON:0001871	77.14	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	1144.52
E-MTAB-10018	yes	457.70
E-ANND-3	yes	5.17

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, MYC, SP1

miRNA regulators (miRDB)

31 targeting CCKBR, 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-6867-5P	100.00	82.21	3464
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-6895-3P	98.79	65.69	996
HSA-MIR-5581-3P	98.55	70.31	1161
HSA-MIR-654-3P	98.38	67.61	905
HSA-MIR-6757-5P	98.08	65.50	724
HSA-MIR-5087	98.01	69.09	965
HSA-MIR-4257	97.86	68.05	1190
HSA-MIR-1914-5P	97.83	66.21	807
HSA-MIR-6791-3P	97.45	64.31	1123
HSA-MIR-6829-3P	97.45	64.31	1137
HSA-MIR-555	95.92	65.25	564
HSA-MIR-1178-5P	95.83	64.12	504

Literature-anchored findings (GeneRIF, showing 40)

• A misspliced form of the cholecystokinin-B/gastrin receptor in pancreatic carcinoma: role of reduced sellular U2AF35 and a suboptimal 3’-splicing site leading to retention of the fourth intron. (PMID:11830556)
• hGARE is proposed as a new candidate target gene in microsatellite instability tumorigenesis. (PMID:11896205)
• role in activating protein kinase D2 (PMID:12058027)
• Hyper-gastrinaemia may promote proliferation of human colonic adenomas that expressnon-truncated CCK-2 receptor isoforms. (PMID:12189558)
• data represent the first evidence for role in regulating cell-cell and cell-substrate adhesion and support a role in the progression of carcinoma (PMID:12400008)
• data support the hypothesis that cholecystokinin-B receptor mediated activation of the hypothalamic-pituitary-adrenal axis is relatively resistant to cortisol feedback inhibition (PMID:12510010)
• induction by oncogenic ras in LoVo and Colo320HSR colon cancer cell lines (PMID:12761477)
• Cholecystokinin-A receptor and B receptor polymorphisms, considered alone, showed no correlation with hallucinations in Parkinson’s disease (PMID:12777967)
• the presence of CCK receptors in human ductal pancreatic tumor samples is mainly due to CCK2 expression in residual pancreatic islets and CCK1 in pancreatic nerves. (PMID:12851875)
• this is the first report that provides evidence for the high tumorigenic effect of a constitutively active CCK2R mutant, thus raising a potential role of the CCK2R in human cancer. (PMID:12955087)
• heterodimerization of type A and B cholecystokinin receptors forms a powerful signaling unit with potential clinical significance in promoting cell growth (PMID:14534299)
• findings suggest physiological functions for the CCK(2)R in calcitonin-secretion and gene expression as well as a pathophysiological role in medullary thyroid carcinoma proliferation (PMID:14759564)
• CCK exerts secretagogue action on human ZG cells, acting through CCK2-Rs coupled to the adenylate cyclase/protein kinase A signaling cascade (PMID:15001623)
• A role is implicated for the CCKB receptor gene in suicide completers, the highest gene expression being observed in the cerebellum followed by cingulate gyrus and pre-frontal cortex compared to their age and sex-matched controls. (PMID:15036586)
• Gastrin/CCK-B receptor autocrine or paracrine pathway may possibly play an important role in the progression of gastric cancer. (PMID:15040018)
• CCK2i4svR, a splice variant of cholecystokinin-2 receptor, has a role in agonist-independent activation of Src tyrosine kinase (PMID:15292208)
• Findings are consistent with the notion that genetic variation in the CCK B receptor neurotransmitter system contributes to the pathogenesis of panic disorder. (PMID:15354400)
• the MEK1/ERK1/2 pathway couples the CCK2 receptor to nuclearization and DNA binding of Egr-1 (PMID:15611055)
• analysis of interspecies polymorphism in the human and rat cholecystokinin receptor-2 and its effect on the cholecystokinin binding site (PMID:15817487)
• Photoaffinity labeling of the type B CCK receptor provides evidence for the peptide-binding domain to include receptor loop and amino-terminal tail regions residing at the extracellular surface of the plasma membrane. (PMID:15850403)
• human normal, inflammatory, and malignant gastric tissues simultaneously express the classical and alternative splicing cholecystokinin-B/gastrin receptor genes (PMID:15989082)
• Study confirms that a high proportion of gastric cancer tissue samples express the gastrin/CCKB receptor, which can stimulate the growth of gastrin/CCKB receptor-positive gastric cancer cells. (PMID:16012719)
• CCK2 gastrin receptor may have a role in leukemia (PMID:16142371)
• Gastrin exerts an antiproliferative and proapoptotic effect on human colon cancer cells expressing the wild-type CCK2 receptor. (PMID:16143134)
• The expression rates of gastrin and gastrin receptor are high (about a half) in gastric carcinoma tissues, and there is an association between gastrin and gastrin receptor expression. (PMID:16228228)
• gastrin has pleiotropic effects in melanoma (PMID:16242076)
• Targeted CCK2R expression in the pancreas of Elas-CCK2 transgenic mice leads to the overexpression of beta 1-integrin. (PMID:16547500)
• Splice variant CCK(2i4sv) receptor may contribute to the growth and spread of gastrointestinal cancers through agonist-independent mechanisms that enhance tumor angiogenesis. (PMID:16909104)
• Mutational analysis of the key ITIM residue 438 confirmed that the CCK2R ITIM sequence is required for interaction with SHP-2 and the activation of the AKT pathway. (PMID:16963136)
• Data represent the evidence for the CCK2R regulating invasion and motility of colon cancer cells, and support a role of CCK2R in the progression of colon cancer. (PMID:16998832)
• It is suggested that CCK(2) receptors exert their modulating actions through a nitric oxide pathway, independent of the activity of the neuronal nitric oxide synthase isoform (PMID:17572695)
• A pathway comprising PKCs>Raf-1>MEK-1>ERK-1/-2 mediates the effect of gastrin on the CgA promoter, and strongly suggests that enhanced phosphorylation of Sp1 and CREB is crucial for CgA transactivation through the G protein-coupled CCK-B/gastrin receptor. (PMID:17889508)
• increased CCK2R expression might influence the outcome of epithelial inflammation and that the response may be mediated in part by myofibroblasts (PMID:17933865)
• Activation of splice variant of the CCK-2R retaining intron 4 by gastrin transactivates the COX-2 promoter in human colon cancer cells. (PMID:17936921)
• Signal transduction pathway is defined downstream of CCK2 receptor showing that CK1 delta and epsilon phosphorylate PKD2 at 3 sites, resulting in nuclear accumulation of PKD2 and phosphorylation of nuclear PKD2 substrates in human gastric cancer cells. (PMID:17962809)
• neuronal CCK may have a role in the regulation of the circadian rhythm, the metabolism of cerebral cholesterol and in the regulation of the plasminogen system (PMID:18028338)
• There was no significant correlation of expressin of gastrin, CCK-2 receptor, or gastrin precursosr with known histomorphological parameters in esophageal squamous cell carcinoma (PMID:18438722)
• Responses of human esophageal sphincter sling and clasp fibers to cholecystokinin (CCK) and gastrin through CCK-A and -B receptors are reported. (PMID:18444993)
• Results show that signaling through ACAT/cholesterol esterification is a novel pathway for the CCK2R that contributes to tumor cell proliferation and invasion. (PMID:19502590)
• The CCK(2)splice variant with retention of intron 4 (Ri4sv) is a marker of specific gastrointestinal and lung tumours. (PMID:19627395)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cckbra	ENSDARG00000074117
danio_rerio	cckbrb	ENSDARG00000076824
mus_musculus	Cckbr	ENSMUSG00000030898
rattus_norvegicus	Cckbr	ENSRNOG00000017679
drosophila_melanogaster	CCKLR-17D3	FBGN0030954
drosophila_melanogaster	CCKLR-17D1	FBGN0259231

Paralogs (16): NPFFR2 (ENSG00000056291), GNRHR (ENSG00000109163), HCRTR1 (ENSG00000121764), AVPR2 (ENSG00000126895), GALR3 (ENSG00000128310), HCRTR2 (ENSG00000137252), NPFFR1 (ENSG00000148734), CCKAR (ENSG00000163394), AVPR1A (ENSG00000166148), GALR1 (ENSG00000166573), GPR22 (ENSG00000172209), GPR150 (ENSG00000178015), OXTR (ENSG00000180914), FFAR4 (ENSG00000186188), QRFPR (ENSG00000186867), AVPR1B (ENSG00000198049)

Protein

Protein identifiers

Gastrin/cholecystokinin type B receptor — P32239 (reviewed: P32239)

Alternative names: Cholecystokinin-2 receptor

All UniProt accessions (3): P32239, E9PIC8, E9PJ49

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for the peptide hormones gastrin and cholecystokinin (CCK). Expressed throughout the central nervous system, where it modulates processes such as anxiety, analgesia, arousal and neuroleptic activity. Couples to both GNAI1 and GNAQ signaling pathways, but not to GNAS. Upon gastrin activation, reduces glucose absorption in intestinal epithelial cells by downregulating SGLT1 and GLUT2 expression through suppression of the PI3K/Akt/eIF4B pathway. In the kidney, decreases SGLT2 expression under high-glucose conditions via ERK/NF-kappa-B signaling. Isoform 2 is constitutively activated and may regulate cancer cell proliferation via a gastrin-independent mechanism.

Subunit / interactions. Interacts with GNAQ.

Subcellular location. Cell membrane.

Tissue specificity. Isoform 1 is expressed in brain, pancreas, stomach, the colon cancer cell line LoVo and the T-lymphoblastoma Jurkat, but not in heart, placenta, liver, lung, skeletal muscle, kidney or the stomach cancer cell line AGS. Expressed at high levels in the small cell lung cancer cell line NCI-H510, at lower levels in NCI-H345, NCI-H69 and GLC-28 cell lines, not expressed in GLC-19 cell line. Within the stomach, expressed at high levels in the mucosa of the gastric fundus and at low levels in the antrum and duodenum. Isoform 2 is present in pancreatic cancer cells and colorectal cancer cells, but not in normal pancreas or colonic mucosa. Isoform 3 is expressed in brain, pancreas, stomach, the stomach cancer cell line AGS and the colon cancer cell line LoVo.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P32239-1	1	yes
P32239-2	2, CCK-C, CCK-BRi4sv
P32239-3	3, DeltaCCK-B

RefSeq proteins (3): NP_001304958, NP_001350481, NP_795344* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000314	Gastrin_rcpt	Family
IPR009126	Cholcskin_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (52 total): helix 11, topological domain 8, sequence conflict 8, transmembrane region 7, sequence variant 5, glycosylation site 3, splice variant 2, strand 2, chain 1, region of interest 1, lipid moiety-binding region 1, disulfide bond 1, mutagenesis site 1, turn 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7F8W	ELECTRON MICROSCOPY	3.1
7XOW	ELECTRON MICROSCOPY	3.1
8IA7	ELECTRON MICROSCOPY	3.1
7F8V	ELECTRON MICROSCOPY	3.3
1L4T	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P32239-F1	76.56	0.46

Antibody-complex structures (SAbDab): 3 — 7F8W, 7XOW, 8IA7

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): 408

Disulfide bonds (1): 127–205

Glycosylation sites (3): 7, 30, 36

Mutagenesis-validated functional residues (1):

Position	Phenotype
324	three-fold increase of the coupling potency with gnas.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-416476	G alpha (q) signalling events
R-HSA-881907	Gastrin-CREB signalling pathway via PKC and MAPK

MSigDB gene sets: 141 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, RNGTGGGC_UNKNOWN, GOBP_DIGESTION, GOBP_ACID_SECRETION, MODULE_64, GOBP_DIGESTIVE_SYSTEM_DEVELOPMENT, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_SECRETION, GOBP_DIGESTIVE_SYSTEM_PROCESS, GOBP_REGULATION_OF_PH, GOMF_PEPTIDE_RECEPTOR_ACTIVITY, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOMF_G_PROTEIN_COUPLED_RECEPTOR_BINDING

GO Biological Process (12): gastric acid secretion (GO:0001696), cell surface receptor signaling pathway (GO:0007166), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of cytosolic calcium ion concentration (GO:0007204), neuropeptide signaling pathway (GO:0007218), positive regulation of cell population proliferation (GO:0008284), cholecystokinin signaling pathway (GO:0038188), pH reduction (GO:0045851), digestive tract development (GO:0048565), gland development (GO:0048732), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186)

GO Molecular Function (8): cholecystokinin receptor activity (GO:0004951), neuropeptide receptor activity (GO:0008188), gastrin receptor activity (GO:0015054), peptide hormone binding (GO:0017046), type B gastrin/cholecystokinin receptor binding (GO:0031741), 1-phosphatidylinositol-3-kinase regulator activity (GO:0046935), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

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

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1
G alpha (q) signalling events	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	4
G protein-coupled peptide receptor activity	3
signal transduction	2
digestive system process	1
acid secretion	1
phospholipase C activator activity	1
regulation of biological quality	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
regulation of pH	1
tube development	1
digestive system development	1
animal organ development	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
cholecystokinin signaling pathway	1
neuropeptide signaling pathway	1
neuropeptide binding	1
hormone binding	1
cholecystokinin receptor binding	1
1-phosphatidylinositol-3-kinase activity	1
kinase regulator activity	1
transmembrane signaling receptor activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1466 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCKBR	GAST	P01350	999
CCKBR	CCK	P06307	999
CCKBR	PTK7	Q13308	934
CCKBR	TCIRG1	Q13488	817
CCKBR	CCL28	Q9NRJ3	697
CCKBR	GNAQ	P50148	660
CCKBR	GIP	P09681	553
CCKBR	FGR	P09769	550
CCKBR	HCK	P08631	548
CCKBR	GCG	P01275	545
CCKBR	ATP4A	P20648	538
CCKBR	SRC	P12931	535
CCKBR	ATP12A	P54707	527
CCKBR	SST	P01166	524
CCKBR	HDC	P19113	512

IntAct

35 interactions, top by confidence:

A	B	Type	Score
CCKBR	PRKAG1	psi-mi:“MI:0914”(association)	0.640
PTPN11	CCKBR	psi-mi:“MI:0915”(physical association)	0.620
PTPN11	CCKBR	psi-mi:“MI:0914”(association)	0.620
NTM	CCKBR	psi-mi:“MI:0915”(physical association)	0.560
CCKBR	ABL1	psi-mi:“MI:0915”(physical association)	0.400
FYN	CCKBR	psi-mi:“MI:0915”(physical association)	0.400
CCKBR	GRB2	psi-mi:“MI:0915”(physical association)	0.400
CCKBR	NCK1	psi-mi:“MI:0915”(physical association)	0.400
CCKBR	CCK	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	CCKBR	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	CCKBR	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	CCKBR	psi-mi:“MI:0915”(physical association)	0.400
CCKBR	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
CCKBR	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
CCKBR	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
PPP1R9B	CCKBR	psi-mi:“MI:0915”(physical association)	0.400
CCKBR	ADRB2	psi-mi:“MI:0915”(physical association)	0.370
CCKBR	CCR4	psi-mi:“MI:0915”(physical association)	0.370
CCKBR	DRD2	psi-mi:“MI:0915”(physical association)	0.370
ATP13A2	CCKBR	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (27): NTM (Two-hybrid), GMCL1 (Affinity Capture-MS), KIRREL (Affinity Capture-MS), PXK (Affinity Capture-MS), PRKAB1 (Affinity Capture-MS), PRKAA1 (Affinity Capture-MS), PRKAG1 (Affinity Capture-MS), THADA (Affinity Capture-MS), CCKBR (Reconstituted Complex), CCKBR (Reconstituted Complex), CCKBR (Reconstituted Complex), SLCO1B3 (Reconstituted Complex), CCKBR (Two-hybrid), CCKBR (Two-hybrid), CCKBR (Two-hybrid)

ESM2 similar proteins: A0A287A2K5, F1MV99, O08858, O43193, O77808, O97772, P28646, P30098, P30552, P30553, P30796, P30872, P30873, P30937, P30938, P31391, P32239, P32300, P32307, P32745, P33533, P35346, P35370, P35377, P41143, P41146, P46095, P46627, P47748, P48044, P49660, P51651, P56481, P58406, P79266, P79292, Q49LX5, Q5D0K2, Q6W5G4, Q6YNI2

Diamond homologs: A0A287A2K5, C8YUV0, O00155, O02836, O08786, O15973, O18935, O19012, O19014, O19025, O19032, O19054, O19091, O62729, O77408, O77700, O77721, O77830, O97665, O97772, P04761, P08482, P0C5I1, P11229, P12657, P17200, P18089, P19328, P22270, P25021, P30545, P30551, P30552, P30553, P30796, P32211, P32238, P32239, P32302, P46627

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
CCKBR	“up-regulates activity”	GNAS	binding
CCKBR	“up-regulates activity”	GNAL	binding
CCKBR	“up-regulates activity”	GNAI1	binding
CCKBR	“up-regulates activity”	GNAI3	binding
CCKBR	“up-regulates activity”	GNAO1	binding
CCKBR	“up-regulates activity”	GNAQ	binding
CCKBR	“up-regulates activity”	GNA14	binding
CCKBR	“up-regulates activity”	GNA15	binding
Sincalide	“up-regulates activity”	CCKBR	“chemical activation”
CCK	up-regulates	CCKBR	binding
GAST	up-regulates	CCKBR	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	66
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4070979	NM_176875.4(CCKBR):c.701T>G (p.Met234Arg)	Pathogenic

SpliceAI

778 predictions. Top by Δscore:

Variant	Effect	Δscore
11:6269665:CCAGA:C	acceptor_loss	1.0000
11:6269666:CAGAA:C	acceptor_loss	1.0000
11:6269667:A:AG	acceptor_gain	1.0000
11:6269668:G:GG	acceptor_gain	1.0000
11:6269668:GA:G	acceptor_gain	1.0000
11:6269668:GAA:G	acceptor_gain	1.0000
11:6269921:GTGG:G	donor_gain	1.0000
11:6270083:TTTA:T	acceptor_loss	1.0000
11:6270085:TA:T	acceptor_loss	1.0000
11:6270086:A:AC	acceptor_loss	1.0000
11:6270086:A:AG	acceptor_gain	1.0000
11:6270086:AG:A	acceptor_gain	1.0000
11:6270086:AGG:A	acceptor_gain	1.0000
11:6270086:AGGG:A	acceptor_gain	1.0000
11:6270087:G:GA	acceptor_gain	1.0000
11:6270087:GG:G	acceptor_gain	1.0000
11:6270087:GGG:G	acceptor_gain	1.0000
11:6270087:GGGG:G	acceptor_gain	1.0000
11:6270087:GGGGT:G	acceptor_gain	1.0000
11:6271009:A:AG	acceptor_gain	1.0000
11:6271009:AGG:A	acceptor_gain	1.0000
11:6271009:AGGG:A	acceptor_gain	1.0000
11:6271010:G:GG	acceptor_gain	1.0000
11:6271010:GGG:G	acceptor_gain	1.0000
11:6271010:GGGG:G	acceptor_gain	1.0000
11:6260077:GAGGT:G	donor_loss	0.9900
11:6260080:G:GC	donor_loss	0.9900
11:6260081:T:G	donor_loss	0.9900
11:6269663:A:AG	acceptor_gain	0.9900
11:6269664:C:G	acceptor_gain	0.9900

AlphaMissense

2825 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:6269812:A:C	S99R	0.999
11:6269814:C:A	S99R	0.999
11:6269814:C:G	S99R	0.999
11:6270151:T:A	I156N	0.999
11:6269719:A:C	S68R	0.998
11:6269721:C:A	S68R	0.998
11:6269721:C:G	S68R	0.998
11:6269816:A:C	D100A	0.998
11:6269816:A:T	D100V	0.998
11:6269875:T:C	F120L	0.998
11:6269877:C:A	F120L	0.998
11:6269877:C:G	F120L	0.998
11:6269896:T:A	C127S	0.998
11:6269897:G:A	C127Y	0.998
11:6269897:G:C	C127S	0.998
11:6269898:C:G	C127W	0.998
11:6270099:A:C	S139R	0.998
11:6270101:T:A	S139R	0.998
11:6270101:T:G	S139R	0.998
11:6270114:A:C	S144R	0.998
11:6270116:C:A	S144R	0.998
11:6270116:C:G	S144R	0.998
11:6270151:T:C	I156T	0.998
11:6270219:T:A	W179R	0.998
11:6270219:T:C	W179R	0.998
11:6271242:C:G	P348R	0.998
11:6269733:T:A	N72K	0.997
11:6269733:T:G	N72K	0.997
11:6269816:A:G	D100G	0.997
11:6269896:T:C	C127R	0.997

dbSNP variants (sampled 300 via entrez): RS1000264793 (11:6268282 G>A), RS1000268929 (11:6268477 G>C), RS1000299868 (11:6268024 T>C), RS1000982349 (11:6263132 G>A), RS1001128125 (11:6270093 T>G), RS1001257899 (11:6269251 C>A,G,T), RS1001420981 (11:6262565 G>A), RS1001466417 (11:6262823 G>A), RS1001599920 (11:6267437 C>T), RS1001600628 (11:6262329 C>A), RS1002201887 (11:6263616 A>G), RS1002289716 (11:6270538 T>A,C), RS1003121235 (11:6259694 G>C,T), RS1003320063 (11:6259197 G>A), RS1003341449 (11:6258812 G>A)

Disease associations

OMIM: gene MIM:118445 | disease phenotypes: MIM:143890

GenCC curated gene-disease

Mondo (1): hypercholesterolemia, familial, 1 (MONDO:0007750)

Orphanet (1): Homozygous familial hypercholesterolemia (Orphanet:391665)

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST006630_25	Diastolic blood pressure	5.000000e-10
GCST008178_11	Early spontaneous preterm birth	2.000000e-06
GCST008832_5	Gastroesophageal reflux disease	2.000000e-08
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55
GCST012116_2	Rheumatic heart disease	3.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0006917	spontaneous preterm birth

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2095185 (PROTEIN FAMILY), CHEMBL298 (SINGLE PROTEIN), CHEMBL4523965 (SELECTIVITY GROUP)

Molecules with ChEMBL bioactivity

33 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 380,849 (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
CHEMBL1121	SINCALIDE	4	27,601
CHEMBL451	CHLORDIAZEPOXIDE	4	36,533
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL111	RIMONABANT	4	15,726
CHEMBL1201304	INDOCYANINE GREEN ACID FORM	4	7,044
CHEMBL1255800	FIDAXOMICIN	4	2,010
CHEMBL1328	PENTAGASTRIN	4	5,374
CHEMBL13280	FLUNITRAZEPAM	4	11,549
CHEMBL1401	NITAZOXANIDE	4	9,504
CHEMBL14376	ILOPERIDONE	4	7,878
CHEMBL1533	DESOGESTREL	4	9,566
CHEMBL1537	AZLOCILLIN	4	17,227
CHEMBL1617	RIFAXIMIN	4	13,380
CHEMBL1648	ISRADIPINE	4	20,026
CHEMBL2107430	FLUTRIMAZOLE	4	2,604
CHEMBL223228	EFAVIRENZ	4	35,999
CHEMBL3301612	ENCORAFENIB	4	4,624
CHEMBL41	FLUOXETINE	4	62,368
CHEMBL480	LANSOPRAZOLE	4	24,317
CHEMBL53	APOMORPHINE	4
CHEMBL83	TAMOXIFEN	4
CHEMBL92	DOCETAXEL ANHYDROUS	4
CHEMBL960	LEFLUNOMIDE	4
CHEMBL517427	NILVADIPINE	3
CHEMBL9506	DEVAZEPIDE	2
CHEMBL1269258	CE-326597	2
CHEMBL24938	LORGLUMIDE	2
CHEMBL283820	SPIROGLUMIDE	2
CHEMBL300072	PRANAZEPIDE	2

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2929183	CCKBR		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Cholecystokinin receptors

Most potent curated ligand interactions (48 total), top 25:

Ligand	Action	Affinity	Parameter
PD-149164	Antagonist	10.1	pIC50
[3H]PD140376	Antagonist	10.0	pKi
CCK-8	Full agonist	10.0	pIC50
PD-135666	Antagonist	9.8	pIC50
[3H]PBC-264	Full agonist	9.7	pKd
[125I]PD142308	Antagonist	9.6	pKd
YF-476	Antagonist	9.6	pKi
CCK-58	Full agonist	9.5	pIC50
BC-264	Full agonist	9.5	pIC50
[3H]JB-93182	Antagonist	9.5	pKd
GV150013	Antagonist	9.41	pIC50
Z-360	Antagonist	9.3	pKi
L-740093	Antagonist	9.2	pIC50
YM-022	Antagonist	9.2	pIC50
RB-400	Full agonist	9.1	pKi
PBC-264	Full agonist	9.1	pIC50
pentagastrin	Full agonist	9.1	pIC50
CI-988	Antagonist	9.1	pIC50
[125I]gastrin	Full agonist	9.0	pIC50
[3H]gastrin	Full agonist	9.0	pIC50
[125I]DTyr-Gly-[(Nle28,31)CCK-26-33	Full agonist	9.0	pIC50
PD-135158	Antagonist	8.9	pIC50
CCK-33	Full agonist	8.8	pIC50
desulfated cholecystokinin-8	Full agonist	8.7	pIC50
BBL-454	Full agonist	8.6	pKi

Binding affinities (BindingDB)

89 measured of 96 human assays (97 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(R)-3-[(R)-2-(Adamantan-2-yloxycarbonylamino)-3-(1H-indol-3-yl)-2-methyl-propionylamino]-4-(4-amino-phenyl)-butyric acid	KD	0.11 nM
(R)-3-[(R)-2-(Adamantan-2-yloxycarbonylamino)-3-(1H-indol-3-yl)-2-methyl-propionylamino]-4-(4-amino-3-iodo-phenyl)-butyric acid	KD	0.25 nM
CHEMBL118954	KI	0.661 nM
CHEMBL333517	KI	0.955 nM
(S)-2-((4R,5R)-2-Benzyl-4-methyl-1,3-dioxo-octahydro-pyrido[1,2-c]pyrimidin-5-ylamino)-3-(1H-indol-3-yl)-propionic acid adamantan-2-yl ester	IC50	0.96 nM
CHEMBL120363	KI	0.977 nM
CHEMBL333930	KI	1.3 nM
CHEMBL100548	KI	1.4 nM
CHEMBL118189	KI	1.4 nM
CHEMBL120031	KI	1.5 nM
3-{(R)-2-Amino-2-[(R)-2-(3-carboxy-propionylamino)-2-phenyl-ethylcarbamoyl]-propyl}-indole-1-carboxylic acid adamantan-2-yl ester	KI	1.7 nM
(3S)-3-[(2S)-2-[(2S)-2-{2-[(2S)-2-[(2S)-2-[(3S)-3-amino-3-formamidopropanoic acid]-3-[4-(sulfooxy)phenyl]propanamido]-4-(methylsulfanyl)butanamido]acetamido}-3-(1H-indol-3-yl)propanamido]-4-(methylsulfanyl)butanamido]-3-{[(1S)-1-carbamoyl-2-phenylethyl]carbamoyl}propanoic acid	KD	1.9 nM
CHEMBL331405	KI	1.9 nM
CHEMBL331688	KI	2.1 nM
CHEMBL329984	KI	2.3 nM
CHEMBL330977	KI	2.3 nM
CHEMBL120015	KI	2.3 nM
CHEMBL330409	KI	2.4 nM
CHEMBL119608	KI	3 nM
CHEMBL121028	KI	3.8 nM
PD-142251	KD	8.1 nM
CCK-A Agonist 20	KI	8.32 nM
(3S)-3-[(2S)-2-[(2S)-2-{2-[(2R)-2-[(2S)-2-amino-3-(4-hydroxyphenyl)propanamido]hexanamido]acetamido}-3-(1H-indol-3-yl)propanamido]hexanamido]-3-{[(1S)-1-carbamoyl-2-phenylethyl]carbamoyl}propanoic acid	KI	9.6 nM
CCK-A Agonist 15	KI	11 nM
CHEMBL120793	KI	11 nM
CHEMBL332128	KI	13 nM
CCK-A Agonist 23	KI	13.2 nM
CCK-A Agonist 21	KI	13.8 nM
(R)-1-[(R)-2-(Adamantan-2-yloxycarbonylamino)-3-(1H-indol-3-yl)-2-methyl-propionyl]-4-phenyl-pyrrolidine-2-carboxylic acid	KI	14 nM
CCK-A Agonist 24	KI	14.4 nM
CCK-A Agonist 43	KI	17 nM
CCK-A Agonist 22	KI	17.8 nM
CHEMBL390519	KI	19 nM
(2R,4S)-1-[(R)-2-(2-Aza-tricyclo[3.3.1.13,7]dec-2-yloxycarbonylamino)-3-(1H-indol-3-yl)-2-methyl-propionyl]-4-phenyl-pyrrolidine-2-carboxylic acid	KI	20 nM
CHEMBL432256	IC50	20 nM
(2R,4R)-1-[(R)-2-(2-Aza-tricyclo[3.3.1.13,7]dec-2-yloxycarbonylamino)-3-(1H-indol-3-yl)-2-methyl-propionyl]-4-benzyloxy-pyrrolidine-2-carboxylic acid	KI	24 nM
CCK-A Agonist 44	KI	25.1 nM
(2R,4R)-1-[(S)-2-(Adamantan-2-yloxycarbonylamino)-3-(1H-indol-3-yl)-2-methyl-propionyl]-4-phenoxy-pyrrolidine-2-carboxylic acid	KI	28 nM
CCK-A Agonist 33	KI	29.5 nM
(2R,4S)-1-[(R)-2-(2-Aza-tricyclo[3.3.1.13,7]dec-2-yloxycarbonylamino)-3-(1H-indol-3-yl)-2-methyl-propionyl]-4-(4-chloro-phenyl)-pyrrolidine-2-carboxylic acid	KI	32 nM
1-(4-{3-[4-(6-Fluoro-benzo[d]isoxazol-3-yl)-piperidin-1-yl]-propoxy}-3-methoxy-phenyl)-ethanone	KI	33 nM
CCK-A Agonist 27	KI	38.9 nM
CHEMBL318569	KI	43 nM
(2R,4R)-1-[(R)-2-(2-Aza-tricyclo[3.3.1.13,7]dec-2-yloxycarbonylamino)-3-(1H-indol-3-yl)-2-methyl-propionyl]-4-(3-chloro-benzyloxy)-pyrrolidine-2-carboxylic acid	KI	56 nM
CHEMBL121624	KI	60 nM
(2S,4S)-1-[(S)-2-(Adamantan-2-yloxycarbonylamino)-3-(1H-indol-3-yl)-2-methyl-propionyl]-4-phenoxy-pyrrolidine-2-carboxylic acid	KI	63 nM
CCK-A Agonist 18	KI	89.1 nM
(2R,4R)-1-[(R)-2-(Adamantan-2-yloxycarbonylamino)-3-(1H-indol-3-yl)-2-methyl-propionyl]-4-phenoxy-pyrrolidine-2-carboxylic acid	KI	91 nM
Tyr-D-Phe-Gly-Trp-Nle-Asp-Phe-NH2	KI	98 nM
(2R,4S)-1-[(S)-2-(Adamantan-2-yloxycarbonylamino)-3-(1H-indol-3-yl)-2-methyl-propionyl]-4-phenoxy-pyrrolidine-2-carboxylic acid	KI	98 nM

ChEMBL bioactivities

1962 potent at pChembl≥5 of 2195 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.68	Ki	0.021	nM	CHEMBL509524
10.39	Ki	0.0407	nM	CHEMBL452991
10.32	Ki	0.048	nM	CHEMBL509524
10.30	EC50	0.05012	nM	SINCALIDE
10.27	IC50	0.054	nM	CHEMBL2093059
10.22	Ki	0.06	nM	CHEMBL262894
10.13	IC50	0.074	nM	CHEMBL2110201
10.10	Ki	0.07943	nM	NETAZEPIDE
10.06	IC50	0.087	nM	CHEMBL49085
10.06	IC50	0.087	nM	CHEMBL432266
10.03	IC50	0.09333	nM	CHEMBL4563364
10.03	EC50	0.093	nM	SINCALIDE
10.00	EC50	0.1	nM	CHEMBL269016
10.00	IC50	0.1	nM	L-740093
10.00	IC50	0.1	nM	CHEMBL4282712
10.00	IC50	0.1	nM	CHEMBL431919
10.00	IC50	0.1	nM	CHEMBL545122
9.97	Ki	0.1072	nM	CHEMBL227276
9.96	Kd	0.11	nM	CHEMBL83942
9.96	IC50	0.11	nM	CHEMBL166941
9.92	IC50	0.12	nM	SINCALIDE
9.89	Ki	0.13	nM	CHEMBL2372781
9.88	IC50	0.1318	nM	CHEMBL4534236
9.88	IC50	0.1318	nM	CHEMBL4522865
9.86	IC50	0.138	nM	CI-988
9.86	Ki	0.138	nM	NETAZEPIDE
9.85	IC50	0.142	nM	CHEMBL349730
9.82	Ki	0.15	nM	CHEMBL428666
9.82	IC50	0.1514	nM	CHEMBL4561184
9.82	Ki	0.15	nM	CHEMBL411271
9.80	IC50	0.1585	nM	CHEMBL4468861
9.78	IC50	0.166	nM	CHEMBL4565336
9.75	Ki	0.1778	nM	CHEMBL415240
9.70	Ki	0.1995	nM	CHEMBL226583
9.70	IC50	0.2	nM	CHEMBL431919
9.70	IC50	0.2	nM	CHEMBL384035
9.70	IC50	0.2	nM	CHEMBL168263
9.68	Ki	0.2089	nM	CHEMBL333979
9.68	IC50	0.2089	nM	CHEMBL4443415
9.66	IC50	0.22	nM	CHEMBL137516
9.66	IC50	0.2188	nM	CHEMBL382409
9.66	Ki	0.22	nM	CHEMBL382409
9.66	IC50	0.22	nM	CHEMBL294161
9.65	Ki	0.2239	nM	CHEMBL331872
9.64	Ki	0.23	nM	CHEMBL384035
9.64	IC50	0.2291	nM	SINCALIDE
9.62	IC50	0.24	nM	CHEMBL412238
9.62	IC50	0.24	nM	CHEMBL137726
9.62	IC50	0.24	nM	CHEMBL75490
9.61	Ki	0.2455	nM	CHEMBL388144

PubChem BioAssay actives

1694 with measured affinity, of 3660 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-methyl-2-[2-[6-[[2-[2-[2-[3-[[(3R)-1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]carbamoylamino]phenoxy]ethylamino]-2-oxoethoxy]acetyl]amino]hexylamino]-2-oxoethoxy]acetamide	411818: Displacement of [125I]CCK-26-33 from CCK2 receptor expressed in CHO cells	ki	<0.0001	uM
2-[2-[4-[[2-[2-[[(4R,4aS,7S,7aR,12bS)-4a,10-dihydroxy-3-methyl-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]amino]-2-oxoethoxy]acetyl]amino]butylamino]-2-oxoethoxy]-N-methylacetamide	411824: Displacement of [3H]DAMGO from CCK2R-MOPR coexpressed in CHO cells	ki	<0.0001	uM
Sincalide	52405: Ability to stimulate intracellular calcium response was determined using CCK receptor-bearing chinese hamster ovary cell line	ec50	<0.0001	uM
1-[(3R)-1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]-3-[1-(2H-tetrazol-5-yl)-2,3-dihydroindol-6-yl]urea	50686: Inhibition of [125 I]BH CCK-8S binding to Cholecystokinin type B receptor in guinea pig cortical membranes	ic50	0.0001	uM
1-[(3R)-5-cyclohexyl-1-methyl-2-oxo-3H-1,4-benzodiazepin-3-yl]-3-[4-methyl-3-(2H-tetrazol-5-ylamino)phenyl]urea	50686: Inhibition of [125 I]BH CCK-8S binding to Cholecystokinin type B receptor in guinea pig cortical membranes	ic50	0.0001	uM
4-[[(1R)-2-[[(2R)-2-(2-adamantyloxycarbonylamino)-3-(1H-indol-3-yl)-2-methylpropanoyl]amino]-1-phenylethyl]amino]-4-oxobutanoic acid	51097: In vitro displacement of [125I]BH-CCK-8 from cDNA of human Cholecystokinin type B receptor expressed in CHO-K1 cells	ic50	0.0001	uM
1-[(3R)-5-(3-azabicyclo[3.2.2]nonan-3-yl)-1-methyl-2-oxo-3H-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea	50838: Inhibition of ligand binding to Cholecystokinin type B receptor from guinea pig cortical membrane.	ic50	0.0001	uM
2-[5-cyclohexyl-1-(2-cyclopentyl-2-oxoethyl)-2-oxo-1,3,4-benzotriazepin-3-yl]-N-[3-(5-oxo-4H-1,2,4-oxadiazol-3-yl)phenyl]acetamide	290976: Displacement of [3H]BH-CCK-8S from human recombinant CCK2 receptor expressed in NIH3T3 cells	ki	0.0001	uM
18-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-1-oxohexan-2-yl]amino]-1-oxo-3-(4-sulfooxyphenyl)propan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-2-oxoethoxy]ethoxy]ethylamino]-2-oxoethoxy]ethoxy]ethylamino]-1-carboxy-4-oxobutyl]amino]-18-oxooctadecanoic acid	1572002: Displacement of [125I]-CCK-8 from human CCK2R expressed in human 1321N1 cell membranes after 2 hrs by SPA assay	ic50	0.0001	uM
18-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-1-oxohexan-2-yl]amino]-1-oxo-3-(4-sulfooxyphenyl)propan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-2-oxoethoxy]ethoxy]ethylamino]-2-oxoethoxy]ethoxy]ethylamino]-1-carboxy-4-oxobutyl]amino]-18-oxooctadecanoic acid	1572002: Displacement of [125I]-CCK-8 from human CCK2R expressed in human 1321N1 cell membranes after 2 hrs by SPA assay	ic50	0.0001	uM
18-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-naphthalen-1-yl-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-1-oxohexan-2-yl]amino]-1-oxo-3-(4-sulfooxyphenyl)propan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-2-oxoethoxy]ethoxy]ethylamino]-2-oxoethoxy]ethoxy]ethylamino]-1-carboxy-4-oxobutyl]amino]-18-oxooctadecanoic acid	1572002: Displacement of [125I]-CCK-8 from human CCK2R expressed in human 1321N1 cell membranes after 2 hrs by SPA assay	ic50	0.0001	uM
1-[1-(3,3-dimethyl-2-oxobutyl)-2-oxo-5-pyridin-2-yl-3H-1,4-benzodiazepin-3-yl]-3-[3-(methylamino)phenyl]urea	1416315: Displacement of [125I]-gastrin17 from CCK-B receptor (unknown origin)	ic50	0.0001	uM
(3S)-4-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-[[(2S)-2-[[(2S)-3-(1H-indol-3-yl)-2-[[2-[[(2S)-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-(4-sulfooxyphenyl)propanoyl]amino]hexanoyl]amino]acetyl]amino]propanoyl]-methylamino]hexanoyl]amino]-4-oxobutanoic acid	50955: Binding affinity against cholecystokinin type B receptor on guinea pig cortex.	ki	0.0001	uM
1-[(3S)-1-(2-methylpropyl)-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]-3-[4-(2H-tetrazol-5-yl)phenyl]urea	50826: The compound was tested for binding activity against Cholecystokinin type B receptor from rat pancreatic tissue using [125]BH CCK-8 as radioligand	ic50	0.0001	uM
(3S)-4-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-[[(2S)-2-[[(2S)-3-(1H-indol-3-yl)-2-[[2-[[(2S)-2-[3-(4-sulfooxyphenyl)propanoylamino]hexanoyl]amino]acetyl]amino]propanoyl]amino]hexanoyl]-methylamino]-4-oxobutanoic acid	73663: Evaluated in vitro for maximal stimulatory activity for amylase release relative to CCK-8 in guinea pig tissue	ec50	0.0001	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-carboxypropanoyl]amino]hexanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]acetyl]amino]hexanoyl]amino]-3-(4-sulfophenyl)propanoyl]amino]butanedioic acid	50950: Displacement of [3H]pCCK-8 from cholecystokinin type B receptor in guinea pig brain membrane	ki	0.0001	uM
1-[(3R)-5-(3-azabicyclo[3.2.2]nonan-3-yl)-1-methyl-2-oxo-3H-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea;hydrochloride	50825: Binding activity against Cholecystokinin type B receptor from guinea pig cortex using [125]BH CCK-8s as radioligand.	ic50	0.0001	uM
1-[(3R)-1-(3,3-dimethyl-2-oxobutyl)-2-oxo-5-pyridin-2-yl-3H-1,4-benzodiazepin-3-yl]-3-[3-(methylamino)phenyl]urea	262760: Displacement of [125I]BH-CCK-8S from human recombinant CCK2 receptor expressed in NIH3T3 cells	ki	0.0001	uM
1-[(3R)-5-cyclohexyl-1-methyl-2-oxo-3H-1,4-benzodiazepin-3-yl]-3-[3-[methyl(2H-tetrazol-5-yl)amino]phenyl]urea	50686: Inhibition of [125 I]BH CCK-8S binding to Cholecystokinin type B receptor in guinea pig cortical membranes	ic50	0.0001	uM
1-[1-[2-(3-azabicyclo[3.2.2]nonan-3-yl)-2-oxoethyl]-5-(2-fluorophenyl)-2-oxo-3H-1,4-benzodiazepin-3-yl]-3-[3-(2H-tetrazol-5-yl)phenyl]urea	50678: Compound was evaluated for the inhibition of 124 I-CCK-8 binding at Cholecystokinin type B receptor on guinea pig cerebral cortical membranes	ic50	0.0001	uM
1-(3-methoxyphenyl)-3-[2-oxo-1-(2-oxo-2-pyrrolidin-1-ylethyl)-5-phenyl-3H-1,4-benzodiazepin-3-yl]urea	50816: Inhibition of binding of [125I]-CCK-8 to the cholecystokinin type B receptor	ic50	0.0002	uM
(3S)-4-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-[[(2S)-2-[[(2S)-3-(1H-indol-3-yl)-2-[[2-[[(2S)-2-[3-(4-sulfooxyphenyl)propanoylamino]hexanoyl]amino]acetyl]amino]propanoyl]-methylamino]-4-methylpentanoyl]amino]-4-oxobutanoic acid	50682: Evaluated in vitro for its binding affinity towards cholecystokinin type B receptor of guinea pig cortex	ic50	0.0002	uM
N,N-diethyl-2-[3-[(3-methoxyphenyl)carbamoylamino]-2-oxo-5-phenyl-3H-1,4-benzodiazepin-1-yl]acetamide	50816: Inhibition of binding of [125I]-CCK-8 to the cholecystokinin type B receptor	ic50	0.0002	uM
(3S)-3-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-1-[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-3-(1H-indol-3-yl)propanoyl]-methylamino]hexanoyl]amino]-4-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoic acid	1798047: Radioligand Labeled Binding Assay and Phosphatidylinositol Hydrolysis Assay for the CCK Receptor from Article 10.1021/jm050921q: “Structure-activity relationships of bifunctional peptides based on overlapping pharmacophores at opioid and cholecystokinin receptors.”	ki	0.0002	uM
1-[(3R)-5-cyclohexyl-1-methyl-2-oxo-3H-1,4-benzodiazepin-3-yl]-3-[3-(2H-tetrazol-5-ylamino)phenyl]urea	50686: Inhibition of [125 I]BH CCK-8S binding to Cholecystokinin type B receptor in guinea pig cortical membranes	ic50	0.0002	uM
2-[5-cyclohexyl-1-(3,3-dimethyl-2-oxobutyl)-2-oxo-1,3,4-benzotriazepin-3-yl]-N-[3-(5-oxo-4H-1,2,4-oxadiazol-3-yl)phenyl]acetamide	290976: Displacement of [3H]BH-CCK-8S from human recombinant CCK2 receptor expressed in NIH3T3 cells	ki	0.0002	uM
18-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-1-oxohexan-2-yl]amino]-1-oxo-3-(4-sulfooxyphenyl)propan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-2-oxoethoxy]ethoxy]ethylamino]-2-oxoethoxy]ethoxy]ethylamino]-1-carboxy-4-oxobutyl]amino]-18-oxooctadecanoic acid	1572002: Displacement of [125I]-CCK-8 from human CCK2R expressed in human 1321N1 cell membranes after 2 hrs by SPA assay	ic50	0.0002	uM
18-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxo-3-(4-sulfooxyphenyl)propan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-2-oxoethoxy]ethoxy]ethylamino]-2-oxoethoxy]ethoxy]ethylamino]-1-carboxy-4-oxobutyl]amino]-18-oxooctadecanoic acid	1572002: Displacement of [125I]-CCK-8 from human CCK2R expressed in human 1321N1 cell membranes after 2 hrs by SPA assay	ic50	0.0002	uM
18-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-(4-sulfooxyphenyl)propan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-2-oxoethoxy]ethoxy]ethylamino]-2-oxoethoxy]ethoxy]ethylamino]-1-carboxy-4-oxobutyl]amino]-18-oxooctadecanoic acid	1572002: Displacement of [125I]-CCK-8 from human CCK2R expressed in human 1321N1 cell membranes after 2 hrs by SPA assay	ic50	0.0002	uM
18-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxo-3-(4-sulfooxyphenyl)propan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-2-oxoethoxy]ethoxy]ethylamino]-2-oxoethoxy]ethoxy]ethylamino]-1-carboxy-4-oxobutyl]amino]-18-oxooctadecanoic acid	1572002: Displacement of [125I]-CCK-8 from human CCK2R expressed in human 1321N1 cell membranes after 2 hrs by SPA assay	ic50	0.0002	uM
5-[3-[[2-[5-cyclohexyl-1-(3,3-dimethyl-2-oxobutyl)-2-oxo-1,3,4-benzotriazepin-3-yl]acetyl]amino]phenyl]furan-2-carboxylic acid	290976: Displacement of [3H]BH-CCK-8S from human recombinant CCK2 receptor expressed in NIH3T3 cells	ki	0.0002	uM
(3S)-4-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-[[(2S)-2-[[(2S)-3-(1H-indol-3-yl)-2-[[2-[[(2S)-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-(4-sulfooxyphenyl)propanoyl]amino]hexanoyl]amino]acetyl]amino]propanoyl]amino]hexanoyl]amino]-4-oxobutanoic acid	50946: Displacement of 0.2 nM [3H]pCCK-8 from guinea pig brain membranes	ki	0.0002	uM
1-[1-(2-cyclopentylethyl)-5-(2-fluorophenyl)-2,4-dioxo-1,5-benzodiazepin-3-yl]-3-[3-(5H-tetrazol-5-yl)phenyl]urea	50964: In vitro inhibition of binding of [3H]pCCK-8 against Cholecystokinin type B receptor of guinea pig cerebral cortex membranes	ki	0.0002	uM
1-[1-(1-adamantylmethyl)-2,4-dioxo-5-phenyl-1,5-benzodiazepin-3-yl]-3-[3-(hydroxymethyl)phenyl]urea	50964: In vitro inhibition of binding of [3H]pCCK-8 against Cholecystokinin type B receptor of guinea pig cerebral cortex membranes	ki	0.0002	uM
1-[3-(dimethylamino)phenyl]-3-[5-(2-fluorophenyl)-1-(3-methylbutyl)-2,4-dioxo-1,5-benzodiazepin-3-yl]urea	50964: In vitro inhibition of binding of [3H]pCCK-8 against Cholecystokinin type B receptor of guinea pig cerebral cortex membranes	ki	0.0002	uM
1-(4-chlorophenyl)-3-[2-oxo-1-(2-oxo-2-pyrrolidin-1-ylethyl)-5-phenyl-3H-1,4-benzodiazepin-3-yl]urea	50819: Displacement of [125 I] CCK-8 from Cholecystokinin type B receptor of guinea pig cerebral cortex	ic50	0.0003	uM
1-[3-(dimethylamino)phenyl]-3-[1-(3,3-dimethylbutyl)-2,4-dioxo-5-phenyl-1,5-benzodiazepin-3-yl]urea	50964: In vitro inhibition of binding of [3H]pCCK-8 against Cholecystokinin type B receptor of guinea pig cerebral cortex membranes	ki	0.0003	uM
1-[(3R)-5-cyclohexyl-1-methyl-2-oxo-3H-1,4-benzodiazepin-3-yl]-3-[4-methyl-3-[methyl(2H-tetrazol-5-yl)amino]phenyl]urea	50686: Inhibition of [125 I]BH CCK-8S binding to Cholecystokinin type B receptor in guinea pig cortical membranes	ic50	0.0003	uM
1-[(3R)-5-cyclohexyl-1-methyl-2-oxo-3H-1,4-benzodiazepin-3-yl]-3-[3-[(2H-tetrazol-5-ylamino)methyl]phenyl]urea	50686: Inhibition of [125 I]BH CCK-8S binding to Cholecystokinin type B receptor in guinea pig cortical membranes	ic50	0.0003	uM
1-[1-(1-adamantylmethyl)-2,4-dioxo-5-phenyl-1,5-benzodiazepin-3-yl]-3-(3-aminophenyl)urea	50964: In vitro inhibition of binding of [3H]pCCK-8 against Cholecystokinin type B receptor of guinea pig cerebral cortex membranes	ki	0.0003	uM
1-[5-(2-fluorophenyl)-1-(3-methylbutyl)-2,4-dioxo-1,5-benzodiazepin-3-yl]-3-(3-methylsulfanylphenyl)urea	50964: In vitro inhibition of binding of [3H]pCCK-8 against Cholecystokinin type B receptor of guinea pig cerebral cortex membranes	ki	0.0003	uM
1-[(3S)-1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]-3-[4-(5-oxo-4H-1,2,4-oxadiazol-3-yl)phenyl]urea	50826: The compound was tested for binding activity against Cholecystokinin type B receptor from rat pancreatic tissue using [125]BH CCK-8 as radioligand	ic50	0.0003	uM
18-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-1-oxohexan-2-yl]amino]-1-oxo-3-(4-phosphonooxyphenyl)propan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-2-oxoethoxy]ethoxy]ethylamino]-2-oxoethoxy]ethoxy]ethylamino]-1-carboxy-4-oxobutyl]amino]-18-oxooctadecanoic acid	1572004: Agonist activity at human CCK2R expressed in human 1321N1 cells assessed as IP1 accumulation after 1 hr by HTRF assay	ec50	0.0003	uM
18-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-methylamino]-3-carboxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-(4-sulfooxyphenyl)propan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-2-oxoethoxy]ethoxy]ethylamino]-2-oxoethoxy]ethoxy]ethylamino]-1-carboxy-4-oxobutyl]amino]-18-oxooctadecanoic acid	1572002: Displacement of [125I]-CCK-8 from human CCK2R expressed in human 1321N1 cell membranes after 2 hrs by SPA assay	ic50	0.0003	uM
18-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[3-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-oxopropyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-(4-sulfooxyphenyl)propan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-2-oxoethoxy]ethoxy]ethylamino]-2-oxoethoxy]ethoxy]ethylamino]-1-carboxy-4-oxobutyl]amino]-18-oxooctadecanoic acid	1572004: Agonist activity at human CCK2R expressed in human 1321N1 cells assessed as IP1 accumulation after 1 hr by HTRF assay	ec50	0.0003	uM
(3S)-4-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-methylamino]-3-[[(2S)-1-[(2S)-3-(1H-indol-3-yl)-2-[[2-[[(2S)-2-[3-(4-sulfooxyphenyl)propanoylamino]hexanoyl]amino]acetyl]amino]propanoyl]-3-propylpyrrolidine-2-carbonyl]amino]-4-oxobutanoic acid	50664: Evaluated in vitro for its binding affinity towards cholecystokinin type B receptor of guinea pig cortex	ic50	0.0003	uM
(3S)-4-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-methylamino]-3-[[(2S)-2-[[(2S)-3-(1H-indol-3-yl)-2-[[2-[[(2S)-2-[3-(4-sulfooxyphenyl)propanoylamino]hexanoyl]amino]acetyl]amino]propanoyl]amino]hexanoyl]amino]-4-oxobutanoic acid	73663: Evaluated in vitro for maximal stimulatory activity for amylase release relative to CCK-8 in guinea pig tissue	ec50	0.0003	uM
2-[3-[[2-[5-cyclohexyl-1-(2-cyclopentyl-2-oxoethyl)-2-oxo-1,3,4-benzotriazepin-3-yl]acetyl]amino]phenyl]acetic acid	290976: Displacement of [3H]BH-CCK-8S from human recombinant CCK2 receptor expressed in NIH3T3 cells	ki	0.0003	uM
2-[6-[[2-[5-cyclohexyl-1-(3,3-dimethyl-2-oxobutyl)-2-oxo-1,3,4-benzotriazepin-3-yl]acetyl]amino]indol-1-yl]acetic acid	290976: Displacement of [3H]BH-CCK-8S from human recombinant CCK2 receptor expressed in NIH3T3 cells	ki	0.0003	uM
3-[3-[[2-[5-cyclohexyl-1-(2-cyclopentyl-2-oxoethyl)-2-oxo-1,3,4-benzotriazepin-3-yl]acetyl]amino]phenyl]propanoic acid	290976: Displacement of [3H]BH-CCK-8S from human recombinant CCK2 receptor expressed in NIH3T3 cells	ki	0.0003	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, increases expression, affects cotreatment	6
trichostatin A	affects cotreatment, decreases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
belinostat	decreases expression, affects cotreatment	2
Vorinostat	affects cotreatment, decreases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
bisphenol A	increases expression, affects reaction	1
gastrin 17	affects cotreatment, decreases expression, increases expression	1
cobaltous chloride	increases expression, increases reaction	1
butyraldehyde	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
pentanal	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Cocaine	decreases expression	1
Cytarabine	decreases expression	1
Estradiol	affects reaction, increases expression	1
Lead	affects expression	1
Methapyrilene	decreases methylation	1
Omeprazole	affects cotreatment, increases expression	1
Oxygen	increases expression, increases reaction	1
Polychlorinated Biphenyls	affects expression	1
Thiram	increases expression	1
Uranium Compounds	increases expression	1
Endocannabinoids	affects binding, decreases reaction, increases activity	1

ChEMBL screening assays

374 unique, capped per target: 322 binding, 51 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL653016	Functional	In vitro smooth muscle contraction activity in guinea pig ileum consists of two or three CCK receptor subtypes	N-methylated analogs of Ac[Nle28,31]CCK(26-33): synthesis, activity, and receptor selectivity. — J Med Chem
CHEMBL658779	Binding	Ability of compound to Inhibit the binding of [125I]BH-CCK-8 to Cholecystokinin receptor in isolated guinea pig brain membranes	Synthesis and biological activity of some partially modified retro-inverso analogues of cholecystokinin. — J Med Chem
CHEMBL5146166	Toxicity	Agonist activity at human CCK2R expressed in HEK293 cells assessed as ERK1/2 phosphorylation incubated for 5 mins by AlphaScreen assay	Peptide-based long-acting co-agonists of GLP-1 and cholecystokinin 1 receptors as novel anti-diabesity agents. — Eur J Med Chem

Cellosaurus cell lines

10 cell lines: 4 transformed cell line, 4 cancer cell line, 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9B9	Ubigene HEK293 CCKBR KO	Transformed cell line	Female
CVCL_H412	CHO-K1/CCKB	Spontaneously immortalized cell line	Female
CVCL_KB27	GeneBLAzer CCKBR-NFAT-bla HEK 293T	Transformed cell line	Female
CVCL_KW54	PathHunter CHO-K1 CCKBR beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KZ89	PathHunter U2OS CCKBR Activated GPCR Internalization	Cancer cell line	Female
CVCL_SH27	HAP1 CCKBR (-) 1	Cancer cell line	Male
CVCL_SH28	HAP1 CCKBR (-) 2	Cancer cell line	Male
CVCL_YK05	HEK293 CCKBR arrestin-Nomad	Transformed cell line	Female
CVCL_YK06	HEK293 CCKBR calcium-Nomad	Transformed cell line	Female
CVCL_YK36	U2OS CCKBR HiTSeeker	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06231459	PHASE4	COMPLETED	Expression of Pro- and Anti-inflammatory Cytokines During Anti-PCSK9 in Familial Hypercholesterolemia
NCT00000594	PHASE3	COMPLETED	NHLBI Type II Coronary Intervention Study
NCT00092833	PHASE3	TERMINATED	Investigational Drug in Patients With Hypercholesterolemia or in Patients With Sitosterolemia (0653-026)(COMPLETED)
NCT00134485	PHASE3	COMPLETED	Study To Evaluate The Safety And Efficacy Of Torcetrapib/Atorvastatin In Subjects With Familial Hypercholerolemia
NCT00134511	PHASE3	COMPLETED	Study To Evaluate The Effect Of Torcetrapib/Atorvastatin In Patients With Genetic High Cholesterol Disorder
NCT00136981	PHASE3	COMPLETED	Carotid B-Mode Ultrasound Study to Compare Anti-Atherosclerotic Effect of Torcetrpib/Atorvastatin to Atorvastatin Alone.
NCT00384293	PHASE3	TERMINATED	Carotid IMT (Intima Media Thickening) Study (0524A-041)(TERMINATED)
NCT01524289	PHASE3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT00280995	PHASE2	COMPLETED	Dose-escalating Safety Study of ISIS 301012 in Homozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT00281008	PHASE2	COMPLETED	Study of ISIS 301012 (Mipomersen) in Heterozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT01375751	PHASE2	COMPLETED	Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study
NCT00515307	PHASE1	COMPLETED	Bone Marrow Stem Cells as a Source of Allogenic Hepatocyte Transplantation in Homozygous Familial Hypercholesterolemia
NCT01583647	PHASE1	TERMINATED	A Study of Extended-release (ER) Niacin/Laropiprant in Adolescents With Heterozygous Familial Hypercholesterolemia (MK-0524A-158)
NCT00005168	Not specified	COMPLETED	Hyperapo B and Coronary Heart Disease
NCT01753232	Not specified	COMPLETED	Safety and Efficacy of the DALI LDL-adsorber and MONET Lipoprotein Filter
NCT03018678	Not specified	COMPLETED	Screening Protocol for a Gene Therapy Trial in Subjects With Homozygous Familial Hypercholesterolemia
NCT03110432	Not specified	COMPLETED	Prospective German Very High Cardiovascular Risk Patients Dyslipidemia Treatment Indication Registry
NCT03795038	Not specified	COMPLETED	Comparison of the Plasma Lipoprotein Apheresis Systems DIAMED and MONET vs. the Whole Blood Apheresis System DALI
NCT03989167	Not specified	RECRUITING	Clinical Decision Support for Familial Hypercholesterolemia
NCT04073797	Not specified	RECRUITING	PET Imaging of Inflammation and Lipid Lowering Study
NCT04118348	Not specified	COMPLETED	Evaluating the Efficacy of Pediatric Lipid Screening Alerts
NCT04313270	Not specified	UNKNOWN	Subclinical Atherosclerosis in Patients With Familial Hypercholesterolemia Treated With Evolocumab®
NCT04526457	Not specified	COMPLETED	Is Family Screening Improved by Genetic Testing of Familial Hypercholesterolemia
NCT04656028	Not specified	ACTIVE_NOT_RECRUITING	Genetic Testing and Motivational Counseling for FH
NCT04722068	Not specified	COMPLETED	Regeneron 1331 Kinetics Sub-Study HoFH
NCT04837638	Not specified	UNKNOWN	Diet Quality and Coronary Artery Calcification in Adults With Heterozygous Familial Hypercholesterolemia
NCT06555120	Not specified	RECRUITING	Screening for Familial Hypercholesterolemia in Children
NCT07543731	Not specified	NOT_YET_RECRUITING	A Real-World Study of Long-Term Adherence and Persistence to Inclisiran, Evolocumab, and Alirocumab