SSTR2

Summary

SSTR2 (somatostatin receptor 2, HGNC:11331) is a protein-coding gene on chromosome 17q25.1, encoding Somatostatin receptor type 2 (P30874). Receptor for somatostatin-14 and -28.

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. SSTR2 is a member of the superfamily of receptors having seven transmembrane segments and is expressed in highest levels in cerebrum and kidney.

Source: NCBI Gene 6752 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 41 total
• GTEx eGene: eQTL in 17 tissues, sQTL in 2 (q < 0.05)
• Drug target: yes — 7 curated mechanism-of-action drugs, 3 via a complex or family; 11 molecules with ChEMBL bioactivity (top 3% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 3 — Lanreotide Acetate, Pasireotide Diaspartate, Pasireotide Pamoate
• Approved drugs acting on a complex or family including it: 2 — Lutetium Oxodotreotide Lu-177, Octreotide Acetate (Somatostatin receptor)
• Constraint (gnomAD): pLI 0.14 (intermediate), LOEUF 0.76 (unconstrained)
• MANE Select transcript: NM_001050

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11331
Approved symbol	SSTR2
Name	somatostatin receptor 2
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000180616
Ensembl biotype	protein_coding
OMIM	182452
Entrez	6752

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000357585

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 4: 1

ENST00000357585, ENST00000579323, ENST00001090574, ENST00001143499

RefSeq mRNA: 1 — MANE Select: NM_001050 NM_001050

CCDS: CCDS11691

Canonical transcript exons

ENST00000357585 — 2 exons

Exon	Start	End
ENSE00001425722	73169228	73176633
ENSE00003847255	73165010	73165288

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 90.60.

FANTOM5 (CAGE): breadth broad, TPM avg 9.2622 / max 947.8504, expressed in 629 samples.

Highest expression (Bgee): buccal mucosa cell, ganglionic eminence, cortical plate, cerebellar cortex, cerebellar hemisphere.

Genetic regulation across tissues (GTEx eQTL / sQTL)

SSTR2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 17 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

19 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells EBV-transformed lymphocytes	eqtl	6.5e-13	-0.48	17:73158794:C:A
Adipose Subcutaneous	eqtl	1.9e-11	+0.24	17:72926397:G:A
Brain Cerebellar Hemisphere	eqtl	1.0e-10	-0.31	17:72902951:G:GA
Testis	eqtl	1.9e-07	+0.34	17:73200670:A:G
Thyroid	eqtl	2.8e-07	+0.22	17:72929700:G:C
Brain Frontal Cortex BA9	eqtl	1.5e-06	-0.34	17:73171616:G:T
Brain Cerebellum	eqtl	1.4e-05	-0.29	17:72903550:A:G
Heart Atrial Appendage	eqtl	6.4e-05	+0.26	17:73058174:C:T
Cells Cultured fibroblasts	eqtl	2.9e-04	-0.29	17:73245140:C:T
Skin Sun Exposed Lower leg	eqtl	8.3e-04	+0.15	17:72928673:T:G
Breast Mammary Tissue	eqtl	2.0e-03	+0.20	17:72931510:G:A
Heart Left Ventricle	eqtl	4.2e-03	+0.27	17:74041747:G:A
Nerve Tibial	eqtl	4.6e-03	+0.14	17:73505745:G:T
Skin Not Sun Exposed Suprapubic	eqtl	5.0e-03	+0.16	17:72929700:G:C
Adipose Visceral Omentum	eqtl	5.0e-03	+0.16	17:72926397:G:A
Adipose Visceral Omentum	sqtl	1.3e-02	-1.49	17:72885260:G:A
Brain Cortex	eqtl	1.7e-02	-0.29	17:73163647:G:A
Esophagus Gastroesophageal Junction	eqtl	2.1e-02	+0.20	17:73055397:T:A
Brain Cerebellar Hemisphere	sqtl	2.4e-02	+0.42	17:73168237:G:A

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
162561	9.1891	629
162562	0.0730	41

Top tissues by expression

showing 100 of 281 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	90.60	gold quality
ganglionic eminence	UBERON:0004023	90.13	gold quality
cortical plate	UBERON:0005343	84.51	gold quality
cerebellar cortex	UBERON:0002129	84.38	gold quality
cerebellar hemisphere	UBERON:0002245	84.32	gold quality
cerebellum	UBERON:0002037	83.70	gold quality
islet of Langerhans	UBERON:0000006	83.29	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.05	gold quality
cerebellar vermis	UBERON:0004720	80.03	silver quality
paraflocculus	UBERON:0005351	79.51	gold quality
superior frontal gyrus	UBERON:0002661	79.07	gold quality
prefrontal cortex	UBERON:0000451	78.09	gold quality
postcentral gyrus	UBERON:0002581	78.00	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	77.43	gold quality
frontal cortex	UBERON:0001870	77.25	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.96	gold quality
neocortex	UBERON:0001950	76.86	gold quality
parietal lobe	UBERON:0001872	76.39	gold quality
cingulate cortex	UBERON:0003027	76.31	gold quality
cerebral cortex	UBERON:0000956	76.29	gold quality
anterior cingulate cortex	UBERON:0009835	76.15	gold quality
Brodmann (1909) area 9	UBERON:0013540	75.95	gold quality
entorhinal cortex	UBERON:0002728	75.84	gold quality
Brodmann (1909) area 46	UBERON:0006483	75.38	gold quality
right frontal lobe	UBERON:0002810	75.19	gold quality
cartilage tissue	UBERON:0002418	74.79	gold quality
embryo	UBERON:0000922	74.19	gold quality
telencephalon	UBERON:0001893	74.07	gold quality
nucleus accumbens	UBERON:0001882	74.03	gold quality
Ammon’s horn	UBERON:0001954	73.86	gold quality
tibia	UBERON:0000979	73.68	gold quality
brain	UBERON:0000955	73.56	gold quality
central nervous system	UBERON:0001017	73.14	gold quality
ventricular zone	UBERON:0003053	72.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	72.80	gold quality
forebrain	UBERON:0001890	72.70	gold quality
tongue squamous epithelium	UBERON:0006919	72.52	gold quality
spleen	UBERON:0002106	72.36	gold quality
middle temporal gyrus	UBERON:0002771	72.03	silver quality
metanephros cortex	UBERON:0010533	71.97	gold quality
temporal lobe	UBERON:0001871	71.92	gold quality
pancreatic ductal cell	CL:0002079	71.13	silver quality
middle frontal gyrus	UBERON:0002702	70.51	gold quality
caudate nucleus	UBERON:0001873	70.32	gold quality
tibialis anterior	UBERON:0001385	70.29	silver quality
Brodmann (1909) area 23	UBERON:0013554	70.14	gold quality
amygdala	UBERON:0001876	69.79	gold quality
olfactory bulb	UBERON:0002264	69.78	gold quality
primary visual cortex	UBERON:0002436	69.75	gold quality
CA1 field of hippocampus	UBERON:0003881	69.28	silver quality
ileal mucosa	UBERON:0000331	69.04	silver quality
endothelial cell	CL:0000115	68.91	gold quality
sperm	CL:0000019	68.79	gold quality
occipital lobe	UBERON:0002021	68.77	gold quality
adult mammalian kidney	UBERON:0000082	67.60	gold quality
omental fat pad	UBERON:0010414	67.46	gold quality
peritoneum	UBERON:0002358	67.45	gold quality
male germ cell	CL:0000015	67.36	gold quality
left adrenal gland	UBERON:0001234	67.07	gold quality
adipose tissue of abdominal region	UBERON:0007808	66.42	gold quality
left adrenal gland cortex	UBERON:0035825	66.36	gold quality
putamen	UBERON:0001874	66.15	gold quality
Brodmann (1909) area 10	UBERON:0013541	65.83	gold quality
adrenal cortex	UBERON:0001235	65.79	gold quality
hypothalamus	UBERON:0001898	65.24	gold quality
deltoid	UBERON:0001476	65.17	silver quality
inferior vagus X ganglion	UBERON:0005363	65.16	gold quality
adrenal gland	UBERON:0002369	65.14	gold quality
tongue	UBERON:0001723	64.99	gold quality
trigeminal ganglion	UBERON:0001675	64.98	silver quality
superior vestibular nucleus	UBERON:0007227	64.96	silver quality
pericardium	UBERON:0002407	64.95	gold quality
kidney	UBERON:0002113	64.85	gold quality
nipple	UBERON:0002030	64.81	gold quality
ventral tegmental area	UBERON:0002691	64.69	gold quality
right adrenal gland	UBERON:0001233	64.62	gold quality
dorsal root ganglion	UBERON:0000044	64.59	gold quality
vena cava	UBERON:0004087	64.59	gold quality
superior surface of tongue	UBERON:0007371	64.56	gold quality
cortex of kidney	UBERON:0001225	64.54	gold quality
left uterine tube	UBERON:0001303	64.54	gold quality
body of tongue	UBERON:0011876	64.43	gold quality
pons	UBERON:0000988	64.40	gold quality
substantia nigra pars compacta	UBERON:0001965	64.35	gold quality
pituitary gland	UBERON:0000007	64.34	gold quality
pharyngeal mucosa	UBERON:0000355	64.32	gold quality
synovial joint	UBERON:0002217	64.23	gold quality
lateral nuclear group of thalamus	UBERON:0002736	64.23	gold quality
renal medulla	UBERON:0000362	64.08	silver quality
lateral globus pallidus	UBERON:0002476	64.07	silver quality
right adrenal gland cortex	UBERON:0035827	63.94	gold quality
adenohypophysis	UBERON:0002196	63.74	gold quality
subcutaneous adipose tissue	UBERON:0002190	63.67	gold quality
penis	UBERON:0000989	63.64	gold quality
upper arm skin	UBERON:0004263	63.50	gold quality
fundus of stomach	UBERON:0001160	63.49	gold quality
pancreas	UBERON:0001264	63.39	gold quality
layer of synovial tissue	UBERON:0007616	63.25	gold quality
epithelial cell of pancreas	CL:0000083	63.21	gold quality
trachea	UBERON:0003126	63.11	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	869.82
E-MTAB-5061	yes	25.92
E-GEOD-81547	yes	25.20
E-GEOD-135922	yes	25.16
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Cerebral cortex	tissue	30.5	medium
Somatosensory cortex	tissue	30.5
Prefrontal cortex	tissue	25.1
Motor cortex	tissue	24.7
Frontal cortex	tissue	24.5
Locus coeruleus	tissue	24.5
Occipital cortex	tissue	23.7
Retrosplenial and cingulate cortex	tissue	22.8
Insular cortex	tissue	22.5
Cerebellum	tissue	22.4	high
Hippocampal formation	tissue	21.9
Postcentral gyrus	tissue	21.3
Retrosplenial cortex	tissue	19.4
Temporal cortex	tissue	18.6
Hippocampus	tissue	17.7	not detected
Entorhinal cortex	tissue	17.4
Nucleus accumbens	tissue	16.5
Amygdala	tissue	11.7
Basal ganglia	tissue	9.8	not detected
Putamen	tissue	9.2
Thalamus	tissue	9.1
Caudate putamen	tissue	8.7
Ventral forebrain	tissue	8.0
Septum	tissue	7.2
Hypothalamus	tissue	7.0
Choroid plexus	tissue	6.9
Periaqueductal gray	tissue	5.5
Olfactory bulb	tissue	5.4
Substantia nigra	tissue	4.5
Pons	tissue	4.3
Midbrain	tissue	4.3
Superior colliculi	tissue	4.2
Corpus callosum	tissue	3.8
Spleen	tissue	3.6	not detected
Adrenal gland	tissue	3.3	medium
Stomach 1	tissue	2.9	medium
Medulla oblongata	tissue	2.9
Spinal cord	tissue	2.9
Pituitary gland	tissue	2.6
Kidney	tissue	2.5	medium
Retina	tissue	1.9
Epididymis	tissue	1.5	medium
Seminal vesicle	tissue	1.3	medium
Liver	tissue	1.3	medium
Adipose tissue	tissue	1.2	medium
Duodenum	tissue	1.2	medium
Tonsil	tissue	1.2	medium
Rectum	tissue	1.0	medium
Prostate	tissue	0.9	not detected
Lymph node	tissue	0.8	not detected
Urinary bladder	tissue	0.8	medium
Small intestine	tissue	0.8	medium
Appendix	tissue	0.8	medium
Smooth muscle	tissue	0.7	not detected
Colon	tissue	0.7	medium
Vagina	tissue	0.6	low
Salivary gland	tissue	0.6	medium
Pancreas	tissue	0.6	medium
Bone marrow	tissue	0.6
Endometrium 1	tissue	0.5	low

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Hippocampus, CA1 (24.5), Nucleus of the diagonal band (23.7), Olfactory area (23.5), Perirhinal gyrus (23.4), Septal nuclei (23.1).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIVEP2, PITX1, SMAD3, SMAD4, SP1, TCF4, TP53

miRNA regulators (miRDB)

Targeting SSTR2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 62 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-26A-1-3P	99.64	66.81	788

Functional genomics

gnomAD constraint: pLI 0.144, LOEUF 0.756, missense Z 2.14 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000357585 splits into 4 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
17:73,169,320–73,169,506	75 / 75.4	0.99	no
17:73,169,507–73,169,660	25 / 66.4	0.38	no
17:73,169,661–73,170,301	193 / 273.1	0.71	no
17:73,170,302–73,170,426	71 / 53.8	1.32	no

Literature-anchored findings (GeneRIF, showing 40)

• 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)
• Quantitative evaluation of somatostatin receptor subtype 2 expression in sporadic colorectal tumor and in the corresponding normal mucosa (PMID:11839658)
• Somatostatin modulates G-CSF-induced but not interleukin-3-induced proliferative responses in myeloid 32D cells via activation of somatostatin receptor subtype 2. (PMID:11920268)
• SSTRs 1-5 are heterogeneously expressed in gastroenteropancreatic endocrine tumors (PMID:12021920)
• expression of SSTR2 transcripts up-regulated in prostatic carcinoma cells; SSTR2 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)
• localization and expression in human prostatic tissue and prostate cancer cell lines (PMID:12474541)
• sensitizes human pancreatic cancer cells to death ligand-induced apoptosis (PMID:12490654)
• Presence and intracellular localization of the spliced variant SSR2(a) and its endogenous ligand SS in the cultured human neuroblastoma (NB) cell line, SH-SY5Y. (PMID:12675130)
• study demonstrates for the first time a selective and inducible expression of the recently discovered cortistatin, as well as somatostatin receptor 2, in human monocyte-derived cells (PMID:12684217)
• Expression of somatostatin receptor 2 by human pancreatic cancer causes significant slowing of tumor growth by a mechanism independent of exogenous somatostatin (PMID:14572771)
• Activation of SSTR 2 by SSTR 2 agonist significantly suppressed insulin secretion. (PMID:14576502)
• Sst2 and sst5 were expressed in 70%, sst1 in 50%, and sst3 and sst4 subtypes only in 15-20% of insulinomas (PMID:14602773)
• The receptor from somatostatinoma was completely phosphorylated. Only unphosphorylated sst2A was present in human tumors not exposed to autocrine stimulation. (PMID:14671213)
• SST2R gene together with p53 and ras genes may participate in pancreatic cancerous angiogenesis. (PMID:14695784)
• Expression of reintroduced human SSTR2 gene exerts its antiangiogenic effects by down-regulating expressions of factors involved in tumor angiogenesis and metastasis, suggesting SSTR2 gene transfer as new strategy of gene therapy for pancreatic cancer. (PMID:14760765)
• The degree (or level) of sst2 and sst5 expression is critical for the ultimate GH response of somatotropinomas to endogenous SRIF tone and exogenous SRIF analogue therapy. (PMID:15118275)
• Epithelial sst2A cells, identified as neuroendocrine, gastrin-producing cells, were found in large numbers in the antrum and the duodenum, but not in the gastric corpus. (PMID:15153427)
• SSTR2 provides an anti-angiogenic effect on pancreatic cancer xenografts, susgesting gene transfer as a promising strategy of gene therapy for pancreatic cancer. (PMID:15205362)
• human somatostatin receptor 2 dimers have a role in receptor trafficking (PMID:15231824)
• Expression of the SSTR2 gene in pancreatic adenocarcinoma cells induces apoptosis, which may be mediated via down-regulation of Bcl-2 & up-regulation of Bax (alteration of Bcl-2/Bax ratio) & inhibits tumor angiogenesis, inhibiting of tumor growth. (PMID:15257106)
• gene transfer into pancreatic neoplasm cells resulted in no apoptosis, but a significant cell proliferation inhibition (PMID:15754023)
• SSTR2 and SSTR5 variants seem to have a minor role in determining the responsiveness to somatostatin analogs in acromegaly (PMID:15914528)
• activation of the IKK/NFkappaB signaling cascade by SSTR2 requires a complicated network consisting of Galpha(14), protein kinase C, CamkII, ERK, and c-Src (PMID:16115892)
• In the temporal lobe epilepsy, dentate gyrus, sst2 receptor mRNA expression was strongly increased in the granule cell layer, sst2 receptor-binding sites and immunoreactivity was preserved in the inner but decreased in the outer molecular layer. (PMID:16254490)
• the subtype 2 receptor-mediated antiproliferative effect of SRIH on TT cell proliferation may be exerted through a decrease in cyclin D1 and cdk4 levels (PMID:16601140)
• Sst2 sensitized NIH3T3 cells to TNFalpha-induced apoptosis, enhanced TNFalpha-mediated activation of NF-kappaB, resulting in JNK inhibition and subsequent executioner caspase activation and cell death. (PMID:16645635)
• Physical interaction between a sst2 and p85, revealing a novel mechanism for negative regulation by ligand-activated GPCR of PI3K-dependent survival pathways, which may be an important molecular target for antineoplastic therapy. (PMID:16917505)
• Cytostatic action exerted by SSTR2 analogs might account for the tumor shrinkage observed in acromegalic patients treated with long-acting somatostatin analogs. (PMID:16954443)
• results show that Somatostatin receptor 2 is predominantly expressed on thyroid tissue and is a valid target for treatment of thyroid tumours (PMID:16996150)
• We conclude that the somatostatin receptor plays a role in the total renal uptake of radiolabelled somatostatin analogues. (PMID:17546456)
• Somatostatin caused rapid sst(2a) receptor phosphorylation and desensitization of epithelial antisecretory responses. (PMID:17603546)
• 17q gain and promoter polymorphisms can play a role into the regulation of sst2 expression in neuroblastomas (PMID:17678886)
• The functional interactions between human somatostatin receptor 2 (hSSTR2) and human dopamine receptor 2 (hD2R) in both co-transfected CHO-K1 or HEK-293 cells as well as in cultured neuronal cells which express both the receptors endogenously. (PMID:17706924)
• Analysis of orbital tissues reveals upregulation of SSTR1 and -2 in a group of Graves’ ophthalmopathy (GO) patients. Adipogenesis, a process occurring in GO orbits, provides one possible explanation for some of the observed increase. (PMID:17848636)
• Sst(2) is the best target for visualization of neuroendocrine tumors(NE) tumors, whereas noradrenaline transporter is only a useful target in a subpopulation of NE tumors. (PMID:18196892)
• This study was undertaken to investigate molecular mechanism of transcriptional regulation of the human sst2 gene, for which an additional exon (exon 1) in the 5’-untranslated region was recently found. (PMID:18234910)
• sst2 was expressed in 67% of the patients with HCC (PMID:18292657)
• Existence of a novel upstream promoter for the hSSTR2 gene that is regulated by epigenetic modifications, suggesting for complex control of the hSSTR2 transcription. (PMID:18325993)
• SSTR2 is the predominant mediator of functional ocular antiangiogenic effects. (PMID:18599562)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sstr2a	ENSDARG00000059090
danio_rerio	sstr2b	ENSDARG00000069806
mus_musculus	Sstr2	ENSMUSG00000047904
rattus_norvegicus	Sstr2	ENSRNOG00000002793
drosophila_melanogaster	AstC-R2	FBGN0036789

Paralogs (17): OPRK1 (ENSG00000082556), OPRM1 (ENSG00000112038), KISS1R (ENSG00000116014), OPRD1 (ENSG00000116329), OPRL1 (ENSG00000125510), NPBWR2 (ENSG00000125522), SSTR4 (ENSG00000132671), SSTR1 (ENSG00000139874), SSTR5 (ENSG00000162009), GPR149 (ENSG00000174948), UTS2R (ENSG00000181408), PTGDR2 (ENSG00000183134), CMKLR2 (ENSG00000183671), LTB4R (ENSG00000213903), LTB4R2 (ENSG00000213906), SSTR3 (ENSG00000278195), NPBWR1 (ENSG00000288611)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:98328) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 22 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal retina rod bipolar cell morphology	2
abnormal heart morphology	1
enlarged heart	1
abnormal spleen morphology	1
enlarged spleen	1
small spleen	1
thick skin	1
increased anxiety-related response	1
decreased locomotor activity	1
impaired coordination	1
decreased exploration in new environment	1
increased circulating adrenocorticotropin level	1
abnormal skin morphology	1
abnormal eye morphology	1
abnormal kidney morphology	1
decreased vertical activity	1
small kidney	1
decreased myocardial infarct size	1
abnormal synaptic glutamate release	1
abnormal behavior	1
abnormal brain wave pattern	1
decreased dopamine level	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pan troglodytes	Q5IJ49	100.0%	Diamond
Chlorocebus pygerythrus	Q8HZP3	99.7%	Diamond
Chlorocebus aethiops	Q95L01	99.7%	Diamond
Sus scrofa	P79291	99.6%	Diamond
Macaca fascicularis	Q3BCU0	99.4%	Diamond
Macaca mulatta	Q8HZP2	99.4%	Diamond
Cavia porcellus	P97266	99.0%	Diamond
Canis lupus familiaris	Q49LX5	99.0%	Diamond
Saimiri boliviensis boliviensis	Q5IS84	99.0%	Diamond
Gorilla gorilla gorilla	P79175	98.3%	Diamond
Pongo pygmaeus	P79234	97.9%	Diamond
Meleagris gallopavo	O93361	97.6%	Diamond
Gallus gallus	Q98907	97.6%	Diamond
Xenopus laevis	P79960	97.4%	Diamond
Xenopus tropicalis	Q4VA82	97.4%	Diamond
Bos taurus	P34993	96.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SLC39A11	protein-coding	201266
MTNAP1	protein-coding	55028
CPSF4L	protein-coding	642843
VCF1	protein-coding	84923
COG1	protein-coding	9382
CDC42EP4	protein-coding	23580
LINC00511	ncRNA	400619
SDK2-AS1	ncRNA	101928251
SDK2	protein-coding	54549

Protein

Protein identifiers

Somatostatin receptor type 2 — P30874 (reviewed: P30874)

Alternative names: SRIF-1

All UniProt accessions (1): P30874

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for somatostatin-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and PLC via pertussis toxin insensitive as well as sensitive G proteins. Inhibits calcium entry by suppressing voltage-dependent calcium channels. Acts as the functionally dominant somatostatin receptor in pancreatic alpha- and beta-cells where it mediates the inhibitory effect of somatostatin-14 on hormone secretion. Inhibits cell growth through enhancement of MAPK1 and MAPK2 phosphorylation and subsequent up-regulation of CDKN1B. Stimulates neuronal migration and axon outgrowth and may participate in neuron development and maturation during brain development. Mediates negative regulation of insulin receptor signaling through PTPN6. Inactivates SSTR3 receptor function following heterodimerization.

Subunit / interactions. Homodimer and heterodimer with SSTR3 and SSTR5. Heterodimerization with SSTR3 inactivates SSTR3 receptor function. Heterodimerization with SSTR5 is enhanced by agonist stimulation of SSTR2 and increases SSTR2 cell growth inhibition activity. Following agonist stimulation, homodimers dissociate into monomers which is required for receptor internalization. Interacts with beta-arrestin; this interaction is necessary for receptor internalization and is destabilized by heterodimerization with SSTR5 which results in increased recycling of SSTR2 to the cell surface. Interacts (via C-terminus) with SHANK1 (via PDZ domain).

Subcellular location. Cell membrane. Cytoplasm.

Tissue specificity. Expressed in both pancreatic alpha- and beta-cells (at protein level). Expressed at higher levels in the pancreas than other somatostatin receptors. Also expressed in the cerebrum and kidney and, in lesser amounts, in the jejunum, colon and liver. In the developing nervous system, expressed in the cortex where it is located in the preplate at early stages and is enriched in the outer part of the germinal zone at later stages. In the cerebellum, expressed in the deep part of the external granular layer at gestational week 19. This pattern persists until birth but disappears at adulthood.

Post-translational modifications. Phosphorylated on serine and threonine residues in response to agonist stimulation, leading to receptor desensitization and rapid internalization. Phosphorylated to a greater extent on serine than threonine residues. Threonine phosphorylation is required for arrestin binding and receptor endocytosis but is not necessary for desensitization.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P30874-1	A, SSTR2A	yes
P30874-2	B, SSTR2B

RefSeq proteins (1): NP_001041* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000586	Somatstn_rcpt	Family
IPR002074	Somatstn_rcpt_2	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (68 total): helix 21, topological domain 8, mutagenesis site 8, transmembrane region 7, modified residue 5, strand 5, glycosylation site 4, sequence conflict 3, turn 2, chain 1, site 1, lipid moiety-binding region 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

17 structures by resolution:

PDB	Title	Method	Resolution (Å)
7T10	CryoEM structure of somatostatin receptor 2 in complex with somatostatin-14 and Gi3	ELECTRON MICROSCOPY	2.5
7XN9	Crystal structure of SSTR2 and L-054,522 complex	X-RAY DIFFRACTION	2.6
7XNA	Crystal structure of somatostatin receptor 2 (SSTR2) with peptide antagonist CYN 154806	X-RAY DIFFRACTION	2.65
7T11	CryoEM structure of somatostatin receptor 2 in complex with Octreotide and Gi3.	ELECTRON MICROSCOPY	2.7
7WIG	Cryo-EM structure of the L-054,264-bound human SSTR2-Gi1 complex	ELECTRON MICROSCOPY	2.7
7WIC	Cryo-EM structure of the SS-14-bound human SSTR2-Gi1 complex	ELECTRON MICROSCOPY	2.8
7XAT	Structure of somatostatin receptor 2 bound with SST14.	ELECTRON MICROSCOPY	2.85
7XAV	Structure of somatostatin receptor 2 bound with lanreotide.	ELECTRON MICROSCOPY	2.87
7XAU	Structure of somatostatin receptor 2 bound with octreotide.	ELECTRON MICROSCOPY	2.97
7UL5	CryoEM Structure of Inactive SSTR2 bound to Nb6	ELECTRON MICROSCOPY	3.1
7XMR	CryoEM structure of the somatostatin receptor 2 (SSTR2) in complex with Gi1 and its …	ELECTRON MICROSCOPY	3.1
7YAC	Paltusotine-bound SSTR2-Gi complex	ELECTRON MICROSCOPY	3.24
7Y24	Cryo-EM structure of the octreotide-bound SSTR2-miniGo-scFv16 complex	ELECTRON MICROSCOPY	3.25
7Y26	Cryo-EM structure of the octreotide-bound SSTR2-miniGq-scFv16 complex	ELECTRON MICROSCOPY	3.3
7YAE	Octreotide-bound SSTR2-Gi complex	ELECTRON MICROSCOPY	3.37
7Y27	Cryo-EM structure of the SST-14-bound SSTR2-miniGq-scFv16 complex	ELECTRON MICROSCOPY	3.48
7WJ5	Cryo-EM structure of human somatostatin receptor 2 complex with its agonist somatostatin …	ELECTRON MICROSCOPY	3.72

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30874-F1	81.75	0.54

Antibody-complex structures (SAbDab)

14 antibodies co-crystallized with this protein: 7T10, 7T11, 7UL5, 7WIC, 7WIG, 7WJ5, 7XAT, 7XAU, 7XAV, 7Y24, 7Y26, 7Y27, 7YAC, 7YAE

Human Protein Atlas

Protein class: G-protein coupled receptors, GPCRs excl olfactory receptors, Predicted membrane proteins, GPCRHMM predicted membrane proteins, FDA approved drug targets, Small molecule drugs

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; nucleoplasm

Antibody reliability (HPA): IH uncertain · IF supported

Functional residue map

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

Catalytic / active sites (1)

Position	Role
89	important for ligand binding

Post-translational modifications (6)

Type	Positions
Phosphoserine	341, 343, 348
Phosphothreonine	353, 354
S-palmitoyl cysteine	328

Disulfide bonds (1)

Type	Positions
Disulfide bond	115–193

Glycosylation sites (4)

Type	Positions
N-linked (glcnac…) asparagine	9, 22, 29, 32

Mutagenesis-validated functional residues (8)

Position	Phenotype
89	expression levels reduced by 60%.
89	expression levels reduced by 80%.
89	slightly reduced expression levels. remains localized in membrane. abolishes ligand binding and g protein-mediated calcium release.
139	expression levels reduced by 50%. significantly reduced ligand binding capacity but increased affinity. reduced g protein-mediated camp …
139	expression levels reduced by 40%. no significant change in ligand binding capacity or affinity. reduced g protein-mediated camp signaling …
140	slightly reduced expression levels. no significant change in ligand binding capacity or affinity. no significant change in g …
140	almost abolishes expression. abolishes membrane localization.
140	slightly reduced expression levels. significantly reduced ligand binding capacity but increased affinity. reduced g protein-mediated camp …

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

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

MSigDB gene sets: 176 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_RESPONSE_TO_ESTRADIOL, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_RESPONSE_TO_CORTICOSTEROID, MODULE_64, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, CREB_Q4, MODULE_66, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, MODULE_379, GOBP_CELLULAR_RESPONSE_TO_CORTICOSTEROID_STIMULUS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1

GO Biological Process (8): 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), cellular response to estradiol stimulus (GO:0071392), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), somatostatin signaling pathway (GO:0038170)

GO Molecular Function (5): somatostatin receptor activity (GO:0004994), PDZ domain binding (GO:0030165), neuropeptide binding (GO:0042923), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (5): cytosol (GO:0005829), plasma membrane (GO:0005886), neuron projection (GO:0043005), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

5 top-level categories:

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

30 GO namespaces:

Category	Terms
G protein-coupled receptor signaling pathway	3
cellular anatomical structure	3
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
response to estradiol	1
cellular response to lipid	1
cellular response to oxygen-containing compound	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
signal transduction	1
hormone-mediated signaling pathway	1
somatostatin receptor signaling pathway	1
neuropeptide receptor activity	1
somatostatin signaling pathway	1
protein domain specific binding	1
peptide binding	1
transmembrane signaling receptor activity	1
binding	1
cytoplasm	1
membrane	1
cell periphery	1
plasma membrane bounded cell projection	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 18 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
cytosol	CC	direct assay
PDZ domain binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,112 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SSTR2	SST	P01166	951
SSTR2	HIVEP2	P31629	740
SSTR2	CHGA	P10645	648
SSTR2	FOLH1	Q04609	569
SSTR2	GAST	P01350	568
SSTR2	GCG	P01275	568
SSTR2	TCF4	P15884	552
SSTR2	SYP	P08247	538
SSTR2	POU1F1	P28069	527
SSTR2	POMC	P01189	510
SSTR2	SHANK1	Q9Y566	509
SSTR2	CORT	O00230	499
SSTR2	RET	P07949	496
SSTR2	MEN1	O00255	493
SSTR2	GHRH	P01286	491

IntAct

Human interaction partners of SSTR2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

8 partners by confidence:

Partner	Interaction type	MIscore	Records
PIK3R1	direct interaction	0.640	5
SSTR5	physical association	0.520	4
SSTR3	physical association	0.520	3
ARRB2	colocalization	0.430	2
RAMP1	physical association	0.400	1
RAMP2	physical association	0.400	1
RAMP3	physical association	0.400	1
PJA2	association	0.350	1

BioGRID (16 interactions; top human partners by supporting records): PIK3R1 (Protein-peptide; 4 records), DRD2 (FRET; 3 records), SHANK1 (Reconstituted Complex; 2 records), APP (Reconstituted Complex), CORT (Protein-peptide), ELAVL1 (Affinity Capture-RNA), POLI (Reconstituted Complex), PTPN6 (Affinity Capture-Western), SIRPA (Co-fractionation), SKP2 (Affinity Capture-MS)

SIGNOR signaling

showing 13 of 15 signaling interactions:

A	Effect	B	Mechanism
SSTR2	“up-regulates activity”	GNAI1	binding
SSTR2	“up-regulates activity”	GNAI3	binding
SSTR2	“up-regulates activity”	GNA14	binding
somatostatin	“up-regulates activity”	SSTR2	“chemical activation”
lanreotide	“up-regulates activity”	SSTR2	“chemical activation”
SSTR2	“up-regulates activity”	GNAI2	binding
SSTR2	“up-regulates activity”	GNAZ	binding
SSTR2	“up-regulates activity”	GNAQ	binding
SSTR2	“up-regulates activity”	GNA15	binding
SSTR2	“up-regulates activity”	GNA12	binding
SSTR2	“up-regulates activity”	GNAO1	binding
HIVEP2	“up-regulates quantity by expression”	SSTR2	“transcriptional regulation”
TCF4	“up-regulates quantity by expression”	SSTR2	“transcriptional regulation”

Protein complexes (CORUM) (5)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

5 complexes by size:

Complex	Subunits	Members
★ PDZK1-PLCB3-SSTR2 complex	3	PLCB3, SSTR2, PDZK1
★ DRD2-SSTR2 complex	2	DRD2, SSTR2
★ SSTR1-SSTR2 complex	2	SSTR1, SSTR2
★ SSTR2-SSTR5 complex	2	SSTR2, SSTR5
★ Somatostatin receptor type 2	1	SSTR2

Ligand–receptor pairs (CellPhoneDB) (2)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

2 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
CORT	receptor	Signaling by Somatostatin
SST	receptor	Signaling by Somatostatin

Disease & clinical

Genetic variants

Variant evidence for SSTR2: 41 ClinVar records (0 pathogenic / likely pathogenic); 3 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	3
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 19 predictions of 197):

Position(s)	Effect	Δscore	Sites
17:73165289–73165290	donor_loss	1.0000	5
17:73171612	donor_gain	0.9700
17:73169226–73169227	acceptor_loss	0.9600	6
17:73174310	acceptor_gain	0.9600
17:73169225	acceptor_loss	0.8900
17:73166300	donor_gain	0.8100
17:73174290	acceptor_gain	0.7700
17:73169225	acceptor_loss	0.7500
17:73174292	acceptor_gain	0.7500
17:73170954	donor_gain	0.7100

AlphaMissense

1,108 missense substitutions predicted likely pathogenic (of 2,440 scored), across 260 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M74	9	0.931	0.995
M257	9	0.911	0.994
D89	8	0.998	0.999
N61	8	0.997	0.999
D139	8	0.995	0.999
N308	8	0.983	0.997
D122	8	0.982	0.992
F319	8	0.982	0.999
F265	8	0.967	0.999
F217	8	0.953	0.998
S305	8	0.953	0.998
F110	8	0.949	0.987
F323	8	0.940	0.989
F127	8	0.932	0.997
F208	8	0.930	0.996
F92	8	0.927	0.983
S137	8	0.921	0.999
F98	8	0.904	0.980
N79	8	0.898	0.997
F314	8	0.855	0.980

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (validation)	favorable	4.22e-07
Glioblastoma Multiforme (validation)	favorable	4.25e-05
Rectum Adenocarcinoma (validation)	favorable	0.000102

Disease associations

OMIM: gene MIM:182452 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST009391_406	Metabolite levels	8e-7
GCST004735_39	Epstein-Barr virus copy number in lymphoblastoid cell lines	3e-6
GCST009391_903	Metabolite levels	5e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0010437	triacylglycerol 58:10 measurement
EFO:0010443	triacylglycerol 58:9 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL1804 (SINGLE PROTEIN), CHEMBL2111436 (PROTEIN FAMILY), CHEMBL4296070 (PROTEIN FAMILY)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the SSTR2 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

7 curated-mechanism drugs:

Drug	Modality	Max phase
LANREOTIDE ACETATE	Protein	4
PASIREOTIDE DIASPARTATE	Protein	4
PASIREOTIDE PAMOATE	Protein	4
PALTUSOTINE	Small molecule	3
VAPREOTIDE	Protein	3
ONZIGOLIDE	Unknown	2
VELDOREOTIDE	Protein	2

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes SSTR2 — the drug acts on the assembly or class, not necessarily on this subunit alone.

3 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
LUTETIUM OXODOTREOTIDE LU-177	Somatostatin receptor	5	4
OCTREOTIDE ACETATE	Somatostatin receptor	5	4
SOMATOSTATIN	Somatostatin receptor	5	3

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 20,437 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

11 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1201185	LANREOTIDE	4	184
CHEMBL3349607	PASIREOTIDE	4	109
CHEMBL262135	GALLIUM OXODOTREOTIDE	4
CHEMBL1680	OCTREOTIDE	4	1,041
CHEMBL5267842	PALTUSOTINE	3	89
CHEMBL3349523	VAPREOTIDE	3	14,872
CHEMBL408350	EDOTREOTIDE	3	926
CHEMBL1823872	SOMATOSTATIN	3	2,376
CHEMBL386768	EDOTREOTIDE YTTRIUM	2
CHEMBL5314924	MK-8189	2	14
CHEMBL311695	SEGLITIDE	2	826

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Somatostatin receptors

Most potent curated ligand interactions (77 total), top 25:

Ligand	Action	Affinity	Parameter
L-363,409	Full agonist	12.0	pIC50
L-054,522	Full agonist	11.0	pKi
BIM 23027	Agonist	10.85	pIC50
EC 5-21	Full agonist	10.6	pKi
NC 8-12	Full agonist	10.6	pKi
SRIF-14	Full agonist	10.5	pKi
L-779,976	Full agonist	10.3	pKi
seglitide	Full agonist	10.3	pKi
SRIF-28	Full agonist	10.2	pKi
vapreotide	Full agonist	10.1	pKi
[125I]LTT-SRIF-28	Full agonist	10.0	pKd
octreotide	Full agonist	9.9	pKi
[125I]CGP 23996	Full agonist	9.8	pKd
[Ga-DOTA,Tyr3,Thr8]octreotide	Full agonist	9.7	pIC50
BIM 23197	Full agonist	9.7	pIC50
[125I]BIM23027	Full agonist	9.7	pIC50
paltusotine	Agonist	9.6	pEC50
lanreotide	Full agonist	9.6	pKi
DC 23-60	Full agonist	9.6	pKi
[125I]MK-678	Full agonist	9.6	pKd
BASS antagonist	Antagonist	9.52	pKi
[125I]Tyr10-CST14	Full agonist	9.4	pKd
BIM 23023	Full agonist	9.4	pKi
BIM 23059	Full agonist	9.4	pKi
[125I][Tyr3,Thr8]octreotide	Full agonist	9.33	pIC50

Binding affinities (BindingDB)

984 measured of 1597 human assays (1598 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
CHEMBL4590517	KI	0.013 nM
CHEMBL4541310	KI	0.015 nM
CHEMBL4584764	KI	0.015 nM
CHEMBL4550617	KI	0.015 nM
CHEMBL4564727	KI	0.018 nM
CHEMBL3781796	KI	0.03 nM
CHEMBL4592483	KI	0.061 nM
7-chloro-6-(4-chlorophenyl)-3-(3,5-dimethylphenyl)-4-(2-(piperidin-2-yl)ethoxy)-1,2-dihydroquinoline	KI	0.062 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
CHEMBL4581874	KI	0.075 nM
CHEMBL4556000	KI	0.1 nM
CHEMBL5286005	EC50	0.12 nM
CHEMBL4549303	KI	0.12 nM
CHEMBL4532058	KI	0.12 nM
CHEMBL4862497	EC50	0.12 nM
CHEMBL5279239	EC50	0.14 nM
CHEMBL4563111	KI	0.14 nM
CHEMBL4548228	KI	0.14 nM
CHEMBL3349516	KI	0.158 nM
CHEMBL5283444	EC50	0.16 nM
3-[4-(4-aminopiperidin-1-yl)-3-(3-fluoro-5-methylphenyl)quinolin-6-yl]-2-hydroxybenzonitrile	EC50	0.17 nM	US-10351547: Somatostatin modulators and uses thereof
CHEMBL5279994	EC50	0.17 nM
CHEMBL4581646	KI	0.18 nM
CHEMBL4537192	KI	0.19 nM
CHEMBL3349522	KI	0.2 nM
SRIF	KI	0.2 nM
CHEMBL4206924	IC50	0.2 nM
CHEMBL4212088	IC50	0.2 nM
CHEMBL4214725	IC50	0.2 nM
CHEMBL4205606	IC50	0.2 nM
CHEMBL437296	IC50	0.2 nM
SRIF-D-Trp8	KI	0.23 nM
CHEMBL4210064	IC50	0.24 nM
Cortistatin	KI	0.24 nM
CHEMBL3349521	KI	0.251 nM
CHEMBL4577466	KI	0.26 nM
5-[7-Chloro-3-(3,5-dimethylphenyl)-4-{2-[(2R)-piperidin-2-yl]ethoxy}quinolin-6-yl]pyridin-2(1H)-one	IC50	0.29 nM
CHEMBL440072	KD	0.29 nM
(12S,15R,18S)-9-(4-Amino-butyl)-3-benzyl-15-(4-hydroxy-benzyl)-12-(1H-indol-3-ylmethyl)-6-isopropyl-1,18-dimethyl-1,4,7,10,13,16hexaaza-cyclooctadecane-2,5,8,11,14,17-hexaone	KI	0.3 nM
CHEMBL5273084	EC50	0.31 nM
CHEMBL4205969	IC50	0.31 nM
CHEMBL3098601	KI	0.31 nM
3-[4-(4-aminopiperidin-1-yl)-3-(3,5-difluorophenyl)quinolin-6-yl]-5-fluoro-2-hydroxybenzonitrile	EC50	0.34 nM	US-10351547: Somatostatin modulators and uses thereof
CHEMBL376485	IC50	0.35 nM
(4R,7S,10S,13R,16S,19R)-19-((R)-2-amino-3-(4-hydroxyphenyl)propanamido)-N-((2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl)-7,16-dibenzyl-10-(4-((isopropylamino)methyl)benzyl)-13-(N-methyl-2-naphthamido)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentaazacycloicosane-4-carboxamide	EC50	0.37 nM
Ala-Gly-cyclo[Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys] (SRIF14)	KI	0.38 nM
4-[7-Chloro-3-(3,5-dimethylphenyl)-4-{2-[(2R)-piperidin-2-yl]ethoxy}quinolin-6-yl]phenol	IC50	0.38 nM
3-[4-(3-Aminopropoxy)-7-chloro-3-(3,5-dimethylphenyl)quinolin-6-yl]benzamide	IC50	0.38 nM

ChEMBL bioactivities

1232 potent at pChembl≥5 of 1256 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL99895
10.89	Ki	0.013	nM	CHEMBL4590517
10.89	EC50	0.013	nM	CHEMBL4861425
10.89	EC50	0.013	nM	CHEMBL4872591
10.89	EC50	0.013	nM	CHEMBL4866325
10.85	EC50	0.014	nM	CHEMBL4849848
10.82	Ki	0.015	nM	CHEMBL4541310
10.82	Ki	0.015	nM	CHEMBL4550617
10.82	Ki	0.015	nM	CHEMBL4584764
10.82	EC50	0.015	nM	CHEMBL4860633
10.77	EC50	0.017	nM	CHEMBL4873269
10.74	Ki	0.018	nM	CHEMBL4564727
10.72	EC50	0.019	nM	CHEMBL4853282
10.70	IC50	0.02	nM	CHEMBL3350037
10.70	Ki	0.02	nM	CHEMBL3647695
10.70	Ki	0.02	nM	CHEMBL3647691
10.70	Ki	0.02	nM	CHEMBL3647696
10.66	Ki	0.022	nM	CHEMBL4527856
10.60	Ki	0.025	nM	CHEMBL1766100
10.60	Ki	0.025	nM	CHEMBL1766103
10.57	EC50	0.027	nM	CHEMBL4858892
10.52	Ki	0.03	nM	CHEMBL4299281
10.52	EC50	0.03	nM	CHEMBL4863880
10.52	EC50	0.03	nM	OCTREOTIDE
10.46	Ki	0.035	nM	SOMATOSTATIN
10.43	Ki	0.037	nM	CHEMBL1766097
10.42	Ki	0.038	nM	CHEMBL1766099
10.40	Ki	0.04	nM	CHEMBL3647673
10.40	Ki	0.04	nM	CHEMBL3647704
10.40	Ki	0.04	nM	CHEMBL3647689
10.40	Ki	0.04	nM	CHEMBL3647692
10.40	EC50	0.04	nM	CHEMBL4845867
10.40	Ki	0.04	nM	CHEMBL408362
10.40	Ki	0.04	nM	SOMATOSTATIN
10.39	EC50	0.041	nM	CHEMBL4870834
10.32	EC50	0.048	nM	CHEMBL4862195
10.31	Ki	0.049	nM	SOMATOSTATIN
10.30	Ki	0.05	nM	CHEMBL4110066
10.30	Ki	0.05	nM	CHEMBL3647690
10.30	Ki	0.05	nM	CHEMBL3647700
10.28	Ki	0.053	nM	CHEMBL3350037
10.22	Ki	0.06	nM	CHEMBL3647688
10.21	Ki	0.061	nM	CHEMBL4592483
10.21	Ki	0.062	nM	CHEMBL1766109
10.12	Ki	0.075	nM	CHEMBL4581874
10.11	EC50	0.078	nM	CHEMBL4876263
10.10	Ki	0.08	nM	CHEMBL3647693
10.10	Ki	0.08	nM	CHEMBL3647699
10.10	Ki	0.08	nM	CHEMBL3647684
10.10	EC50	0.08	nM	CHEMBL4851978

PubChem BioAssay actives

986 with measured affinity, of 1599 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-[4-(4-aminopiperidin-1-yl)-5-(3,5-dimethylphenyl)-3-pyridinyl]-3,5-dimethylbenzamide	1781889: Agonist activity at human SSTR2 expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by GloSensor cAMP Assay	ec50	<0.0001	uM
1-[3-(3-fluoro-5-methoxyphenyl)-5-(6-methyl-1H-benzimidazol-2-yl)-4-pyridinyl]piperidin-4-amine	1781889: Agonist activity at human SSTR2 expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by GloSensor cAMP Assay	ec50	<0.0001	uM
1-[3-(6-fluoro-1H-benzimidazol-2-yl)-5-(3-fluoro-5-methylphenyl)-4-pyridinyl]piperidin-4-amine	1781889: Agonist activity at human SSTR2 expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by GloSensor cAMP Assay	ec50	<0.0001	uM
(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-19-[[(2R)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-N-[(2S,3R)-1,3-dihydroxybutan-2-yl]-7-[(1R)-1-hydroxyethyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxamide	254874: Inhibitory concentration against human somatostatin receptor type 2 in CC531 cells	ic50	<0.0001	uM
(4S,7S,10R,13R,16R,19R,22S,25R,28R,31R,34S,37S)-37-[[2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2R)-2-[[(2R)-2-[[(2R)-2-[[(2R)-1-[(2R)-4-amino-2-[[(2R)-2-[[(2R)-4-amino-2-[[(2R)-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]-4-methylsulfanylbutanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-4-carboxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]propanoyl]amino]acetyl]amino]-19,34-bis(4-aminobutyl)-31-(2-amino-2-oxoethyl)-13,25,28-tribenzyl-16,22-bis[(1R)-1-hydroxyethyl]-10-[(1S)-1-hydroxyethyl]-7-(hydroxymethyl)-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	1288210: Displacement of [125I]tyr11-SRIF from human sst2 receptor after 60 mins by liquid scintillation counting method	ki	<0.0001	uM
[(1S,2R,3S,5R,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] (2S)-2-[3-[[(2R)-3-amino-2-[[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-19-[[(2R)-2-amino-3-phenylpropanoyl]amino]-7-[(1R)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]amino]-3-oxopropyl]disulfanyl]propanoyl-methylamino]propanoate	1638693: Displacement of [125I]somatostatin from human SSTR2 expressed in CHO-K1 cell membranes after 240 mins	ki	<0.0001	uM
(2S,3R)-2-[[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-19-[[(2R)-2-[3-[[3-[[(2S)-1-[[(1S,2R,3S,5R,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl]oxy]-1-oxopropan-2-yl]-methylamino]-3-oxopropyl]disulfanyl]propylamino]-3-phenylpropanoyl]amino]-7-[(1R)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]amino]-3-hydroxybutanoic acid	1638693: Displacement of [125I]somatostatin from human SSTR2 expressed in CHO-K1 cell membranes after 240 mins	ki	<0.0001	uM
(2S,3R)-2-[[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-19-[[(2R)-2-amino-3-[4-[2-[[3-[[(2S)-1-[[(1S,2R,3S,5R,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl]oxy]-1-oxopropan-2-yl]-methylamino]-3-oxopropyl]disulfanyl]ethoxy]phenyl]propanoyl]amino]-7-[(1R)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]amino]-3-hydroxybutanoic acid	1638693: Displacement of [125I]somatostatin from human SSTR2 expressed in CHO-K1 cell membranes after 240 mins	ki	<0.0001	uM
[(1S,2R,3S,5R,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] (2S)-2-[3-[[(2R)-2-[[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-19-[[(2R)-2-amino-3-phenylpropanoyl]amino]-7-[(1R)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]amino]-3-hydroxypropyl]disulfanyl]propanoyl-methylamino]propanoate	1638693: Displacement of [125I]somatostatin from human SSTR2 expressed in CHO-K1 cell membranes after 240 mins	ki	<0.0001	uM
[(1S,2R,3S,5R,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] (2S)-2-[3-[[(3R)-4-amino-3-[[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-19-[[(2R)-2-amino-3-phenylpropanoyl]amino]-7-[(1R)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]amino]-2-methyl-4-oxobutan-2-yl]disulfanyl]propanoyl-methylamino]propanoate	1638693: Displacement of [125I]somatostatin from human SSTR2 expressed in CHO-K1 cell membranes after 240 mins	ki	<0.0001	uM
(2R)-2-[[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-19-[[(2R)-2-amino-3-phenylpropanoyl]amino]-7-[(1R)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]amino]-3-[[3-[[(2S)-1-[[(1S,2R,3S,5R,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl]oxy]-1-oxopropan-2-yl]-methylamino]-3-oxopropyl]disulfanyl]propanoic acid	1638693: Displacement of [125I]somatostatin from human SSTR2 expressed in CHO-K1 cell membranes after 240 mins	ki	<0.0001	uM
tert-butyl (2S)-6-amino-2-[[(2R,3S)-3-(1H-indol-3-yl)-2-[[4-(2-oxo-3H-benzimidazol-1-yl)piperidine-1-carbonyl]amino]butanoyl]amino]hexanoate	1954038: Binding affinity to human somatostatin receptor type 2	ki	<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]-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	1061946: Displacement of [125I]-somatostatin from human SSTR2 expressed in CHO-K1 cells	ki	<0.0001	uM
(4R,7S,10S,13S,16S,19S,22R,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	1061946: Displacement of [125I]-somatostatin from human SSTR2 expressed in CHO-K1 cells	ki	<0.0001	uM
1-[3-(3,5-dimethylphenyl)-5-[6-(trifluoromethyl)-1H-benzimidazol-2-yl]-4-pyridinyl]piperidin-4-amine	1781889: Agonist activity at human SSTR2 expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by GloSensor cAMP Assay	ec50	<0.0001	uM
1-[3-(6-chloro-1H-benzimidazol-2-yl)-5-(3,5-dimethylphenyl)-4-pyridinyl]piperidin-4-amine	1781889: Agonist activity at human SSTR2 expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by GloSensor cAMP Assay	ec50	<0.0001	uM
2-[4-(4-aminopiperidin-1-yl)-5-(3,5-dimethylphenyl)-3-pyridinyl]-3H-benzimidazole-5-carbonitrile	1781889: Agonist activity at human SSTR2 expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by GloSensor cAMP Assay	ec50	<0.0001	uM
1-[3-(3,5-dimethoxyphenyl)-5-(6-methyl-1H-benzimidazol-2-yl)-4-pyridinyl]piperidin-4-amine	1781889: Agonist activity at human SSTR2 expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by GloSensor cAMP Assay	ec50	<0.0001	uM
1-[3-(3,5-dimethylphenyl)-5-(6-methyl-1H-benzimidazol-2-yl)-4-pyridinyl]piperidin-4-amine	1781889: Agonist activity at human SSTR2 expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by GloSensor cAMP Assay	ec50	<0.0001	uM
1-[3-(3,5-dimethylphenyl)-5-(6-fluoro-1H-benzimidazol-2-yl)-4-pyridinyl]piperidin-4-amine	1781889: Agonist activity at human SSTR2 expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by GloSensor cAMP Assay	ec50	<0.0001	uM
N-[4-(4-aminopiperidin-1-yl)-5-(3,5-dichlorophenyl)-3-pyridinyl]-2,5-dimethylpyrazole-3-carboxamide	1781889: Agonist activity at human SSTR2 expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by GloSensor cAMP Assay	ec50	<0.0001	uM
4-[7-chloro-3-(3,5-dimethylphenyl)-4-[2-[(2R)-piperidin-2-yl]ethoxy]quinolin-6-yl]benzamide	593731: Displacement of I125-somatostatin-14 from human SST2 expressed in CHO cells after 3 hrs by scintillation counting	ki	<0.0001	uM
3-[7-chloro-3-(3,5-dimethylphenyl)-4-[2-[(2R)-piperidin-2-yl]ethoxy]quinolin-6-yl]phenol	593731: Displacement of I125-somatostatin-14 from human SST2 expressed in CHO cells after 3 hrs by scintillation counting	ki	<0.0001	uM
(4R,7S,10R,13S,16R,19S,22R,25S,28S,31S,34R,37S)-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	203086: Binding affinity towards human sst2 receptor expressed in CHO-K1 cells	ki	<0.0001	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	1638693: Displacement of [125I]somatostatin from human SSTR2 expressed in CHO-K1 cell membranes after 240 mins	ki	<0.0001	uM
Octreotide	1781889: Agonist activity at human SSTR2 expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by GloSensor cAMP Assay	ec50	<0.0001	uM
3-[4-(3-aminopropoxy)-7-chloro-3-(3,5-dimethylphenyl)quinolin-6-yl]phenol	593731: Displacement of I125-somatostatin-14 from human SST2 expressed in CHO cells after 3 hrs by scintillation counting	ki	<0.0001	uM
7-chloro-3-(3,5-dimethylphenyl)-6-(1-methylpyrazol-4-yl)-4-[2-[(2R)-piperidin-2-yl]ethoxy]quinoline	593731: Displacement of I125-somatostatin-14 from human SST2 expressed in CHO cells after 3 hrs by scintillation counting	ki	<0.0001	uM
4-(4-aminopiperidin-1-yl)-N,5-bis(3,5-dimethylphenyl)pyridine-3-carboxamide	1781889: Agonist activity at human SSTR2 expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by GloSensor cAMP Assay	ec50	<0.0001	uM
1-[3-(4,6-dimethyl-1H-benzimidazol-2-yl)-5-(3,5-dimethylphenyl)-4-pyridinyl]piperidin-4-amine	1781889: Agonist activity at human SSTR2 expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by GloSensor cAMP Assay	ec50	<0.0001	uM
1-[3-(1H-benzimidazol-2-yl)-5-(3,5-dimethylphenyl)-4-pyridinyl]piperidin-4-amine	1781889: Agonist activity at human SSTR2 expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by GloSensor cAMP Assay	ec50	0.0001	uM
1-[3-(6-fluoro-1H-benzimidazol-2-yl)-5-(3-fluoro-5-methoxyphenyl)-4-pyridinyl]piperidin-4-amine	1781889: Agonist activity at human SSTR2 expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by GloSensor cAMP Assay	ec50	0.0001	uM
3-(3-chloro-5-methylphenyl)-6-(3-fluoro-5-hydroxyphenyl)-N,7-dimethyl-N-[[(2S)-pyrrolidin-2-yl]methyl]-4H-quinazoline-4-carboxamide	1675011: Agonist activity at SST2 (unknown origin)	ec50	0.0001	uM
6-(3-carbamoyl-5-fluorophenyl)-3-(3-chloro-5-methylphenyl)-N,7-dimethyl-N-[[(2S)-pyrrolidin-2-yl]methyl]-4H-quinazoline-4-carboxamide	1675016: Agonist activity at human SST2 expressed in CHO-K1 cells assessed as reduction in NKH477-induced intracellular cAMP accumulation	ec50	0.0001	uM
[(1S,2R,3S,5R,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] (2S)-2-[3-[2-[[(2S,3R)-2-[[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-19-[[(2R)-2-amino-3-phenylpropanoyl]amino]-7-[(1R)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]amino]-3-hydroxybutanoyl]amino]ethyldisulfanyl]propanoyl-methylamino]propanoate	1638693: Displacement of [125I]somatostatin from human SSTR2 expressed in CHO-K1 cell membranes after 240 mins	ki	0.0001	uM
[(1S,2R,3S,5R,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] (2S)-2-[3-[3-[[(2R)-1-[[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-16-benzyl-4-[[(2R,3R)-1,3-dihydroxybutan-2-yl]carbamoyl]-7-[(1R)-1-hydroxyethyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicos-19-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]propyldisulfanyl]propanoyl-methylamino]propanoate	1638693: Displacement of [125I]somatostatin from human SSTR2 expressed in CHO-K1 cell membranes after 240 mins	ki	0.0001	uM
[(1S,2R,3S,5R,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] (2S)-2-[3-[1-[2-[[(2S)-3-amino-2-[[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-19-[[(2R)-2-amino-3-phenylpropanoyl]amino]-7-[(1R)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]amino]-3-oxopropyl]amino]-2-oxoethyl]-2,5-dioxopyrrolidin-3-yl]sulfanylpropanoyl-methylamino]propanoate	1638693: Displacement of [125I]somatostatin from human SSTR2 expressed in CHO-K1 cell membranes after 240 mins	ki	0.0001	uM
[(1S,2R,3S,5R,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] (2S)-2-[3-[[3-[4-[(2S,5S,8R,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]butylamino]-3-oxopropyl]disulfanyl]propanoyl-methylamino]propanoate	1638693: Displacement of [125I]somatostatin from human SSTR2 expressed in CHO-K1 cell membranes after 240 mins	ki	0.0001	uM
[(1S,2R,3S,5R,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] (2S)-2-[3-[1-[3-[[2-[[(2S)-2-[[(2S)-2-[[2-[6-[3-[3-[[(2R)-1-[[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-16-benzyl-4-[[(2R,3R)-1,3-dihydroxybutan-2-yl]carbamoyl]-7-[(1R)-1-hydroxyethyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicos-19-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]propylsulfanyl]-2,5-dioxopyrrolidin-1-yl]hexanoylamino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]propyl]-2,5-dioxopyrrolidin-3-yl]sulfanylpropanoyl-methylamino]propanoate	1638693: Displacement of [125I]somatostatin from human SSTR2 expressed in CHO-K1 cell membranes after 240 mins	ki	0.0001	uM
[(1S,2R,3S,5R,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] (2S)-2-[[4-[[(2R)-3-amino-2-[[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-19-[[(2R)-2-amino-3-phenylpropanoyl]amino]-7-[(1R)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]amino]-3-oxopropyl]disulfanyl]-4-methylpentanoyl]-methylamino]propanoate	1638693: Displacement of [125I]somatostatin from human SSTR2 expressed in CHO-K1 cell membranes after 240 mins	ki	0.0001	uM
[(1S,2R,3S,5R,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] (2S)-2-[3-[2-[[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-19-[[(2R)-2-amino-3-phenylpropanoyl]amino]-7-[(1R)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]amino]ethyldisulfanyl]propanoyl-methylamino]propanoate	1638693: Displacement of [125I]somatostatin from human SSTR2 expressed in CHO-K1 cell membranes after 240 mins	ki	0.0001	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	203409: Binding affinity towards human Somatostatin receptor type 2 (sst2) using Tyr11-[125I]-SRIF as radioligand was determined in CHO cells	ki	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	203409: Binding affinity towards human Somatostatin receptor type 2 (sst2) using Tyr11-[125I]-SRIF as radioligand was determined in CHO cells	ki	0.0001	uM
3-(3-chloro-5-methylphenyl)-6-(3-fluoro-2-hydroxyphenyl)-N,7-dimethyl-N-(pyrrolidin-2-ylmethyl)-4H-quinazoline-4-carboxamide	1675016: Agonist activity at human SST2 expressed in CHO-K1 cells assessed as reduction in NKH477-induced intracellular cAMP accumulation	ec50	0.0001	uM
N-[4-(4-aminopiperidin-1-yl)-5-(3,5-dichlorophenyl)-3-pyridinyl]-1-methyl-5-(trifluoromethyl)pyrazole-4-carboxamide	1781889: Agonist activity at human SSTR2 expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by GloSensor cAMP Assay	ec50	0.0001	uM
N-[4-(4-aminopiperidin-1-yl)-5-(3,5-dichlorophenyl)-3-pyridinyl]-1,3-dimethylpyrazole-4-carboxamide	1781889: Agonist activity at human SSTR2 expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by GloSensor cAMP Assay	ec50	0.0001	uM
N-[4-(4-aminopiperidin-1-yl)-5-(3,5-dichlorophenyl)-3-pyridinyl]imidazo[1,2-a]pyridine-2-carboxamide	1781889: Agonist activity at human SSTR2 expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by GloSensor cAMP Assay	ec50	0.0001	uM
1-[3-(3-chloro-5-fluorophenyl)-5-(6-fluoro-1H-benzimidazol-2-yl)-4-pyridinyl]piperidin-4-amine	1781889: Agonist activity at human SSTR2 expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by GloSensor cAMP Assay	ec50	0.0001	uM
3-[4-(4-aminopiperidin-1-yl)-3-(3-fluoro-5-methoxyphenyl)quinolin-6-yl]-2-hydroxybenzonitrile	1922701: Agonist activity at human SST2 receptor expressed in CHO-K1 cells assessed as inhibition of NKH477-induced intracellular cAMP accumulation incubated for 20 mins by HTRF assay	ec50	0.0001	uM
3-[4-(4-aminopiperidin-1-yl)-3-(3,5-difluorophenyl)quinolin-6-yl]benzamide	1922701: Agonist activity at human SST2 receptor expressed in CHO-K1 cells assessed as inhibition of NKH477-induced intracellular cAMP accumulation incubated for 20 mins by HTRF assay	ec50	0.0001	uM

CTD chemical–gene interactions

51 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	7
entinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	increases expression	1
propionaldehyde	increases expression	1
terbufos	increases methylation	1
butyraldehyde	increases expression	1
triadimefon	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
Edotreotide	affects binding, decreases reaction	1
AN 238	affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
abrine	increases expression	1
111In-DOTA-TOC	affects binding	1
dorsomorphin	increases expression, decreases expression, affects cotreatment	1
pasireotide	affects binding	1
BIM 23120	increases expression, decreases expression, increases activity	1
64Cu-DOTA-Y3-TATE	affects binding, increases uptake	1
64Cu-CB-TE2A-Y3-TATE	affects cotreatment, decreases reaction, increases chemical synthesis, affects binding, increases uptake	1
64Cu-CB-TE2A-sst2-ANT	increases uptake, affects binding	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Celecoxib	increases expression	1
Arsenic Trioxide	decreases expression	1
Cyclic AMP	affects cotreatment, decreases reaction, increases chemical synthesis	1
Aldehydes	increases expression	1

ChEMBL screening assays

182 unique, capped per target: 149 binding, 28 functional, 5 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1007363	Binding	Binding affinity to human SSTR2A	A synthetic method for peptide-PEG-lipid conjugates: application of octreotide-PEG-DSPE synthesis. — *Bioorg Med Chem Lett*
CHEMBL1212342	Functional	Antagonist activity at human SST2 receptor expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulation by FRET assay	Piperidinyl-nicotinamides as potent and selective somatostatin receptor subtype 5 antagonists. — *Bioorg Med Chem Lett*
CHEMBL4195974	ADMET	Drug uptake in HEK293 cells co-expressing SSTR2 (unknown origin) and RFP assessed as SSTR2-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

9 cell lines: 5 cancer cell line, 4 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1QS	Abcam K-562 SSTR2 KO	Cancer cell line	Female
CVCL_D2MD	Abcam Raji SSTR2 KO	Cancer cell line	Male
CVCL_E2L2	HAP1 SSTR2 (-)	Cancer cell line	Male
CVCL_H500	CHO-K1/SST2/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KV81	cAMP Hunter CHO-K1 SSTR2 Gi	Spontaneously immortalized cell line	Female
CVCL_KZ11	PathHunter CHO-K1 SSTR2 Activated GPCR Internalization	Spontaneously immortalized cell line	Female
CVCL_KZ12	PathHunter CHO-K1 SSTR2 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_WQ61	Abcam Jurkat SSTR2 KO	Cancer cell line	Male
CVCL_ZK22	Tango SSTR2-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for SSTR2 across ~30M SureChEMBL compounds — explore on Sugi Predict.