SSTR4

Summary

SSTR4 (somatostatin receptor 4, HGNC:11333) is a protein-coding gene on chromosome 20p11.21, encoding Somatostatin receptor type 4 (P31391). Receptor for somatostatin-14.

Somatostatin acts at many sites to inhibit the release of many hormones and other secretory proteins. The biologic effects of somatostatin are probably mediated by a family of G protein-coupled receptors that are expressed in a tissue-specific manner. SSTR4 is a member of the superfamily of receptors having seven transmembrane segments and is expressed in highest levels in fetal and adult brain and lung.

Source: NCBI Gene 6754 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 69 total
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001052

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11333
Approved symbol	SSTR4
Name	somatostatin receptor 4
Location	20p11.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000132671
Ensembl biotype	protein_coding
OMIM	182454
Entrez	6754

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000255008

RefSeq mRNA: 1 — MANE Select: NM_001052 NM_001052

CCDS: CCDS42856

Canonical transcript exons

ENST00000255008 — 1 exons

Exon	Start	End
ENSE00000906832	23035312	23039237

Expression profiles

Bgee: expression breadth broad, 35 present calls, max score 68.44.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	68.44	gold quality
metanephric glomerulus	UBERON:0004736	65.85	gold quality
prefrontal cortex	UBERON:0000451	59.75	gold quality
heart right ventricle	UBERON:0002080	57.36	gold quality
frontal cortex	UBERON:0001870	55.82	gold quality
neocortex	UBERON:0001950	54.75	gold quality
right frontal lobe	UBERON:0002810	54.57	gold quality
anterior cingulate cortex	UBERON:0009835	54.47	gold quality
quadriceps femoris	UBERON:0001377	53.62	gold quality
vastus lateralis	UBERON:0001379	53.46	gold quality
cerebellar hemisphere	UBERON:0002245	52.84	gold quality
cerebellar cortex	UBERON:0002129	52.63	gold quality
right hemisphere of cerebellum	UBERON:0014890	52.38	gold quality
Brodmann (1909) area 9	UBERON:0013540	52.15	gold quality
cerebellum	UBERON:0002037	52.05	gold quality
cerebral cortex	UBERON:0000956	51.30	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	51.23	gold quality
Brodmann (1909) area 10	UBERON:0013541	51.03	gold quality
amygdala	UBERON:0001876	50.94	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
islet of Langerhans	UBERON:0000006	49.24	gold quality
thymus	UBERON:0002370	47.61	gold quality
temporal lobe	UBERON:0001871	46.47	gold quality
Ammon’s horn	UBERON:0001954	46.24	gold quality
primary visual cortex	UBERON:0002436	46.01	silver quality
brain	UBERON:0000955	45.80	gold quality
forebrain	UBERON:0001890	45.50	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.82

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 22)

• This suggests that Nbs and the Mre11/Rad50 complex play partially independent roles in telomere protection and that Nbs functions in both ATR- and ATM-controlled telomere protection pathways. (PMID:16648644)
• Study identified a stringent requirement for Mre11-Rad50-Nbs (MRN) function in telomere protection during early embryonic development. (PMID:19520832)
• Drosophila telomere capping protein HOAP interacts with DSB sensor proteins Mre11 and Nbs. (PMID:33556205)
• SSTR transcripts are expressed and functional in retroorbital fibroblasts. SSTR1 is expressed in Grave’s disease and octreotide inhibits retroorbital cell growth, explaining the SRIH therapeutic effect. (PMID:11753241)
• SSTRs 1-5 are heterogeneously expressed in gastroenteropancreatic endocrine tumors (PMID:12021920)
• expression of SSTR4 transcripts up-regulated in prostatic carcinoma cells; SSTR4 agonists may have role in treatment of prostate cancer (PMID:12210479)
• somatostatin receptor transcripts were found in lymphocytes both from Graves’ ophthalmopathy retroorbital tissues and blood samples, with levels of expression of SST1, -2, and -4 mRNA higher than those of the SST3 and -5 transcripts (PMID:12414882)
• A variable degree of SSTR4 was detected in laryngeal benign, premalignant and malignant specimens, with the greatest percentage in teh malignant specimens. (PMID:18066572)
• Immunohistochemistry stufy of SSTR4 in prostate tissue from patients with bladder outlet obstruction showed that close to 90% of secretory cells showed a weak positivity in the cytoplasm. (PMID:18936524)
• In somatotrophinomas patients treated with somatostatin analogs, the most expressed SSTR was SSTR5, SSTR3, SSTR2, SSTR1, and SSTR4, respectively. (PMID:19330452)
• Heterodimerization between somatostatin receptor 4 and somatostatin receptor 5 exerted receptor and ligand specific changes in receptor coupling to adenylyl cyclase and the downstream signaling pathway. (PMID:19426801)
• the expression, localization, and inflammation-induced alterations of sst(4) receptors in murine and human lungs (PMID:19687471)
• Studies show that this study may be the basis for further functional studies to evaluate the role of somatostatin receptors sst1 to sst5 in the diabetic state. (PMID:20182388)
• Evaluation of the potential use of sst5TMD4 expression in surgically removed pituitary adenomas as a predictor of the subsequent response of different pituitary tumors to somatostatin therapy. (PMID:20233783)
• Data show that the mRNA levels of SSTR1, SSTR2, SSTR3, and SSTR5 were high in PET compared with AC, whereas the expression of SSTR4 was low in PET and AC. (PMID:20717067)
• High SSTR4 expression is associated with lymph node metastasis in gallbladder cancer. (PMID:23991955)
• deregulated somatostatin signaling in the Alzheimer disease cortices studied cannot be explained by hypermethylation of the SST or SSTR4 promoter CpG islands. (PMID:24602981)
• this study shows that CD26 is associated with SSTR4 in malignant pleural mesothelioma cells, and this interaction inhibits SSTR4-mediated cytostatic effects. (PMID:24743707)
• An immunohistochemical investigation of the expression of somatostatin receptor subtypes (PMID:25962406)
• Data showed that the distribution of somatostatin receptor (SSTR) subtypes among the 199 pancreatic neuroendocrine tumors (PNETs) was: SSTR2 (54.8%), SSTR1 (53.3%), SSTR4 (51.8%), SSTR5 (33.7%), and SSTR3 (28.6%). (PMID:26474434)
• Characterization of Neurons Expressing the Novel Analgesic Drug Target Somatostatin Receptor 4 in Mouse and Human Brains. (PMID:33096776)
• Human Somatostatin SST4 Receptor Transgenic Mice: Construction and Brain Expression Pattern Characterization. (PMID:33916620)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sstr4	ENSMUSG00000037014
rattus_norvegicus	Sstr4	ENSRNOG00000004641
drosophila_melanogaster	Rh7	FBGN0036260
caenorhabditis_elegans	trhr-1	WBGENE00016265

Paralogs (17): OPRK1 (ENSG00000082556), OPRM1 (ENSG00000112038), KISS1R (ENSG00000116014), OPRD1 (ENSG00000116329), OPRL1 (ENSG00000125510), NPBWR2 (ENSG00000125522), SSTR1 (ENSG00000139874), SSTR5 (ENSG00000162009), GPR149 (ENSG00000174948), SSTR2 (ENSG00000180616), UTS2R (ENSG00000181408), PTGDR2 (ENSG00000183134), CMKLR2 (ENSG00000183671), LTB4R (ENSG00000213903), LTB4R2 (ENSG00000213906), SSTR3 (ENSG00000278195), NPBWR1 (ENSG00000288611)

Protein

Protein identifiers

Somatostatin receptor type 4 — P31391 (reviewed: P31391)

All UniProt accessions (1): P31391

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for somatostatin-14. The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. It is functionally coupled not only to inhibition of adenylate cyclase, but also to activation of both arachidonate release and mitogen-activated protein (MAP) kinase cascade. Mediates antiproliferative action of somatostatin in tumor cells.

Subcellular location. Cell membrane.

Tissue specificity. Specifically expressed in fetal and adult brain, lung tissue, stomach, and in lesser quantities in the kidney, pituitary and adrenals.

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

RefSeq proteins (1): NP_001043* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000586	Somatstn_rcpt	Family
IPR001512	Somatstn_rcpt_4	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (46 total): helix 13, topological domain 8, transmembrane region 7, turn 5, sequence variant 4, strand 4, chain 1, lipid moiety-binding region 1, glycosylation site 1, disulfide bond 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7XMT	ELECTRON MICROSCOPY	2.8
7XMS	ELECTRON MICROSCOPY	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P31391-F1	78.72	0.54

Antibody-complex structures (SAbDab): 2 — 7XMS, 7XMT

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): 327

Disulfide bonds (1): 119–198

Glycosylation sites (1): 24

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-418594	G alpha (i) signalling events
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 71 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_RESPONSE_TO_CORTICOSTEROID, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, GOBP_CELLULAR_RESPONSE_TO_CORTICOSTEROID_STIMULUS, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_RESPONSE_TO_STEROID_HORMONE, GOBP_RESPONSE_TO_HORMONE, GOBP_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_STEROID_HORMONE_STIMULUS, GOMF_PEPTIDE_RECEPTOR_ACTIVITY, GOCC_NEURON_PROJECTION, SAKAI_CHRONIC_HEPATITIS_VS_LIVER_CANCER_DN

GO Biological Process (7): G protein-coupled receptor signaling pathway (GO:0007186), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), neuropeptide signaling pathway (GO:0007218), negative regulation of cell population proliferation (GO:0008285), cellular response to glucocorticoid stimulus (GO:0071385), signal transduction (GO:0007165), somatostatin signaling pathway (GO:0038170)

GO Molecular Function (4): somatostatin receptor activity (GO:0004994), neuropeptide binding (GO:0042923), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), neuron projection (GO:0043005), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	3
G protein-coupled receptor activity	1
signal transduction	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
response to glucocorticoid	1
cellular response to corticosteroid stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
hormone-mediated signaling pathway	1
somatostatin receptor signaling pathway	1
neuropeptide receptor activity	1
somatostatin signaling pathway	1
peptide binding	1
transmembrane signaling receptor activity	1
binding	1
membrane	1
cell periphery	1
plasma membrane bounded cell projection	1
cellular anatomical structure	1

Protein interactions and networks

STRING

858 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SSTR4	SST	P01166	982
SSTR4	PYGB	P11216	748
SSTR4	UTS2	O95399	726
SSTR4	CORT	O00230	659
SSTR4	EPB41L1	Q9H4G0	588
SSTR4	PCSK2	P16519	581
SSTR4	PYGL	P06737	550
SSTR4	HIVEP2	P31629	497
SSTR4	SLC32A1	Q9H598	494
SSTR4	DLG2	Q15700	483
SSTR4	THBD	P07204	459
SSTR4	RET	P07949	452
SSTR4	LPAR3	Q9UBY5	421
SSTR4	SSTR2	P30874	410
SSTR4	SSTR1	P30872	403

IntAct

15 interactions, top by confidence:

A	B	Type	Score
SSTR4	SSTR5	psi-mi:“MI:2364”(proximity)	0.520
SSTR4	SSTR5	psi-mi:“MI:0915”(physical association)	0.520
SSTR4	SSTR5	psi-mi:“MI:0403”(colocalization)	0.520
RAMP1	SSTR4	psi-mi:“MI:0915”(physical association)	0.400
SSTR4	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	SSTR4	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	SSTR4	psi-mi:“MI:0915”(physical association)	0.400
SSTR4	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
SSTR4	YWHAB	psi-mi:“MI:0914”(association)	0.350
SSTR4	SSTR4	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (5): SSTR4 (Affinity Capture-MS), SSTR4 (Negative Genetic), SSTR4 (Positive Genetic), SSTR4 (Affinity Capture-Western), SSTR4 (Protein-peptide)

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: A0T2N3, F1MV99, O00155, O00590, O08707, O08858, O09027, O35210, O77590, O88410, O89039, O97666, P0C5I1, P0C7U4, P11613, P21109, P25024, P25025, P25095, P25104, P25106, P29089, P29754, P29755, P30555, P30556, P30680, P30874, P30875, P30935, P30936, P30937, P30938, P31391, P32303, P32745, P33396, P33535, P34976, P34993

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
SSTR4	“up-regulates activity”	GNAI1	binding
SSTR4	“up-regulates activity”	GNAI3	binding
SSTR4	“up-regulates activity”	GNA12	binding
somatostatin	“up-regulates activity”	SSTR4	“chemical activation”
CORT	up-regulates	SSTR4	binding
SST	up-regulates	SSTR4	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	3
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

103 predictions. Top by Δscore:

Variant	Effect	Δscore
20:23036274:T:TA	donor_gain	0.6700
20:23036261:C:T	donor_gain	0.6100
20:23036314:G:GA	donor_gain	0.4900
20:23036280:T:TA	donor_gain	0.4800
20:23036769:GCA:G	acceptor_gain	0.4600
20:23036191:C:T	donor_gain	0.4100
20:23036769:GC:G	acceptor_gain	0.4100
20:23036297:T:A	acceptor_gain	0.4000
20:23036267:C:CG	donor_gain	0.3900
20:23036614:C:CT	acceptor_gain	0.3700
20:23036768:A:AG	acceptor_gain	0.3700
20:23036769:G:GG	acceptor_gain	0.3700
20:23036275:C:CA	donor_gain	0.3600
20:23036380:TAG:T	acceptor_gain	0.3500
20:23035897:C:A	acceptor_gain	0.3300
20:23036299:G:GT	donor_gain	0.3300
20:23036313:T:TA	donor_gain	0.3300
20:23036766:CCAG:C	acceptor_loss	0.3300
20:23036767:CAG:C	acceptor_loss	0.3300
20:23036768:AGCA:A	acceptor_loss	0.3300
20:23036769:G:GA	acceptor_loss	0.3300
20:23036105:TCGG:T	donor_gain	0.3200
20:23036106:CGGC:C	donor_gain	0.3200
20:23036260:G:GT	donor_gain	0.3200
20:23036298:G:A	acceptor_gain	0.3200
20:23036772:GCCC:G	acceptor_gain	0.3200
20:23036379:TTAGC:T	acceptor_gain	0.3100
20:23036381:AGCTA:A	acceptor_gain	0.3100
20:23036758:T:A	acceptor_loss	0.3100
20:23035905:GC:G	acceptor_gain	0.2900

AlphaMissense

2480 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:23035819:G:C	W112C	0.998
20:23035819:G:T	W112C	0.998
20:23035904:A:C	S141R	0.996
20:23035906:C:A	S141R	0.996
20:23035906:C:G	S141R	0.996
20:23036141:T:C	F220L	0.996
20:23036143:C:A	F220L	0.996
20:23036143:C:G	F220L	0.996
20:23036306:T:C	F275L	0.996
20:23036308:C:A	F275L	0.996
20:23036308:C:G	F275L	0.996
20:23035839:G:A	C119Y	0.995
20:23035874:T:C	F131L	0.995
20:23035876:C:A	F131L	0.995
20:23035876:C:G	F131L	0.995
20:23036285:T:C	F268L	0.995
20:23036287:T:A	F268L	0.995
20:23036287:T:G	F268L	0.995
20:23035747:C:A	N88K	0.994
20:23035747:C:G	N88K	0.994
20:23035838:T:A	C119S	0.994
20:23035839:G:C	C119S	0.994
20:23035994:T:A	W171R	0.994
20:23035994:T:C	W171R	0.994
20:23035678:C:A	N65K	0.993
20:23035678:C:G	N65K	0.993
20:23035880:A:C	S133R	0.993
20:23035882:C:A	S133R	0.993
20:23035882:C:G	S133R	0.993
20:23036138:G:C	G219R	0.993

dbSNP variants (sampled 300 via entrez): RS1001471509 (20:23036776 A>C,G), RS1002549664 (20:23035284 T>G), RS1002865115 (20:23039645 A>G), RS1003531148 (20:23033972 G>T), RS1003933574 (20:23035281 C>A,T), RS1004045189 (20:23038644 G>A), RS1004733076 (20:23039048 C>T), RS1004787848 (20:23035091 G>A), RS1005088691 (20:23037372 T>C), RS1005570219 (20:23034252 T>A), RS1006387619 (20:23037878 G>A), RS1006724208 (20:23036621 A>C,T), RS1007141824 (20:23034973 C>A), RS1007917792 (20:23033374 G>T), RS1007942282 (20:23038928 C>G,T)

Disease associations

OMIM: gene MIM:182454 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001762_256	Obesity-related traits	3.000000e-06
GCST002337_49	Amyotrophic lateral sclerosis (sporadic)	9.000000e-07
GCST003191_1	Vitamin D levels	4.000000e-09
GCST003988_18	Hypothyroidism	5.000000e-10
GCST004250_32	Alanine aminotransferase (ALT) levels after remission induction therapy in actute lymphoblastic leukemia (ALL)	3.000000e-06
GCST004250_48	Alanine aminotransferase (ALT) levels after remission induction therapy in actute lymphoblastic leukemia (ALL)	2.000000e-06
GCST006002_15	Blood sugar levels	2.000000e-13
GCST007393_1	Mitochondrial DNA copy number	6.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0003939	energy intake
EFO:0007965	response to combination chemotherapy
EFO:0004468	glucose measurement
EFO:0006312	mitochondrial DNA measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1853 (SINGLE PROTEIN), CHEMBL2111436 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 18,918 (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
CHEMBL1680	OCTREOTIDE	4	999
CHEMBL262135	GALLIUM OXODOTREOTIDE	4
CHEMBL1823872	SOMATOSTATIN	3	2,276
CHEMBL3349523	VAPREOTIDE	3	14,736
CHEMBL5267842	PALTUSOTINE	3	87
CHEMBL311695	SEGLITIDE	2	820

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Somatostatin receptors

Most potent curated ligand interactions (31 total), top 25:

Ligand	Action	Affinity	Parameter
CST-17	Full agonist	9.6	pKi
[125I]LTT-SRIF-28	Full agonist	9.6	pIC50
[125I]Tyr10-CST14	Full agonist	9.4	pKd
[125I]CGP 23996	Full agonist	9.4	pKd
SRIF-14	Full agonist	9.3	pKi
SRIF-28	Full agonist	9.2	pKi
L-803,087	Full agonist	9.2	pKi
[125I]Tyr11-SRIF-14	Full agonist	9.0	pKd
J-2156	Agonist	8.92	pKi
Des-AA5-[D-Trp8]SRIF	Full agonist	8.9	pIC50
CGP 23996	Full agonist	8.8	pKi
cortistatin-14	Full agonist	8.8	pKi
KE 108	Full agonist	8.8	pIC50
BIM 23052	Full agonist	8.6	pKi
H-c[Cys-Phe-LAgl(NβMe,benzoyl)-Trp-Lys-Thr-Phe-Cys]-OH	Full agonist	8.6	pIC50
BIM 23295	Full agonist	8.5	pKi
H-c[DCys-Phe-LAgl(NβMe,benzoyl)-DTrp-Lys-Thr-Phe-Cys]-OH	Full agonist	8.5	pIC50
H-c[Cys-Phe-LAgl(NβMe,benzoyl)-DTrp-Lys-Thr-Phe-Cys]-OH	Full agonist	8.3	pIC50
NNC269100	Full agonist	8.2	pKi
veldoreotide	Agonist	8.15	pIC50
BIM 23068	Full agonist	8.0	pKi
β3-tetrapeptide	Full agonist	7.8	pKd
consomatin Fj1	Agonist	7.66	pEC50
LY3556050	Agonist	7.4	pKi
L-362,855	Full agonist	7.3	pKi

Binding affinities (BindingDB)

453 measured of 465 human assays (465 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-[[(2R,3S)-2-[[4-[(2-Oxo-2,3-dihydro-1H-benzimidazole)-1-yl]piperidino]carbonylamino]-3-(1H-indole-3-yl)butyryl]amino]-6-aminohexanoic acid tert-butyl ester	KI	0.01 nM
somatostatin-28	KI	0.07 nM
L-Ser-L-Ala-L-Asn-L-Ser-L-Asn-L-Pro-L-Ala-L-Met-L-Ala-L-Pro-L-Arg-L-Glu-L-Arg-L-Lys-L-Ala-Gly-L-Cys(1)-L-Lys-L-Asn-L-Phe-L-Phe-L-Trp-L-Lys-L-Thr-L-Phe-L-Thr-L-Ser-L-Cys(1)-OH	KI	0.07 nM
(1S,5R)-N-[2-(7-chloro-1-methylindazol-3-yl)propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	0.1 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
15-28-Somatostatin-28	KI	0.1 nM
SRIF-D-Trp8	KI	0.23 nM
Cortistatin	KI	0.25 nM
(1R,5S)-N-[2-(7-chloro-1,2-benzoxazol-3-yl)propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	0.3 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
(1R,5S)-N-[2-(7-fluoro-2H-indazol-3-yl)propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	0.3 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
(1S,5R)-N-[2-(1,8-dimethylimidazo[1,5-a]pyridin-3-yl)propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	0.3 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
(1R,5S)-N-[2-(8-chloroimidazo[1,5-a]pyridin-3-yl)propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	0.3 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
(1S,5R)-N-[2-(6-fluoro-1-methylindazol-3-yl)propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	0.4 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
(1R,5S)-N-[2-(7-methyl-1,2-benzoxazol-3-yl)propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	0.4 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
(1S,5R)-N-[2-(7-fluoro-1-methylindazol-3-yl)propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	0.4 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
(1S,5R)-N-[2-(8-methylindolizin-3-yl)propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	0.4 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
Leu8, D-Trp22, Tyr25 SST-28	KI	0.41 nM
(1S,5R)-N-[2-(4-methylphthalazin-1-yl)propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	0.5 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
LTT-SRIF28	KI	0.52 nM
SRIF-D-Trp8	KI	0.56 nM
(1S,5R)-N-[2-methyl-1-[2-(trifluoromethyl)phenoxy]propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	0.6 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
(1R,5S)-N-[2-(3-methylindolizin-1-yl)propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	0.6 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
(1R,5S)-N-[2-(8-methoxyimidazo[1,5-a]pyridin-3-yl)propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	0.6 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
(1R,5S)-N-[2-(8-fluoro-1-methylimidazo[1,5-a]pyridin-3-yl)propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	0.6 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
N-[2-(1-methylisoquinolin-4-yl)propan-2-yl]-2,3,4,5-tetrahydro-1,4-benzoxazepine-9-carboxamide	EC50	0.6 nM	US-10183940: Aryl and heteroaryl-fused tetrahydro-1,4-oxazepine amides as somatostatin receptor subtype 4 (SSTR4) agonists
SRIF-14	KI	0.63 nM
N-[2-(1-methylisoquinolin-4-yl)propan-2-yl]-1,4-oxazepane-6-carboxamide	EC50	0.7 nM	US-10071974: Morpholine and 1,4-oxazepane amides as somatostatin receptor subtype 4 (SSTR4) agonists
(1S,5R)-N-[2-[7-(trifluoromethyl)-2H-indazol-3-yl]propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	0.7 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
SS-25	KI	0.79 nM
(1R,5S)-N-[2-[1-methyl-7-(trifluoromethyl)indazol-3-yl]propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	0.8 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
(1S,5R)-N-[2-(8-methylquinazolin-4-yl)propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	0.8 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
(1S,5R)-N-[1-(8-methylimidazo[1,5-a]pyridin-3-yl)cyclobutyl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	0.8 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
(1S,5R)-N-[2-(6-fluoro-8-methylimidazo[1,5-a]pyridin-3-yl)propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	0.8 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
Cortistatin(1-14)	KI	0.85 nM
(1S,5R)-N-[1-(8-methylimidazo[1,5-a]pyridin-3-yl)cyclopropyl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	0.9 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
(1R,5S)-N-[2-(8-methylimidazo[1,2-a]pyridin-3-yl)propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	0.9 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
N-[2-(6-fluoro-1-methylindazol-3-yl)propan-2-yl]-2,3,4,5-tetrahydro-1,4-benzoxazepine-9-carboxamide	EC50	0.9 nM	US-10183940: Aryl and heteroaryl-fused tetrahydro-1,4-oxazepine amides as somatostatin receptor subtype 4 (SSTR4) agonists
Tyr10-cortistatin	KI	0.91 nM
CST14-Tyr10	KI	0.91 nM
(1R,5S)-N-[1-(4-cyano-2-methylphenoxy)-2-methylpropan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	1 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
(1S,5R)-N-[2-(1-cyclopropyl-8-fluoroimidazo[1,5-a]pyridin-3-yl)propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	1 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
(1R,5S)-N-[2-(1-methylimidazo[1,5-a]pyridin-3-yl)propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	1.2 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
(1R,5S)-N-[2-(1-methyl-4,5,6,7-tetrahydroindazol-3-yl)propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	1.2 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
N-[2-(1-methylisoquinolin-4-yl)propan-2-yl]morpholine-2-carboxamide	EC50	1.3 nM	US-10071974: Morpholine and 1,4-oxazepane amides as somatostatin receptor subtype 4 (SSTR4) agonists
N-[2-(7-methyl-2H-indazol-3-yl)propan-2-yl]-1,4-oxazepane-6-carboxamide	EC50	1.3 nM	US-10071974: Morpholine and 1,4-oxazepane amides as somatostatin receptor subtype 4 (SSTR4) agonists
N-[2-(7-chloro-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-3-yl)propan-2-yl]-2,3,4,5-tetrahydro-1,4-benzoxazepine-9-carboxamide	EC50	1.3 nM	US-10183940: Aryl and heteroaryl-fused tetrahydro-1,4-oxazepine amides as somatostatin receptor subtype 4 (SSTR4) agonists
N-[2-(7-chloro-2H-indazol-3-yl)propan-2-yl]-1,4-oxazepane-6-carboxamide	EC50	1.4 nM	US-10071974: Morpholine and 1,4-oxazepane amides as somatostatin receptor subtype 4 (SSTR4) agonists
(1R,5S)-N-(2-isoquinolin-4-ylpropan-2-yl)-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	1.4 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists
N-(2-naphthalen-1-ylpropan-2-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine-9-carboxamide	EC50	1.4 nM	US-10183940: Aryl and heteroaryl-fused tetrahydro-1,4-oxazepine amides as somatostatin receptor subtype 4 (SSTR4) agonists
L-797591	KI	1.4 nM
(1S,5R)-N-[2-(1-bromoimidazo[1,5-a]pyridin-3-yl)propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	EC50	1.5 nM	US-10166214: Somatostatin receptor subtype 4 (SSTR4) agonists

ChEMBL bioactivities

2044 potent at pChembl≥5 of 2074 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.10	IC50	0.08	nM	SOMATOSTATIN
10.00	EC50	0.1	nM	CHEMBL5197201
10.00	EC50	0.1	nM	CHEMBL5994657
10.00	EC50	0.1	nM	CHEMBL5981217
9.97	EC50	0.1072	nM	CHEMBL5563332
9.90	EC50	0.126	nM	CHEMBL5745719
9.80	EC50	0.158	nM	CHEMBL6005000
9.70	IC50	0.2	nM	CHEMBL437296
9.70	Kd	0.2	nM	CHEMBL440072
9.70	EC50	0.2	nM	CHEMBL5193727
9.70	EC50	0.2	nM	CHEMBL5209180
9.70	EC50	0.2	nM	CHEMBL5805146
9.70	EC50	0.2	nM	CHEMBL6142794
9.52	EC50	0.3	nM	CHEMBL5180543
9.52	EC50	0.3	nM	CHEMBL5190457
9.52	EC50	0.3	nM	CHEMBL5791465
9.52	EC50	0.3	nM	CHEMBL5942606
9.52	EC50	0.3	nM	CHEMBL5868096
9.52	EC50	0.3	nM	CHEMBL5850161
9.52	EC50	0.3	nM	CHEMBL5895650
9.46	IC50	0.35	nM	CHEMBL376485
9.40	EC50	0.4	nM	CHEMBL3421843
9.40	EC50	0.4	nM	CHEMBL3421842
9.40	EC50	0.4	nM	CHEMBL5991272
9.40	EC50	0.4	nM	CHEMBL5813716
9.40	EC50	0.4	nM	CHEMBL6061544
9.40	EC50	0.4	nM	CHEMBL5934220
9.40	EC50	0.4	nM	CHEMBL6037535
9.40	EC50	0.4	nM	CHEMBL6014424
9.40	EC50	0.398	nM	CHEMBL5977345
9.40	Ki	0.4	nM	CHEMBL6161926
9.40	EC50	0.4	nM	CHEMBL6161926
9.34	IC50	0.46	nM	SANDOSTATIN
9.30	IC50	0.5	nM	CHEMBL262379
9.30	IC50	0.5	nM	CHEMBL376484
9.30	EC50	0.5012	nM	CHEMBL4778342
9.30	EC50	0.5	nM	CHEMBL5183772
9.30	Ki	0.5	nM	CHEMBL5197201
9.30	Ki	0.5	nM	CHEMBL5183772
9.30	Ki	0.5	nM	CHEMBL5174969
9.30	EC50	0.5	nM	CHEMBL5966099
9.30	EC50	0.5	nM	CHEMBL5791074
9.29	IC50	0.51	nM	CHEMBL3350911
9.28	IC50	0.53	nM	CHEMBL415582
9.26	IC50	0.55	nM	CHEMBL2371100
9.23	Ki	0.59	nM	SOMATOSTATIN
9.22	IC50	0.6	nM	CHEMBL216992
9.22	EC50	0.6	nM	CHEMBL5177487
9.22	Ki	0.6	nM	CHEMBL5185547
9.22	EC50	0.6	nM	CHEMBL5985852

PubChem BioAssay actives

723 with measured affinity, of 1167 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
(4R,7S,10S,13S,16S,19S,22S,25S,28S,31S,34S,37R)-19,34-bis(4-aminobutyl)-31-(2-amino-2-oxoethyl)-37-[[2-[[(2S)-2-aminopropanoyl]amino]acetyl]amino]-13,25,28-tribenzyl-10,16-bis[(1R)-1-hydroxyethyl]-7-(hydroxymethyl)-22-(1H-indol-3-ylmethyl)-6,9,12,15,18,21,24,27,30,33,36-undecaoxo-1,2-dithia-5,8,11,14,17,20,23,26,29,32,35-undecazacyclooctatriacontane-4-carboxylic acid	203233: Tested for inhibition of radioligand binding to cloned somatostatin receptor hSSTR4	ic50	0.0001	uM
(4R,7S,10S,13S,16S,19S,22S,25S,28S,31S,34S,37R)-19,34-bis(4-aminobutyl)-31-(2-amino-2-oxoethyl)-37-[[2-[[(2S)-2-aminopropanoyl]amino]acetyl]amino]-13,25,28-tribenzyl-10,16-bis[(1R)-1-hydroxyethyl]-22-(1H-indol-3-ylmethyl)-7-methyl-6,9,12,15,18,21,24,27,30,33,36-undecaoxo-1,2-dithia-5,8,11,14,17,20,23,26,29,32,35-undecazacyclooctatriacontane-4-carboxamide	203570: Binding affinity towards human Somatostatin receptor type 4 (sst4) using Tyr11-[125I]-SRIF as radioligand was determined in CHO cells	ki	0.0001	uM
3-[[5-[(3-chlorophenyl)methyl]-4-[3-(1H-imidazol-5-yl)propyl]-1,2,4-triazol-3-yl]methyl]-1H-indole	1881329: Agonist activity at recombinant human SST4 receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP production measured after 2.5 to 20 hrs in presence of 3-isobutyl-1-methylxanthine by TR-FRET LANCE assay	ec50	0.0001	uM
2-(4-chlorophenoxy)-2,2-difluoro-N-[(3S,4S)-3-methylpiperidin-4-yl]acetamide	2094787: Agonist activity at SSTR4 (unknown origin) expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cellular cAMP level incubated for 30 mins by HTRF analysis	ec50	0.0001	uM
6-fluoro-3-[[4-[3-(1H-imidazol-5-yl)propyl]-5-[[3-(trifluoromethyl)phenyl]methyl]-1,2,4-triazol-3-yl]methyl]-1H-indole	1881329: Agonist activity at recombinant human SST4 receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP production measured after 2.5 to 20 hrs in presence of 3-isobutyl-1-methylxanthine by TR-FRET LANCE assay	ec50	0.0002	uM
(4R,7S,10S,13S,16S,19S,22S,25S,28S,31S,34S,37R)-19,34-bis(4-aminobutyl)-37-[[2-[[(2S)-2-aminopropanoyl]amino]acetyl]amino]-13,25,28-tribenzyl-10,16-bis[(1R)-1-hydroxyethyl]-7-(hydroxymethyl)-22-(1H-indol-3-ylmethyl)-31-methyl-6,9,12,15,18,21,24,27,30,33,36-undecaoxo-1,2-dithia-5,8,11,14,17,20,23,26,29,32,35-undecazacyclooctatriacontane-4-carboxamide	203570: Binding affinity towards human Somatostatin receptor type 4 (sst4) using Tyr11-[125I]-SRIF as radioligand was determined in CHO cells	ki	0.0002	uM
(4R,7S,10S,13S,16S,19S,22S,25S,28S,31S,34S,37R)-19,34-bis(4-aminobutyl)-31-(2-amino-2-oxoethyl)-37-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]propanoyl]amino]-13,25,28-tribenzyl-10,16-bis[(1R)-1-hydroxyethyl]-7-(hydroxymethyl)-22-(1H-indol-3-ylmethyl)-6,9,12,15,18,21,24,27,30,33,36-undecaoxo-1,2-dithia-5,8,11,14,17,20,23,26,29,32,35-undecazacyclooctatriacontane-4-carboxamide	203570: Binding affinity towards human Somatostatin receptor type 4 (sst4) using Tyr11-[125I]-SRIF as radioligand was determined in CHO cells	ki	0.0002	uM
6-fluoro-3-[[4-[3-(1H-imidazol-5-yl)propyl]-5-[(2-methoxyphenyl)methyl]-1,2,4-triazol-3-yl]methyl]-1H-indole	1881329: Agonist activity at recombinant human SST4 receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP production measured after 2.5 to 20 hrs in presence of 3-isobutyl-1-methylxanthine by TR-FRET LANCE assay	ec50	0.0002	uM
(4R,7S,10R,13S,16R,19S,22R,25S,28R,31S)-13,28-bis(4-aminobutyl)-25-(2-amino-2-oxoethyl)-31-[[2-[[(2S)-2-aminopropanoyl]amino]acetyl]amino]-19,22-dibenzyl-10-[(1R)-1-hydroxyethyl]-7-(hydroxymethyl)-16-(1H-indol-3-ylmethyl)-6,9,12,15,18,21,24,27,30-nonaoxo-1,2-dithia-5,8,11,14,17,20,23,26,29-nonazacyclodotriacontane-4-carboxylic acid	1638707: Displacement of [125I]somatostatin from human SSTR4 expressed in CHO-K1 cell membranes after 120 mins	kd	0.0002	uM
(2S)-2-[[(2S,3R)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-amino-3-[[2-[2-[(2R,5S,8S,11S,14S,17S)-11-(4-aminobutyl)-17-benzyl-14-[(1R)-1-hydroxyethyl]-5-[(4-hydroxyphenyl)methyl]-8-(1H-indol-3-ylmethyl)-1-methyl-3,6,9,12,15,18-hexaoxo-1,4,7,10,13,16-hexazacyclooctadec-2-yl]ethylsulfanyl]acetyl]amino]propanoyl]amino]-3-(4-aminophenyl)propanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoic acid	280425: Displacement of [125I-Tyr-11]-SRIF from SSTR of human NCI-H69 cell membranes	ic50	0.0002	uM
(4R,7S,10S,13S,16S,19S,22S,25S,28S,31S,34S,37R)-19-(4-aminobutyl)-31-(2-amino-2-oxoethyl)-37-[[2-[[(2S)-2-aminopropanoyl]amino]acetyl]amino]-13,25,28-tribenzyl-10,16-bis[(1R)-1-hydroxyethyl]-7-(hydroxymethyl)-22-(1H-indol-3-ylmethyl)-34-methyl-6,9,12,15,18,21,24,27,30,33,36-undecaoxo-1,2-dithia-5,8,11,14,17,20,23,26,29,32,35-undecazacyclooctatriacontane-4-carboxylic acid	203570: Binding affinity towards human Somatostatin receptor type 4 (sst4) using Tyr11-[125I]-SRIF as radioligand was determined in CHO cells	ki	0.0003	uM
3-[[5-[(3-bromophenyl)methyl]-4-[3-(1H-imidazol-5-yl)propyl]-1,2,4-triazol-3-yl]methyl]-6-fluoro-1H-indole	1881329: Agonist activity at recombinant human SST4 receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP production measured after 2.5 to 20 hrs in presence of 3-isobutyl-1-methylxanthine by TR-FRET LANCE assay	ec50	0.0003	uM
3-[[5-[(3,4-dichlorophenyl)methyl]-4-[3-(1H-imidazol-5-yl)propyl]-1,2,4-triazol-3-yl]methyl]-1H-indole	1881329: Agonist activity at recombinant human SST4 receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP production measured after 2.5 to 20 hrs in presence of 3-isobutyl-1-methylxanthine by TR-FRET LANCE assay	ec50	0.0003	uM
(2S)-6-amino-2-[[(2S)-2-amino-3-[[2-[2-[(2R,5S,8S,11S,14S,17S)-11-(4-aminobutyl)-17-benzyl-14-[(1R)-1-hydroxyethyl]-5-[(4-hydroxyphenyl)methyl]-8-(1H-indol-3-ylmethyl)-1-methyl-3,6,9,12,15,18-hexaoxo-1,4,7,10,13,16-hexazacyclooctadec-2-yl]ethylsulfanyl]acetyl]amino]propanoyl]amino]-N-[(2R)-1-[[(2R,3R)-1,3-dihydroxybutan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]hexanamide	280425: Displacement of [125I-Tyr-11]-SRIF from SSTR of human NCI-H69 cell membranes	ic50	0.0003	uM
(1R,5S)-N-[2-(3-methylisoquinolin-1-yl)propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	1203033: Agonist activity at human somatostatin 4 receptor expressed in H4 cells assessed as inhibition of forskolin-induced intracellular cAMP accumulation incubated for 60 mins by time-resolved fluorescence assay	ec50	0.0004	uM
(1R,5S)-N-[2-(1-methylindazol-3-yl)propan-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxamide	1203033: Agonist activity at human somatostatin 4 receptor expressed in H4 cells assessed as inhibition of forskolin-induced intracellular cAMP accumulation incubated for 60 mins by time-resolved fluorescence assay	ec50	0.0004	uM
(4R,7S,10S,13S,16R,19S,22S,25R)-25-amino-13-(4-aminobutyl)-19,22-dibenzyl-10-[(1R)-1-hydroxyethyl]-7-[(4-hydroxyphenyl)methyl]-16-(1H-indol-3-ylmethyl)-6,9,12,15,18,21,24-heptaoxo-1,2-dithia-5,8,11,14,17,20,23-heptazacyclohexacosane-4-carboxylic acid	203556: Binding affinity towards human somatostatin receptor type 4 using [125I][Leu8,D-Trp22,Tyr25]SRIF-28 as radioligand.	ic50	0.0005	uM
6-(3-chloro-5-methylphenyl)-3-(3-fluoro-5-hydroxyphenyl)-5-[[methyl-[[(2S)-pyrrolidin-2-yl]methyl]amino]methyl]pyrido[2,3-d]pyrimidin-4-one	1675440: Agonist activity at human SST4	ec50	0.0005	uM
3-[[5-[(3-chlorophenyl)methyl]-4-[3-(1H-imidazol-5-yl)propyl]-1,2,4-triazol-3-yl]methyl]-6-fluoro-1H-indole	1881330: Displacement of [125I]-Tyr-SRIF 14 from human SST4 receptor expressed in membrane measured after 90 mins by gamma counting analysis	ki	0.0005	uM
3-[[4-[3-(1H-imidazol-5-yl)propyl]-5-[(3-methoxyphenyl)methyl]-1,2,4-triazol-3-yl]methyl]-1H-indole	1881329: Agonist activity at recombinant human SST4 receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP production measured after 2.5 to 20 hrs in presence of 3-isobutyl-1-methylxanthine by TR-FRET LANCE assay	ec50	0.0005	uM
(4R,7S,10R,13S,16R,19S,22R,25S)-25-amino-13-(4-aminobutyl)-7,22-dibenzyl-10-[(1R)-1-hydroxyethyl]-19-[(4-hydroxyphenyl)methyl]-16-[(1S)-1-naphthalen-2-ylethyl]-6,9,12,15,18,21,24-heptaoxo-1,2-dithia-5,8,11,14,17,20,23-heptazacyclohexacosane-4-carboxylic acid	203555: Binding affinity at human Somatostatin receptor type 4 by [125I][Leu8,D-Trp22,Tyr25]SRIF-28 displacement.	ic50	0.0005	uM
(4R,7S,10R,13S,16R,19S,22S,25S,28R,31R,34S)-34-amino-19,31-bis(4-aminobutyl)-25,28-dibenzyl-10,16-bis[(1R)-1-hydroxyethyl]-7-(hydroxymethyl)-13-[(4-hydroxyphenyl)methyl]-22-(1H-indol-3-ylmethyl)-6,9,12,15,18,21,24,27,30,33-decaoxo-1,2-dithia-5,8,11,14,17,20,23,26,29,32-decazacyclopentatriacontane-4-carboxylic acid	242521: Inhibition of [Leu8,D-Trp22,125I-Tyr25]SRIF-28 binding to human somatostatin receptor type 4	ic50	0.0005	uM
(2S)-2-[[(2S)-2-amino-3-[[2-[2-[(2R,5S,8S,11S,14S,17S)-11-(4-aminobutyl)-17-benzyl-14-[(1R)-1-hydroxyethyl]-5-[(4-hydroxyphenyl)methyl]-8-(1H-indol-3-ylmethyl)-1-methyl-3,6,9,12,15,18-hexaoxo-1,4,7,10,13,16-hexazacyclooctadec-2-yl]ethylsulfanyl]acetyl]amino]propanoyl]amino]-3-(4-aminophenyl)-N-[(2R)-1-[[(2R,3R)-1,3-dihydroxybutan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]propanamide	280425: Displacement of [125I-Tyr-11]-SRIF from SSTR of human NCI-H69 cell membranes	ic50	0.0005	uM
(4R,7S,10S,13S,16R,19S,22S,25S)-25-amino-13-(4-aminobutyl)-7,22-dibenzyl-10-[(1R)-1-hydroxyethyl]-19-[(4-hydroxyphenyl)methyl]-16-[(1S)-1-naphthalen-2-ylethyl]-6,9,12,15,18,21,24-heptaoxo-1,2-dithia-5,8,11,14,17,20,23-heptazacyclohexacosane-4-carboxylic acid	203557: Binding affinity towards human Somatostatin receptor type 4 using 125I-[Leu8,DTrp22,Tyr25]SRIF-28 as radioligand	ic50	0.0006	uM
3-[[4-[3-(1H-imidazol-5-yl)propyl]-5-[[3-(trifluoromethyl)phenyl]methyl]-1,2,4-triazol-3-yl]methyl]-1H-indole	1881329: Agonist activity at recombinant human SST4 receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP production measured after 2.5 to 20 hrs in presence of 3-isobutyl-1-methylxanthine by TR-FRET LANCE assay	ec50	0.0006	uM
(4R,7S,10S,13S,16S,19S,22S,25S,28S,31S,34S,37R)-19,34-bis(4-aminobutyl)-31-(2-amino-2-oxoethyl)-37-[[2-[[(2S)-2-aminopropanoyl]amino]acetyl]amino]-13,25,28-tribenzyl-16-[(1R)-1-hydroxyethyl]-7-(hydroxymethyl)-22-(1H-indol-3-ylmethyl)-10-methyl-6,9,12,15,18,21,24,27,30,33,36-undecaoxo-1,2-dithia-5,8,11,14,17,20,23,26,29,32,35-undecazacyclooctatriacontane-4-carboxamide	203570: Binding affinity towards human Somatostatin receptor type 4 (sst4) using Tyr11-[125I]-SRIF as radioligand was determined in CHO cells	ki	0.0006	uM
6-fluoro-3-[[4-[3-(1H-imidazol-5-yl)propyl]-5-[(3-methoxyphenyl)methyl]-1,2,4-triazol-3-yl]methyl]-1H-indole	1881330: Displacement of [125I]-Tyr-SRIF 14 from human SST4 receptor expressed in membrane measured after 90 mins by gamma counting analysis	ki	0.0006	uM
(4R,7S,10R,13S,16S,19S,22R,25R,28S)-28-amino-13,25-bis(4-aminobutyl)-7,19,22-tribenzyl-10-[(1R)-1-hydroxyethyl]-16-(1H-indol-3-ylmethyl)-6,9,12,15,18,21,24,27-octaoxo-1,2-dithia-5,8,11,14,17,20,23,26-octazacyclononacosane-4-carboxylic acid	242520: Inhibition of 125I-[Leu8,D-Trp22,Tyr25]SRIF-28 binding to human somatostatin receptor type 4	ic50	0.0006	uM
(2S,3R)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-amino-3-[[2-[2-[(2R,5S,8S,11S,14S,17S)-11-(4-aminobutyl)-17-benzyl-14-[(1R)-1-hydroxyethyl]-5-[(4-hydroxyphenyl)methyl]-8-(1H-indol-3-ylmethyl)-1-methyl-3,6,9,12,15,18-hexaoxo-1,4,7,10,13,16-hexazacyclooctadec-2-yl]ethylsulfanyl]acetyl]amino]propanoyl]amino]-3-(4-aminophenyl)propanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxybutanoic acid	280425: Displacement of [125I-Tyr-11]-SRIF from SSTR of human NCI-H69 cell membranes	ic50	0.0006	uM
(4R,7S,10S,13S,16S,19S,22S,25R)-25-amino-13-(4-aminobutyl)-7,19,22-tribenzyl-10-[(1R)-1-hydroxyethyl]-16-(1H-indol-3-ylmethyl)-6,9,12,15,18,21,24-heptaoxo-1,2-dithia-5,8,11,14,17,20,23-heptazacyclohexacosane-4-carboxylic acid	203556: Binding affinity towards human somatostatin receptor type 4 using [125I][Leu8,D-Trp22,Tyr25]SRIF-28 as radioligand.	ic50	0.0007	uM
6-fluoro-3-[[5-[(6-fluoro-1H-indol-3-yl)methyl]-4-[3-(1H-imidazol-5-yl)propyl]-1,2,4-triazol-3-yl]methyl]-1H-indole	1881329: Agonist activity at recombinant human SST4 receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP production measured after 2.5 to 20 hrs in presence of 3-isobutyl-1-methylxanthine by TR-FRET LANCE assay	ec50	0.0007	uM
3-[[4-[3-(1H-imidazol-5-yl)propyl]-5-[(2-methoxyphenyl)methyl]-1,2,4-triazol-3-yl]methyl]-1H-indole	1881330: Displacement of [125I]-Tyr-SRIF 14 from human SST4 receptor expressed in membrane measured after 90 mins by gamma counting analysis	ki	0.0007	uM
6-fluoro-3-[[4-[3-(1H-imidazol-5-yl)propyl]-5-[(3-methylsulfonylphenyl)methyl]-1,2,4-triazol-3-yl]methyl]-1H-indole	1881330: Displacement of [125I]-Tyr-SRIF 14 from human SST4 receptor expressed in membrane measured after 90 mins by gamma counting analysis	ki	0.0007	uM
(4R,7S,10S,13S,16R,19S,22S,25S)-25-acetamido-13-(4-aminobutyl)-7,19,22-tribenzyl-10-[(1R)-1-hydroxyethyl]-16-(1H-indol-3-ylmethyl)-6,9,12,15,18,21,24-heptaoxo-1,2-dithia-5,8,11,14,17,20,23-heptazacyclohexacosane-4-carboxylic acid	384716: Displacement of [125I]-[Leu8, DTrp22, Tyr25]SRIF-28 from human cloned sst4 receptor expressed in CCL39 cells	ic50	0.0007	uM
(4S,7R,10S,13R,16S,19R,22R,25S)-25-amino-13-(4-aminobutyl)-7,19,22-tribenzyl-10-[(1R)-1-hydroxyethyl]-16-(1H-indol-3-ylmethyl)-6,9,12,15,18,21,24-heptaoxo-1,2-dithia-5,8,11,14,17,20,23-heptazacyclohexacosane-4-carboxylic acid	203554: Binding affinity towards human Somatostatin receptor type 4 using 125I-[Leu,DTrp,Tyr]SRIF-28 as radioligand	ic50	0.0007	uM
methyl (2S)-5-(diaminomethylideneamino)-2-[4-(5,7-difluoro-2-phenyl-1H-indol-3-yl)butanoylamino]pentanoate	1571205: Displacement of 3-[125I]iodotyrosyl25-somatostatin-28 from recombinant human SST4 receptor expressed in CHOK1 cell membranes after 45 mins by scintillation counting method	ki	0.0007	uM
1-[(3-chlorophenyl)methyl]-N-[(3S,4S)-3-methylpiperidin-4-yl]cyclopropane-1-carboxamide	2094787: Agonist activity at SSTR4 (unknown origin) expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cellular cAMP level incubated for 30 mins by HTRF analysis	ec50	0.0008	uM
(4R,7S,10S,13S,16S,19S,22S,25R)-25-amino-13-(4-aminobutyl)-7,22-dibenzyl-10-[(1R)-1-hydroxyethyl]-16-(1H-indol-3-ylmethyl)-19-methyl-6,9,12,15,18,21,24-heptaoxo-1,2-dithia-5,8,11,14,17,20,23-heptazacyclohexacosane-4-carboxylic acid	203556: Binding affinity towards human somatostatin receptor type 4 using [125I][Leu8,D-Trp22,Tyr25]SRIF-28 as radioligand.	ic50	0.0008	uM
(4R,7S,10S,13S,16R,19S,22S,25R)-25-amino-13-(4-aminobutyl)-19-[(4-aminophenyl)methyl]-7,22-dibenzyl-10-[(1R)-1-hydroxyethyl]-16-(1H-indol-3-ylmethyl)-6,9,12,15,18,21,24-heptaoxo-1,2-dithia-5,8,11,14,17,20,23-heptazacyclohexacosane-4-carboxylic acid	203556: Binding affinity towards human somatostatin receptor type 4 using [125I][Leu8,D-Trp22,Tyr25]SRIF-28 as radioligand.	ic50	0.0009	uM
6-fluoro-3-[[5-[(4-fluorophenyl)methyl]-4-[3-(1H-imidazol-5-yl)propyl]-1,2,4-triazol-3-yl]methyl]-1H-indole	1881330: Displacement of [125I]-Tyr-SRIF 14 from human SST4 receptor expressed in membrane measured after 90 mins by gamma counting analysis	ki	0.0009	uM
(4R,7S,10S,13S,16S,19S,22S,25R)-13-(4-aminobutyl)-25-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-7,19,22-tribenzyl-10-[(1R)-1-hydroxyethyl]-16-[(1S)-1-(1H-indol-3-yl)ethyl]-6,9,12,15,18,21,24-heptaoxo-1,2-dithia-5,8,11,14,17,20,23-heptazacyclohexacosane-4-carboxylic acid	203556: Binding affinity towards human somatostatin receptor type 4 using [125I][Leu8,D-Trp22,Tyr25]SRIF-28 as radioligand.	ic50	0.0009	uM
(4R,7S,10S,13S,16R,19S,22S,25R)-25-acetamido-13-(4-aminobutyl)-7,19,22-tribenzyl-10-[(1R)-1-hydroxyethyl]-16-(1H-indol-3-ylmethyl)-6,9,12,15,18,21,24-heptaoxo-1,2-dithia-5,8,11,14,17,20,23-heptazacycloheptacosane-4-carboxylic acid	384716: Displacement of [125I]-[Leu8, DTrp22, Tyr25]SRIF-28 from human cloned sst4 receptor expressed in CCL39 cells	ic50	0.0009	uM
(4R,7S,10S,13S,16S,19R,22S,25S,28R)-16-(4-aminobutyl)-10,22,25-tribenzyl-28-[[(2S)-5-carbamimidamido-2-[[2-[2-[2-[[2-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetyl]amino]ethoxy]ethoxy]acetyl]amino]pentanoyl]amino]-13-[(1R)-1-hydroxyethyl]-7-(hydroxymethyl)-19-(1H-indol-3-ylmethyl)-6,9,12,15,18,21,24,27-octaoxo-1,2-dithia-5,8,11,14,17,20,23,26-octazacyclononacosane-4-carboxylic acid	1071306: Displacement of [125I]-[LTT]-SS28 from human SST4 receptor expressed in Chinese hamster CCL-39 cells after 2 hrs by autoradiographic analysis	ic50	0.0009	uM
(4R,7S,10S,13S,16R,19S,22S,25R)-25-amino-13-(4-aminobutyl)-7,22-dibenzyl-10-[(1R)-1-hydroxyethyl]-16-(1H-indol-3-ylmethyl)-19-methyl-6,9,12,15,18,21,24-heptaoxo-1,2-dithia-5,8,11,14,17,20,23-heptazacyclohexacosane-4-carboxylic acid	203556: Binding affinity towards human somatostatin receptor type 4 using [125I][Leu8,D-Trp22,Tyr25]SRIF-28 as radioligand.	ic50	0.0010	uM
(4R,7S,10S,13S,16R,19S,22S,25R)-13-(4-aminobutyl)-19,22-dibenzyl-25-(carbamoylamino)-10-[(1R)-1-hydroxyethyl]-7-[(4-hydroxyphenyl)methyl]-16-(1H-indol-3-ylmethyl)-6,9,12,15,18,21,24-heptaoxo-1,2-dithia-5,8,11,14,17,20,23-heptazacyclohexacosane-4-carboxylic acid	203556: Binding affinity towards human somatostatin receptor type 4 using [125I][Leu8,D-Trp22,Tyr25]SRIF-28 as radioligand.	ic50	0.0010	uM
3-[[4-[3-(1H-imidazol-5-yl)propyl]-5-[(3-methylsulfonylphenyl)methyl]-1,2,4-triazol-3-yl]methyl]-1H-indole	1881330: Displacement of [125I]-Tyr-SRIF 14 from human SST4 receptor expressed in membrane measured after 90 mins by gamma counting analysis	ki	0.0010	uM
3-[[4-[3-(1H-imidazol-5-yl)propyl]-5-[[3-(trifluoromethyl)phenyl]methyl]-1,2,4-triazol-3-yl]methyl]-5-methoxy-1H-indole	1881329: Agonist activity at recombinant human SST4 receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP production measured after 2.5 to 20 hrs in presence of 3-isobutyl-1-methylxanthine by TR-FRET LANCE assay	ec50	0.0010	uM
(4R,7S,10S,13S,16S,19S,22S,25S,28S,31S,34S,37R)-19,34-bis(4-aminobutyl)-31-(2-amino-2-oxoethyl)-37-[[2-[[(2S)-2-aminopropanoyl]amino]acetyl]amino]-25,28-dibenzyl-10,16-bis[(1R)-1-hydroxyethyl]-7-(hydroxymethyl)-22-(1H-indol-3-ylmethyl)-13-methyl-6,9,12,15,18,21,24,27,30,33,36-undecaoxo-1,2-dithia-5,8,11,14,17,20,23,26,29,32,35-undecazacyclooctatriacontane-4-carboxamide	203570: Binding affinity towards human Somatostatin receptor type 4 (sst4) using Tyr11-[125I]-SRIF as radioligand was determined in CHO cells	ki	0.0010	uM
3-[[5-[(3,4-dichlorophenyl)methyl]-4-[3-(1H-imidazol-5-yl)propyl]-1,2,4-triazol-3-yl]methyl]-6-fluoro-1H-indole	1881329: Agonist activity at recombinant human SST4 receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP production measured after 2.5 to 20 hrs in presence of 3-isobutyl-1-methylxanthine by TR-FRET LANCE assay	ec50	0.0010	uM
(4R,7S,10S,13S,16R,19S,22S,25S)-25-amino-13-(4-aminobutyl)-7,19,22-tribenzyl-10-[(1R)-1-hydroxyethyl]-16-(1H-indol-3-ylmethyl)-6,9,12,15,18,21,24-heptaoxo-1,2-dithia-5,8,11,14,17,20,23-heptazacyclohexacosane-4-carboxylic acid	384716: Displacement of [125I]-[Leu8, DTrp22, Tyr25]SRIF-28 from human cloned sst4 receptor expressed in CCL39 cells	ic50	0.0010	uM

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	decreases expression	1
bisphenol A	increases methylation	1
CGP 52608	affects binding, increases reaction	1
pasireotide	affects binding	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Diazinon	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Somatostatin	increases expression	1
Valproic Acid	increases methylation	1

ChEMBL screening assays

174 unique, capped per target: 153 binding, 19 functional, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1009181	Binding	Displacement of [125I]-[Leu8, DTrp22, Tyr25]-somatostatin-28 from human recombinant sst4 receptor expressed in chinese hamster CCL39 cells	Highly potent 4-amino-indolo[2,3-c]azepin-3-one-containing somatostatin mimetics with a range of sst receptor selectivities. — J Med Chem
CHEMBL1177481	Functional	Agonist activity against human SST4 receptor expressed in human NIH373 cells assessed as beta-galactosidase activity at 3 uM after 5 days by R-SAT assay	Optimization of isochromanone based urotensin II receptor agonists. — Bioorg Med Chem
CHEMBL4195976	ADMET	Drug uptake in HEK293 cells co-expressing SSTR4 (unknown origin) and RFP assessed as SSTR4-mediated drug accumulation by measuring mean fluorescence intensity measured after 30 mins by fluorescence microscopic analysis (Rvb = 1.1 No_unit)	New somatostatin-drug conjugates for effective targeting pancreatic cancer. — Bioorg Med Chem

Cellosaurus cell lines

3 cell lines: 3 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_H502	CHO-K1/SST4/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KV83	cAMP Hunter CHO-K1 SSTR4 Gi	Spontaneously immortalized cell line	Female
CVCL_KZ14	PathHunter CHO-K1 SSTR4 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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