Target Information
| Target General Information | Top | |||||
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| Target ID |
T16633
(Former ID: TTDC00112)
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| Target Name |
Somatostatin receptor type 1 (SSTR1)
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| Synonyms |
Sst(1); Somatostatin receptor 1; SSTR1; SS1R; SRIF-2
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| Gene Name |
SSTR1
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Cushing syndrome [ICD-11: 5A70] | |||||
| 2 | Stomach cancer [ICD-11: 2B72] | |||||
| Function |
Receptor for somatostatin with higher affinity for somatostatin-14 than -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphataseand Na(+)/H(+) exchanger via pertussis toxin insensitive G proteins.
Click to Show/Hide
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MFPNGTASSPSSSPSPSPGSCGEGGGSRGPGAGAADGMEEPGRNASQNGTLSEGQGSAIL
ISFIYSVVCLVGLCGNSMVIYVILRYAKMKTATNIYILNLAIADELLMLSVPFLVTSTLL RHWPFGALLCRLVLSVDAVNMFTSIYCLTVLSVDRYVAVVHPIKAARYRRPTVAKVVNLG VWVLSLLVILPIVVFSRTAANSDGTVACNMLMPEPAQRWLVGFVLYTFLMGFLLPVGAIC LCYVLIIAKMRMVALKAGWQQRKRSERKITLMVMMVVMVFVICWMPFYVVQLVNVFAEQD DATVSQLSVILGYANSCANPILYGFLSDNFKRSFQRILCLSWMDNAAEEPVDYYATALKS RAYSVEDFQPENLESGGVFRNGTCTSRITTL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
| 1 | Lutetium Lu 177 dotatate | Drug Info | Approved | Neuroendocrine cancer | [2] | |
| 2 | Pasireotide | Drug Info | Approved | Cushing disease | [3], [4] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | FR-121196 | Drug Info | Terminated | Alzheimer disease | [5] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Antagonist | [+] 2 Antagonist drugs | + | ||||
| 1 | Lutetium Lu 177 dotatate | Drug Info | [2] | |||
| 2 | SRA880 | Drug Info | [14] | |||
| Inhibitor | [+] 38 Inhibitor drugs | + | ||||
| 1 | Pasireotide | Drug Info | [1] | |||
| 2 | ODT-8 | Drug Info | [6] | |||
| 3 | Cytotoxin Peptide Conjugate | Drug Info | [10] | |||
| 4 | Des-AA1,2,4,12,13-[D-Trp8]SRIF | Drug Info | [6] | |||
| 5 | Des-AA1,2,4,13-[D-Trp8]SRIF | Drug Info | [6] | |||
| 6 | Des-AA1,2,4,5,13-[D-Trp8]-SRIF | Drug Info | [6] | |||
| 7 | Des-AA1,2,4,5-[D-Trp8]SRIF | Drug Info | [6] | |||
| 8 | Des-AA1,2,5,12,13-[D-Trp8,IAmp9]SRIF | Drug Info | [6] | |||
| 9 | Des-AA1,2,5,12,13-[D-Trp8]SRIF | Drug Info | [6] | |||
| 10 | Des-AA1,2,5-[(NalphaMe)Cys3,D-Nal8,IAmp9]SRIF | Drug Info | [11] | |||
| 11 | Des-AA1,2,5-[(NalphaMe)Cys3,D-Trp8,IAmp9]SRIF | Drug Info | [11] | |||
| 12 | Des-AA1,2,5-[(NalphaMe)D-Nal8,IAmp9]SRIF | Drug Info | [11] | |||
| 13 | Des-AA1,2,5-[(NalphaMe)Lys4,D-Nal8,IAmp9]SRIF | Drug Info | [11] | |||
| 14 | Des-AA1,2,5-[D-Nal8,(NalphaMe)IAmp9,Tyr11]SRIF | Drug Info | [11] | |||
| 15 | Des-AA1,2,5-[D-Nal8,(NalphaMe)IAmp9]SRIF | Drug Info | [11] | |||
| 16 | Des-AA1,2,5-[D-Nal8,IAmp9,(NalphaMe)Cys14]SRIF | Drug Info | [11] | |||
| 17 | Des-AA1,2,5-[D-Nal8,IAmp9,(NalphaMe)Phe11]SRIF | Drug Info | [11] | |||
| 18 | Des-AA1,2,5-[D-Nal8,IAmp9,(NalphaMe)Ser13]SRIF | Drug Info | [11] | |||
| 19 | Des-AA1,2,5-[D-Nal8,IAmp9,(NalphaMe)Thr12]SRIF | Drug Info | [11] | |||
| 20 | Des-AA1,2,5-[D-Nal8,IAmp9]SRIF | Drug Info | [11] | |||
| 21 | Des-AA1,2,5-[D-Trp8,(NalphaMe)IAmp9,Tyr11]SRIF | Drug Info | [11] | |||
| 22 | Des-AA1,2,5-[D-Trp8,(NalphaMe)IAmp9]SRIF | Drug Info | [11] | |||
| 23 | Des-AA1,2,5-[D-Trp8,IAmp9,(NalphaMe)Cys14]SRIF | Drug Info | [11] | |||
| 24 | Des-AA1,2,5-[D-Trp8,IAmp9,(NalphaMe)Ser13]SRIF | Drug Info | [11] | |||
| 25 | Des-AA1,2,5-[D-Trp8,IAmp9,(NalphaMe)Thr12]SRIF | Drug Info | [11] | |||
| 26 | Des-AA1,2,5-[D-Trp8,IAmp9,m-I-Tyr11]Cbm-SRIF | Drug Info | [11] | |||
| 27 | Des-AA1,2,5-[D-Trp8,IAmp9,Tyr11]Cbm-SRIF | Drug Info | [11] | |||
| 28 | Des-AA1,2,5-[D-Trp8,IAmp9]SRIF CH-275 | Drug Info | [11] | |||
| 29 | Des-AA1,2,5-[D-Trp8,Tyr11]SRIF | Drug Info | [11] | |||
| 30 | Des-AA1,2,5-[IAmp9,Tyr11]-SRIF | Drug Info | [11] | |||
| 31 | Des-AA1,4,5,13-[Tyr2,D-Trp8]-SRIF | Drug Info | [6] | |||
| 32 | Des-AA1,5-[Tyr2,D-Trp8,(NalphaMe)IAmp9]Cbm-SRIF | Drug Info | [11] | |||
| 33 | Des-AA1,5-[Tyr2,D-Trp8,(NalphaMe)IAmp9]SRIF | Drug Info | [11] | |||
| 34 | Des-AA1,5-[Tyr2,D-Trp8,IAmp9]Cbm-SRIF | Drug Info | [11] | |||
| 35 | Des-AA1,5-[Tyr2,D-Trp8,IAmp9]SRIF CH-288 | Drug Info | [6] | |||
| 36 | Des-AA5-[D-Trp8]SRIF | Drug Info | [11] | |||
| 37 | SOMATOSTATIN | Drug Info | [13] | |||
| 38 | SRIF-28 | Drug Info | [16] | |||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | FR-121196 | Drug Info | [7], [8] | |||
| 2 | 99mTc-MIP-1407 | Drug Info | [7], [8] | |||
| Agonist | [+] 4 Agonist drugs | + | ||||
| 1 | CGP 23996 | Drug Info | [9] | |||
| 2 | L-797,591 | Drug Info | [12] | |||
| 3 | L-817,818 | Drug Info | [12] | |||
| 4 | SRIF-14 | Drug Info | [15] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| cAMP signaling pathway | hsa04024 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| Growth hormone synthesis, secretion and action | hsa04935 | Affiliated Target |
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| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.49E-01 | Radiality | 1.19E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 8.00E+00 | Topological coefficient | 1.00E+00 | Eccentricity | 14 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | cAMP signaling pathway | |||||
| 2 | Neuroactive ligand-receptor interaction | |||||
| Panther Pathway | [+] 2 Panther Pathways | + | ||||
| 1 | Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway | |||||
| 2 | Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Peptide ligand-binding receptors | |||||
| 2 | G alpha (i) signalling events | |||||
| WikiPathways | [+] 5 WikiPathways | + | ||||
| 1 | SIDS Susceptibility Pathways | |||||
| 2 | GPCRs, Class A Rhodopsin-like | |||||
| 3 | Peptide GPCRs | |||||
| 4 | GPCR ligand binding | |||||
| 5 | GPCR downstream signaling | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 355). | |||||
| REF 2 | 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89. | |||||
| REF 3 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 4 | ClinicalTrials.gov (NCT02527993) Treatment of Hypoglycemia Following Gastric Bypass Surgery. | |||||
| REF 5 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001380) | |||||
| REF 6 | Somatostatin receptor 1 selective analogues: 3. Dicyclic peptides. J Med Chem. 2005 Jan 27;48(2):515-22. | |||||
| REF 7 | Nat Rev Drug Discov. 2013 Feb;12(2):87-90. | |||||
| REF 8 | Pasireotide and octreotide stimulate distinct patterns of sst2A somatostatin receptor phosphorylation. Mol Endocrinol. 2010 Feb;24(2):436-46. | |||||
| REF 9 | Characterisation of human recombinant somatostatin receptors. 1. Radioligand binding studies. Naunyn Schmiedebergs Arch Pharmacol. 1999 Nov;360(5):488-99. | |||||
| REF 10 | An adjustable release rate linking strategy for cytotoxin-peptide conjugates. Bioorg Med Chem Lett. 2003 Mar 10;13(5):799-803. | |||||
| REF 11 | Somatostatin receptor 1 selective analogues: 2. N(alpha)-Methylated scan. J Med Chem. 2005 Jan 27;48(2):507-14. | |||||
| REF 12 | Rapid identification of subtype-selective agonists of the somatostatin receptor through combinatorial chemistry. Science. 1998 Oct 23;282(5389):737-40. | |||||
| REF 13 | Discovery of iodinated somatostatin analogues selective for hsst2 and hsst5 with excellent inhibition of growth hormone and prolactin release from ... J Med Chem. 2005 Oct 20;48(21):6643-52. | |||||
| REF 14 | SRA880, in vitro characterization of the first non-peptide somatostatin sst(1) receptor antagonist. Neurosci Lett. 2004 May 6;361(1-3):132-5. | |||||
| REF 15 | Synthesis and biological activities of potent peptidomimetics selective for somatostatin receptor subtype 2. Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10836-41. | |||||
| REF 16 | Novel octreotide dicarba-analogues with high affinity and different selectivity for somatostatin receptors. J Med Chem. 2010 Aug 26;53(16):6188-97. | |||||
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