SCTR

Summary

SCTR (secretin receptor, HGNC:10608) is a protein-coding gene on chromosome 2q14.2, encoding Secretin receptor (P47872). G protein-coupled receptor activated by secretin (SCT), which is involved in different processes such as regulation of the pH of the duodenal content, food intake and water homeostasis.

The protein encoded by this gene is a G protein-coupled receptor and belongs to the glucagon-VIP-secretin receptor family. It binds secretin which is the most potent regulator of pancreatic bicarbonate, electrolyte and volume secretion. Secretin and its receptor are suggested to be involved in pancreatic cancer and autism.

Source: NCBI Gene 6344 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 90 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002980

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10608
Approved symbol	SCTR
Name	secretin receptor
Location	2q14.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000080293
Ensembl biotype	protein_coding
OMIM	182098
Entrez	6344

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 2 retained_intron

ENST00000019103, ENST00000485440, ENST00000494326, ENST00000627145, ENST00000630739, ENST00000903273, ENST00000903274, ENST00000903275, ENST00000903276, ENST00000971073, ENST00000971074, ENST00000971075

RefSeq mRNA: 1 — MANE Select: NM_002980 NM_002980

CCDS: CCDS2127

Canonical transcript exons

ENST00000019103 — 13 exons

Exon	Start	End
ENSE00000774723	119465789	119465886
ENSE00000925752	119494428	119494548
ENSE00001020655	119478811	119478918
ENSE00001351223	119524155	119524483
ENSE00001835003	119439843	119440257
ENSE00003495612	119441558	119441599
ENSE00003528278	119446759	119446885
ENSE00003579131	119461847	119462000
ENSE00003602906	119453287	119453347
ENSE00003607031	119452010	119452079
ENSE00003630864	119464123	119464255
ENSE00003639963	119448689	119448780
ENSE00003672602	119473453	119473556

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 98.14.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	98.14	gold quality
metanephros cortex	UBERON:0010533	92.69	gold quality
pancreas	UBERON:0001264	92.65	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.21	gold quality
islet of Langerhans	UBERON:0000006	85.63	gold quality
duodenum	UBERON:0002114	81.98	gold quality
right lung	UBERON:0002167	79.41	gold quality
upper lobe of left lung	UBERON:0008952	77.46	gold quality
upper lobe of lung	UBERON:0008948	75.17	gold quality
body of stomach	UBERON:0001161	75.04	gold quality
adult mammalian kidney	UBERON:0000082	74.33	gold quality
gall bladder	UBERON:0002110	74.30	gold quality
right uterine tube	UBERON:0001302	74.02	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.12	gold quality
germinal epithelium of ovary	UBERON:0001304	72.58	gold quality
right lobe of liver	UBERON:0001114	72.52	gold quality
right lobe of thyroid gland	UBERON:0001119	71.96	gold quality
left lobe of thyroid gland	UBERON:0001120	71.74	gold quality
stomach	UBERON:0000945	71.56	gold quality
thyroid gland	UBERON:0002046	70.54	gold quality
small intestine	UBERON:0002108	70.38	gold quality
right ovary	UBERON:0002118	70.29	gold quality
small intestine Peyer’s patch	UBERON:0003454	69.75	gold quality
left ovary	UBERON:0002119	69.72	gold quality
fundus of stomach	UBERON:0001160	67.81	gold quality
endocervix	UBERON:0000458	66.02	gold quality
jejunal mucosa	UBERON:0000399	65.99	silver quality
ovary	UBERON:0000992	65.94	gold quality
mucosa of transverse colon	UBERON:0004991	65.45	gold quality
transverse colon	UBERON:0001157	65.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1, SP3

miRNA regulators (miRDB)

4 targeting SCTR, 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-767-5P	99.95	70.85	993
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-7154-3P	97.65	65.02	985

Literature-anchored findings (GeneRIF, showing 27)

• promoter methylation plays a role in the regulation of SR gene expression. (PMID:14645499)
• Secretin receptor transcripts are present in Purkinje cells and basket cells in the molecular cell layer of human cerebellum. (PMID:15706223)
• There is a marked reduction in SCTR binding in ductal neoplasia. (PMID:16192632)
• Secretin receptor oligomerization occurs through -GxxxG- motif-independent interactions of transmembrane segments during the maturation of nascent molecules. (PMID:16819820)
• The high receptor expression in cholangiocarcinomas may be used for in vivo secretin receptor-targeting of these tumors and for the differential diagnosis with hepatocellular carcinoma. (PMID:16935383)
• A novel abnormal spliceoform of the secretin receptor was identified in pancreatic and bile duct cancers and developed as a dual antibody sandwich enzyme-linked immunosorbent assay for measure in the circulation. (PMID:17678920)
• Secretin-receptor and secretin-receptor-variant expressions occur in all gastrinomas (PMID:17711922)
• secretin receptors are new markers for bronchopulmonary carcinoid tumors (PMID:18223557)
• Data show that Family B G-protein-coupled receptor oligomerization occurs, with many structurally related members, such as the secretin receptor,associating with each other. (PMID:18401761)
• These results suggest that the secretin receptor can exist only as a structurally-specific homo-dimer, without being present as higher-order oligomers. (PMID:18680717)
• Increasing expression of secretin receptor competes for receptor modifying protein 3 (RAMP3) association with calcitonin receptor-like receptor (CLR) to yield a functional adrenomedullin receptor. (PMID:19886671)
• results demonstrate that secretin and/or the modulation of SCTR expression might have potential as a therapeutic tool in the treatment of cholangiocarcinoma (PMID:19904746)
• binding and activity of a series of 11 truncated and lactam-constrained secretin(5-27) analogues at the prototypic member of this family, the secretin receptor (PMID:21851058)
• Results suggest that Secretin is a potent modulator of adipocyte functions, demonstrating overall a role in enhanced substrate cycling. (PMID:22565418)
• Data suggest that the interaction between secretin peptide residue H1 and secretin receptor residue W274 is most compatible with a hydrophobic interaction. (PMID:22964305)
• Taken together, we propose here that the down-regulatory effects of NRSF on hSCTR gene expression are mediated via its suppression on Sp1-mediated transactivation. (PMID:23168245)
• High SCTR expression is associated with liver metastases of pancreas neuroendocrine tumors. (PMID:25241033)
• Our findings indicate that SCTR suppresses the proliferation of normal breast cells, while the gene stimulates the proliferation and migration of cancer cells being downregulated by promoter methylation. (PMID:26397240)
• Cysteine trapping identified charge-charge interactions between secretin and secretin receptor residues in TM5, TM6, ECL2, and ECL3 domains. (PMID:26740626)
• elevated in primary sclerosing cholangitis liver samples compared to healthy controls (PMID:27115285)
• Structure and Function of Cross-class Complexes of G Protein-coupled Secretin and Angiotensin 1a Receptors. (PMID:27330080)
• High secretin/secretin receptor signaling mediates biliary damage and liver fibrosis in early-stage primary biliary cholangitis. (PMID:31251081)
• Structure and dynamics of the active Gs-coupled human secretin receptor. (PMID:32811827)
• SCTR hypermethylation is a diagnostic biomarker in colorectal cancer. (PMID:32970347)
• Structure of the human secretin receptor coupled to an engineered heterotrimeric G protein. (PMID:33008599)
• Inhibition of Secretin/Secretin Receptor Axis Ameliorates NAFLD Phenotypes. (PMID:33928675)
• Expression of Secretin and its Receptor Along the Intestinal Tract in Type 2 Diabetes Patients and Healthy Controls. (PMID:37335970)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sctr	ENSMUSG00000026387
rattus_norvegicus	Sctr	ENSRNOG00000049766

Paralogs (42): CALCR (ENSG00000004948), GIPR (ENSG00000010310), ADGRA2 (ENSG00000020181), CALCRL (ENSG00000064989), GLP2R (ENSG00000065325), ADGRF5 (ENSG00000069122), ADGRL1 (ENSG00000072071), ADCYAP1R1 (ENSG00000078549), VIPR2 (ENSG00000106018), CRHR2 (ENSG00000106113), GHRHR (ENSG00000106128), ADGRD1 (ENSG00000111452), GLP1R (ENSG00000112164), ADGRG6 (ENSG00000112414), VIPR1 (ENSG00000114812), ADGRL2 (ENSG00000117114), CRHR1 (ENSG00000120088), ADGRB2 (ENSG00000121753), ADGRE5 (ENSG00000123146), ADGRE2 (ENSG00000127507), ADGRE3 (ENSG00000131355), ADGRB3 (ENSG00000135298), PTH2R (ENSG00000144407), ADGRG7 (ENSG00000144820), ADGRL3 (ENSG00000150471), ADGRA3 (ENSG00000152990), ADGRF1 (ENSG00000153292), ADGRF4 (ENSG00000153294), ADGRG4 (ENSG00000156920), ADGRG5 (ENSG00000159618), PTH1R (ENSG00000160801), ADGRL4 (ENSG00000162618), EVA1C (ENSG00000166979), ADGRF3 (ENSG00000173567), ADGRG2 (ENSG00000173698), ADGRE1 (ENSG00000174837), ADGRD2 (ENSG00000180264), ADGRB1 (ENSG00000181790), ADGRG3 (ENSG00000182885), ADGRA1 (ENSG00000197177)

Protein

Protein identifiers

Secretin receptor — P47872 (reviewed: P47872)

All UniProt accessions (3): P47872, A0A0D9SFV7, A0A0D9SFY2

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor activated by secretin (SCT), which is involved in different processes such as regulation of the pH of the duodenal content, food intake and water homeostasis. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and activates cAMP-dependent pathway. Upon binding to secretin, regulates the pH of the duodenum by (1) inhibiting the secretion of gastric acid from the parietal cells of the stomach and (2) stimulating the production of bicarbonate (NaHCO(3)) from the ductal cells of the pancreas. In addition to regulating the pH of the duodenal content, plays a central role in diet induced thermogenesis: acts as a non-sympathetic brown fat (BAT) activator mediating prandial thermogenesis, which consequentially induces satiation. Mechanistically, secretin released by the gut after a meal binds to secretin receptor (SCTR) in brown adipocytes, activating brown fat thermogenesis by stimulating lipolysis, which is sensed in the brain and promotes satiation. Also able to stimulate lipolysis in white adipocytes. Also plays an important role in cellular osmoregulation by regulating renal water reabsorption. Also plays a role in the central nervous system: required for synaptic plasticity.

Subcellular location. Cell membrane. Basolateral cell membrane.

Post-translational modifications. Phosphorylated on Ser and Thr residues at the cytoplasmic C-terminus by G protein-coupled receptor kinases (GRKs).

Similarity. Belongs to the G-protein coupled receptor 2 family.

RefSeq proteins (1): NP_002971* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000832	GPCR_2_secretin-like	Family
IPR001879	GPCR_2_extracellular_dom	Domain
IPR002144	GPCR_2_secretin_rcpt	Family
IPR017981	GPCR_2-like_7TM	Domain
IPR017983	GPCR_2_secretin-like_CS	Conserved_site
IPR036445	GPCR_2_extracell_dom_sf	Homologous_superfamily
IPR047037	Secretin_7TM	Domain
IPR050332	GPCR_2	Family

Pfam: PF00002, PF02793

UniProt features (58 total): helix 14, topological domain 8, transmembrane region 7, turn 6, glycosylation site 5, sequence conflict 5, strand 5, disulfide bond 4, sequence variant 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6WZG	ELECTRON MICROSCOPY	2.3
7D3S	ELECTRON MICROSCOPY	2.9
6WI9	ELECTRON MICROSCOPY	4.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P47872-F1	77.18	0.31

Antibody-complex structures (SAbDab): 3 — 6WI9, 6WZG, 7D3S

Functional residue map

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

Disulfide bonds (4): 45–75, 66–107, 89–123, 215–285

Glycosylation sites (5): 72, 100, 106, 128, 291

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-418555	G alpha (s) signalling events
R-HSA-420092	Glucagon-type ligand receptors
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373080	Class B/2 (Secretin family receptors)
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 106 (showing top): MODULE_92, REACTOME_GLUCAGON_TYPE_LIGAND_RECEPTORS, BENPORATH_ES_WITH_H3K27ME3, GOBP_RESPONSE_TO_DIETARY_EXCESS, GOBP_CELL_CELL_SIGNALING, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_REGULATION_OF_SYNAPTIC_PLASTICITY, MODULE_289, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_REGULATION_OF_CELL_SIZE, GOBP_SYNAPTIC_SIGNALING, GOBP_REGULATION_OF_APPETITE, GOMF_PEPTIDE_RECEPTOR_ACTIVITY, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS

GO Biological Process (10): diet induced thermogenesis (GO:0002024), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), intracellular water homeostasis (GO:0009992), response to nutrient levels (GO:0031667), regulation of appetite (GO:0032098), regulation of synaptic plasticity (GO:0048167), signal transduction (GO:0007165)

GO Molecular Function (5): G protein-coupled peptide receptor activity (GO:0008528), secretin receptor activity (GO:0015055), peptide hormone binding (GO:0017046), transmembrane signaling receptor activity (GO:0004888), G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (4): cytoplasmic microtubule (GO:0005881), plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Signaling by GPCR	2
GPCR downstream signalling	1
Class B/2 (Secretin family receptors)	1
Signal Transduction	1
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor activity	3
signal transduction	2
G protein-coupled receptor signaling pathway	2
regulation of biological quality	2
response to dietary excess	1
adaptive thermogenesis	1
adenylate cyclase activity	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
cell volume homeostasis	1
intracellular chemical homeostasis	1
response to stimulus	1
response to nutrient levels	1
modulation of chemical synaptic transmission	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
peptide receptor activity	1
hormone binding	1
signaling receptor activity	1
transmembrane signaling receptor activity	1
cytoplasm	1
microtubule	1
membrane	1
cell periphery	1
basal plasma membrane	1
plasma membrane region	1
cellular anatomical structure	1

Protein interactions and networks

STRING

734 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCTR	SCT	P09683	998
SCTR	ANO6	Q4KMQ2	967
SCTR	VIP	P01282	935
SCTR	ADCYAP1	P18509	831
SCTR	ADGRA1	Q86SQ6	817
SCTR	PTH	P01270	770
SCTR	GCG	P01275	756
SCTR	AQP2	P41181	723
SCTR	BAIAP3	O94812	701
SCTR	GIP	P09681	613
SCTR	CFTR	P13569	606
SCTR	RAMP3	O60896	603
SCTR	PTHLH	P12272	597
SCTR	ADGRG1	Q9Y653	592
SCTR	SLC4A2	P04920	523

IntAct

4 interactions, top by confidence:

A	B	Type	Score
SCTR	CALM1	psi-mi:“MI:0915”(physical association)	0.400
SCTR	DNAL4	psi-mi:“MI:0915”(physical association)	0.370
CYFIP1	SCTR	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (8): SCT (Reconstituted Complex), ADCYAP1 (Protein-peptide), CPAMD8 (Protein-peptide), SCTR (Protein-peptide), SCTR (Protein-peptide), SCTR (Protein-peptide), SCTR (Two-hybrid), SCTR (Two-hybrid)

ESM2 similar proteins: A0A2Z2U4G9, O35659, O46502, O95838, P23811, P25107, P25117, P25961, P30082, P30083, P30988, P32082, P32214, P32215, P32241, P32301, P34999, P35000, P41587, P41588, P41593, P43218, P43219, P43220, P47871, P47872, P48546, P49190, P50133, P51839, P70555, P79222, P97751, Q02643, Q02644, Q03431, Q0P543, Q1LZF7, Q28992, Q29627

Diamond homologs: A0A2Z2U4G9, A6QP74, O35659, O42602, O42603, O46502, O62772, O95838, P23811, P25107, P25117, P25961, P30082, P30083, P32082, P32215, P32241, P32301, P34998, P34999, P35000, P35347, P35353, P41586, P41587, P41588, P41593, P43218, P43219, P43220, P47866, P47871, P47872, P48546, P48960, P49190, P50133, P70205, P70555, P97751

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	6
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

2830 predictions. Top by Δscore:

Variant	Effect	Δscore
2:119441554:TCA:T	donor_loss	1.0000
2:119441555:CA:C	donor_loss	1.0000
2:119441556:ACCT:A	donor_gain	1.0000
2:119441556:ACCTC:A	donor_gain	1.0000
2:119441557:C:CA	donor_loss	1.0000
2:119441557:CCTC:C	donor_gain	1.0000
2:119441557:CCTCC:C	donor_gain	1.0000
2:119441604:C:CT	acceptor_gain	1.0000
2:119441604:C:T	acceptor_gain	1.0000
2:119441605:A:T	acceptor_gain	1.0000
2:119461881:T:A	donor_gain	1.0000
2:119464118:ATTAC:A	donor_gain	1.0000
2:119464121:AC:A	donor_gain	1.0000
2:119464122:CC:C	donor_gain	1.0000
2:119524151:TCA:T	donor_loss	1.0000
2:119524152:CA:C	donor_loss	1.0000
2:119524153:A:AC	donor_gain	1.0000
2:119524154:C:CC	donor_gain	1.0000
2:119441557:CCT:C	donor_gain	0.9900
2:119441595:AGTCC:A	acceptor_gain	0.9900
2:119441596:GTCC:G	acceptor_gain	0.9900
2:119441596:GTCCC:G	acceptor_loss	0.9900
2:119441597:TCC:T	acceptor_gain	0.9900
2:119441597:TCCCT:T	acceptor_loss	0.9900
2:119441598:CC:C	acceptor_gain	0.9900
2:119441598:CCC:C	acceptor_gain	0.9900
2:119441599:CC:C	acceptor_gain	0.9900
2:119441600:C:CC	acceptor_gain	0.9900
2:119441600:CTGCC:C	acceptor_loss	0.9900
2:119441601:T:C	acceptor_loss	0.9900

AlphaMissense

2877 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:119441599:C:G	G381R	0.998
2:119441599:C:T	G381R	0.998
2:119452073:C:A	W286C	0.998
2:119452073:C:G	W286C	0.998
2:119464217:A:G	L181P	0.998
2:119461943:A:G	W232R	0.997
2:119461943:A:T	W232R	0.997
2:119473522:C:A	W112C	0.997
2:119473522:C:G	W112C	0.997
2:119461850:A:G	W263R	0.996
2:119461850:A:T	W263R	0.996
2:119465846:C:T	G149D	0.996
2:119478884:C:A	W76C	0.996
2:119478884:C:G	W76C	0.996
2:119461950:G:C	N229K	0.995
2:119461950:G:T	N229K	0.995
2:119464174:C:A	K195N	0.995
2:119464174:C:G	K195N	0.995
2:119478902:C:A	W70C	0.995
2:119478902:C:G	W70C	0.995
2:119441598:C:T	G381E	0.994
2:119446853:G:C	P349R	0.994
2:119464227:G:C	H178D	0.994
2:119465847:C:G	G149R	0.994
2:119441573:G:C	C389W	0.993
2:119441575:A:G	C389R	0.993
2:119446845:C:G	G352R	0.993
2:119448775:A:C	N309K	0.993
2:119448775:A:T	N309K	0.993
2:119461930:T:A	E236V	0.993

dbSNP variants (sampled 300 via entrez): RS1000052518 (2:119439960 C>T), RS1000062475 (2:119506400 A>G), RS1000083919 (2:119480611 G>A), RS1000121804 (2:119480868 A>G), RS1000140229 (2:119497621 A>C), RS1000165717 (2:119500468 A>C), RS1000193177 (2:119485391 T>G), RS1000257049 (2:119524566 C>G), RS1000259879 (2:119474845 C>G), RS1000309329 (2:119524768 T>G), RS1000339759 (2:119494804 G>A), RS1000394309 (2:119489161 G>C), RS1000397533 (2:119490561 A>G), RS1000425609 (2:119489436 G>A,C), RS1000430323 (2:119490840 T>C)

Disease associations

OMIM: gene MIM:182098 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST007847_120	Type 2 diabetes	2.000000e-08
GCST008103_94	Bipolar disorder	2.000000e-06
GCST010118_15	Type 2 diabetes	7.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1925 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds).

Molecule	Name	Phase	Patents
CHEMBL6067494	SECRETIN	4

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Glucagon receptor family

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
secretin	Full agonist	9.7	pEC50
[125I]secretin (pig)	Full agonist	9.2	pKd
secretin	Agonist	9.0	pIC50
secretin	Full agonist	9.0	pKi
[Arg16]chicken secretin	Agonist	7.7	pIC50
[Bpa6,Tyr10]secretin-27 (rat)	Full agonist	7.6	pKd
VIP	Partial agonist	5.4	pIC50
[(CH2NH)4,5]secretin	Antagonist	5.3	pKi
secretin-(5-27) (pig)	Full agonist	5.0	pIC50

ChEMBL bioactivities

17 potent at pChembl≥5 of 17 total, top 17 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.10	EC50	0.08	nM	SECRETIN
10.00	EC50	0.1	nM	CHEMBL1256314
8.46	Ki	3.5	nM	SECRETIN
7.96	Ki	11	nM	CHEMBL1256314
7.39	EC50	40.55	nM	PURMORPHAMINE
7.17	EC50	68.08	nM	PURMORPHAMINE
7.11	EC50	78.1	nM	CHEMBL5396976
7.10	EC50	80.2	nM	CHEMBL5423791
7.10	EC50	80.2	nM	CHEMBL5418444
7.10	EC50	79.1	nM	CHEMBL5434238
7.09	EC50	80.6	nM	CHEMBL5408063
7.07	EC50	85.51	nM	PURMORPHAMINE
7.07	EC50	84.4	nM	CHEMBL5429270
7.06	EC50	87.5	nM	CHEMBL5432045
7.04	EC50	91.1	nM	CHEMBL5404963
6.72	EC50	190	nM	CHEMBL5567643
6.10	EC50	800	nM	CHEMBL5560755

PubChem BioAssay actives

15 with measured affinity, of 37 total; 12 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
(3S)-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[2-[[(2S)-1-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(4R,7S,10R)-10-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-7-(hydroxymethyl)-6,9-dioxo-1,2-dithia-5,8-diazacycloundecane-4-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-5-oxopentanoyl]amino]-4-oxobutanoic acid	517108: Agonist activity at secretin receptor expressed in CHO cells assessed as increase of cAMP level	ec50	0.0001	uM
9-cyclohexyl-N-(4-morpholin-4-ylphenyl)-2-naphthalen-1-yloxypurin-6-amine	1999693: Positive allosteric modulation of SCTR (unknown origin) expressed in CHO cells assessed as potentiation of SCT-induced cAMP production by measuring secretin EC50 at 10 uM incubated for 20 mins in presence of 1 uM SCT by Lance cAMP assay (Rvb = 7.77 +/- 0.116 No_unit)	ec50	0.0406	uM
7-cyclohexyl-4-(4-morpholin-4-ylanilino)-2-naphthalen-1-yloxypyrrolo[2,3-d]pyrimidine-5-carboxylic acid	1999697: Positive allosteric modulation of SCTR (unknown origin) overexpressed in CHO cells assessed as potentiation of SCT-induced cAMP production by measuring secretin EC50 at 100 uM incubated for 20 mins by Lance cAMP assay	ec50	0.0781	uM
9-cyclohexyl-2-naphthalen-1-yloxy-N-(4-naphthalen-1-ylphenyl)purin-6-amine	1999698: Negative allosteric modulation of SCTR (unknown origin) overexpressed in CHO cells assessed as decrease in SCT-induced cAMP production by measuring secretin EC50 at 100 uM incubated for 20 mins by Lance cAMP assay	ec50	0.0791	uM
5-[9-cyclohexyl-6-(4-morpholin-4-ylanilino)purin-2-yl]oxynaphthalen-2-ol	1999697: Positive allosteric modulation of SCTR (unknown origin) overexpressed in CHO cells assessed as potentiation of SCT-induced cAMP production by measuring secretin EC50 at 100 uM incubated for 20 mins by Lance cAMP assay	ec50	0.0802	uM
2-[(9-cyclohexyl-2-naphthalen-1-yloxypurin-6-yl)amino]-5-morpholin-4-ylphenol	1999697: Positive allosteric modulation of SCTR (unknown origin) overexpressed in CHO cells assessed as potentiation of SCT-induced cAMP production by measuring secretin EC50 at 100 uM incubated for 20 mins by Lance cAMP assay	ec50	0.0802	uM
9-cyclohexyl-2-naphthalen-1-yloxy-N-(4-phenoxyphenyl)purin-6-amine	1999697: Positive allosteric modulation of SCTR (unknown origin) overexpressed in CHO cells assessed as potentiation of SCT-induced cAMP production by measuring secretin EC50 at 100 uM incubated for 20 mins by Lance cAMP assay	ec50	0.0806	uM
cis-(1R,3S)-3-[6-(4-morpholin-4-ylanilino)-2-naphthalen-1-yloxypurin-9-yl]cyclohexan-1-ol	1999697: Positive allosteric modulation of SCTR (unknown origin) overexpressed in CHO cells assessed as potentiation of SCT-induced cAMP production by measuring secretin EC50 at 100 uM incubated for 20 mins by Lance cAMP assay	ec50	0.0844	uM
9-cyclohexyl-2-naphthalen-1-yloxy-N-(4-phenylphenyl)purin-6-amine	1999698: Negative allosteric modulation of SCTR (unknown origin) overexpressed in CHO cells assessed as decrease in SCT-induced cAMP production by measuring secretin EC50 at 100 uM incubated for 20 mins by Lance cAMP assay	ec50	0.0875	uM
1-[4-[(9-cyclohexyl-2-naphthalen-1-yloxypurin-6-yl)amino]phenyl]piperidin-4-ol	1999697: Positive allosteric modulation of SCTR (unknown origin) overexpressed in CHO cells assessed as potentiation of SCT-induced cAMP production by measuring secretin EC50 at 100 uM incubated for 20 mins by Lance cAMP assay	ec50	0.0911	uM
20-[[4-[2-[2-[2-[2-[2-[2-[[(5S)-6-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-methyl-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-5-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino]-2-methylpropanoyl]amino]-4-carboxybutanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-6-oxohexyl]amino]-2-oxoethoxy]ethoxy]ethylamino]-2-oxoethoxy]ethoxy]ethylamino]-1-carboxy-4-oxobutyl]amino]-20-oxoicosanoic acid	2085861: Agonist activity human SCTR stably expressed in CHO-K1 cells assessed as reduction in cAMP accumulation incubated for 30 mins by TR-FRET assay	ec50	0.1900	uM
(4S)-5-[[2-[[(2S,3S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[2-[[(1S)-4-carbamimidamido-1-carboxybutyl]amino]-2-oxoethyl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-2-oxoethyl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-4-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino]propanoyl]amino]-5-oxopentanoic acid	2085861: Agonist activity human SCTR stably expressed in CHO-K1 cells assessed as reduction in cAMP accumulation incubated for 30 mins by TR-FRET assay	ec50	0.8000	uM

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium	decreases expression, increases abundance	2
Nickel	decreases expression	2
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Zoledronic Acid	decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tretinoin	affects expression	1
Triclosan	increases expression	1
Valproic Acid	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

ChEMBL screening assays

20 unique, capped per target: 16 functional, 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1259932	Binding	Displacement of [125I]-secretin-27 from secretin receptor expressed in CHO cells by gamma-spectrometer analysis	Elucidation of the active conformation of the amino terminus of receptor-bound secretin using intramolecular disulfide bond constraints. — Bioorg Med Chem Lett
CHEMBL1259933	Functional	Agonist activity at secretin receptor expressed in CHO cells assessed as increase of cAMP level	Elucidation of the active conformation of the amino terminus of receptor-bound secretin using intramolecular disulfide bond constraints. — Bioorg Med Chem Lett

Cellosaurus cell lines

8 cell lines: 4 spontaneously immortalized cell line, 3 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0TR	ACTOne SCTR	Transformed cell line	Female
CVCL_H498	CHO-K1/SCTR/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KV80	cAMP Hunter CHO-K1 SCTR Gs	Spontaneously immortalized cell line	Female
CVCL_KZ09	PathHunter CHO-K1 SCTR beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KZ66	PathHunter HEK 293 SCTR beta-arrestin	Transformed cell line	Female
CVCL_LB31	PathHunter U2OS SCTR Activated GPCR Internalization	Cancer cell line	Female
CVCL_T423	Psi-CRIP-RxhSecR-bsr	Transformed cell line	Male
CVCL_ZK88	GeneBLAzer SCTR-CRE-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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