Target Information
| Target General Information | Top | |||||
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| Target ID |
T53024
(Former ID: TTDS00394)
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| Target Name |
Somatostatin receptor type 2 (SSTR2)
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| Synonyms |
Sst(2); Somatostatin receptor 2; SS2R; SS2-R; SS-2-R; SRIF-1
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| Gene Name |
SSTR2
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 3 Target-related Diseases | + | ||||
| 1 | Cushing syndrome [ICD-11: 5A70] | |||||
| 2 | Diagnostic imaging [ICD-11: N.A.] | |||||
| 3 | Pituitary gland disorder [ICD-11: 5A60-5A61] | |||||
| 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.
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MDMADEPLNGSHTWLSIPFDLNGSVVSTNTSNQTEPYYDLTSNAVLTFIYFVVCIIGLCG
NTLVIYVILRYAKMKTITNIYILNLAIADELFMLGLPFLAMQVALVHWPFGKAICRVVMT VDGINQFTSIFCLTVMSIDRYLAVVHPIKSAKWRRPRTAKMITMAVWGVSLLVILPIMIY AGLRSNQWGRSSCTINWPGESGAWYTGFIIYTFILGFLVPLTIICLCYLFIIIKVKSSGI RVGSSKRKKSEKKVTRMVSIVVAVFIFCWLPFYIFNVSSVSMAISPTPALKGMFDFVVVL TYANSCANPILYAFLSDNFKKSFQNVLCLVKVSGTDDGERSDSKQDKSRLNETTETQRTL LNGDLQTSI Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T85QFY | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 5 Approved Drugs | + | ||||
| 1 | Copper dotatate Cu-64 | Drug Info | Approved | Diagnostic imaging | [2] | |
| 2 | Ga-68-DOTATOC | Drug Info | Approved | Diagnostic imaging | [3] | |
| 3 | Lanreotide acetate | Drug Info | Approved | Acromegaly | [4], [5], [6] | |
| 4 | Octreotide | Drug Info | Approved | Acromegaly | [7], [8] | |
| 5 | Pasireotide | Drug Info | Approved | Cushing disease | [9], [10] | |
| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | TBR-760 | Drug Info | Phase 2 | Pituitary adenoma | [11] | |
| 2 | PEN-221 | Drug Info | Phase 1/2 | Neuroendocrine cancer | [12] | |
| 3 | Re-188-P-2045 | Drug Info | Phase 1/2 | Lung cancer | [13] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | FR-121196 | Drug Info | Terminated | Alzheimer disease | [14] | |
| Mode of Action | [+] 5 Modes of Action | + | ||||
| Binder | [+] 3 Binder drugs | + | ||||
| 1 | Copper dotatate Cu-64 | Drug Info | [2] | |||
| 2 | Ga-68-DOTATOC | Drug Info | [3] | |||
| 3 | Octreotide | Drug Info | [1] | |||
| Modulator | [+] 5 Modulator drugs | + | ||||
| 1 | Lanreotide acetate | Drug Info | [4], [6] | |||
| 2 | PEN-221 | Drug Info | [12] | |||
| 3 | Re-188-P-2045 | Drug Info | [13] | |||
| 4 | FR-121196 | Drug Info | [18] | |||
| 5 | 99mTc-MIP-1407 | Drug Info | [15] | |||
| Inhibitor | [+] 24 Inhibitor drugs | + | ||||
| 1 | Pasireotide | Drug Info | [15] | |||
| 2 | ODT-8 | Drug Info | [16] | |||
| 3 | Ala11-SRIF-14-amide | Drug Info | [19] | |||
| 4 | Ala6-SRIF-14-amide | Drug Info | [19] | |||
| 5 | Ala7-SRIF-14-amide | Drug Info | [19] | |||
| 6 | Cytotoxin Peptide Conjugate | Drug Info | [21] | |||
| 7 | D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Asp-NH2 | Drug Info | [22] | |||
| 8 | Des-AA1,2,4,12,13-[D-Trp8]SRIF | Drug Info | [16] | |||
| 9 | Des-AA1,2,4,13-[D-Trp8]SRIF | Drug Info | [16] | |||
| 10 | Des-AA1,2,4,5,11,12,13-[D-Trp8]SRIF | Drug Info | [16] | |||
| 11 | Des-AA1,2,4,5,13-[D-Trp8]-SRIF | Drug Info | [16] | |||
| 12 | Des-AA1,2,4,5,6,12,13-[D-Trp8]SRIF | Drug Info | [16] | |||
| 13 | Des-AA1,2,4,5-[D-Trp8]SRIF | Drug Info | [16] | |||
| 14 | Des-AA1,2,5,12,13-[D-Trp8]SRIF | Drug Info | [16] | |||
| 15 | Des-AA1,2,5-[D-Trp8,Tyr11]SRIF | Drug Info | [23] | |||
| 16 | Des-AA5-[D-Trp8]SRIF | Drug Info | [23] | |||
| 17 | H-c[Cys-Phe-DTrp-Lys-Thr-Cys]-OH | Drug Info | [24] | |||
| 18 | H-D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 | Drug Info | [22] | |||
| 19 | H-D-Phe-c[Cys-Ala-D-Trp-Lys-Thr-Cys]-Thr-NH2 | Drug Info | [24] | |||
| 20 | H-DPhe-c[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-NH2 | Drug Info | [24] | |||
| 21 | Pyz11-D-Trp8-SRIF | Drug Info | [19] | |||
| 22 | Pyz6-D-Trp8-SRIF | Drug Info | [19] | |||
| 23 | SOMATOSTATIN | Drug Info | [22] | |||
| 24 | SRIF-28 | Drug Info | [27] | |||
| Agonist | [+] 6 Agonist drugs | + | ||||
| 1 | TBR-760 | Drug Info | [17] | |||
| 2 | CGP 23996 | Drug Info | [20] | |||
| 3 | L-054,522 | Drug Info | [25] | |||
| 4 | L-054852 | Drug Info | [4] | |||
| 5 | L-779,976 | Drug Info | [26] | |||
| 6 | SRIF-14 | Drug Info | [20] | |||
| Antagonist | [+] 1 Antagonist drugs | + | ||||
| 1 | 98mTc-CIM-ANT | Drug Info | [15] | |||
| 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 | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating Transcription Factors | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
| 1 | cAMP signaling pathway | |||||
| 2 | Neuroactive ligand-receptor interaction | |||||
| 3 | Gastric acid secretion | |||||
| 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 | [+] 6 WikiPathways | + | ||||
| 1 | SIDS Susceptibility Pathways | |||||
| 2 | GPCRs, Class A Rhodopsin-like | |||||
| 3 | Peptide GPCRs | |||||
| 4 | GPCR ligand binding | |||||
| 5 | GPCR downstream signaling | |||||
| 6 | GPCRs, Other | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Versatile conjugation of octreotide to dendrimers by cycloaddition ("click") chemistry to yield high-affinity multivalent cyclic Peptide dendrimers. Bioconjug Chem. 2009 Jul;20(7):1323-31. | |||||
| REF 2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020 | |||||
| REF 3 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019 | |||||
| REF 4 | Treatment strategies for acromegaly. Expert Opin Emerg Drugs. 2005 Nov;10(4):875-90. | |||||
| REF 5 | 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. (Ligand id: 2031). | |||||
| REF 6 | Pasireotide, a multi-somatostatin receptor ligand with potential efficacy for treatment of pituitary and neuroendocrine tumors. Drugs Today (Barc). 2013 Feb;49(2):89-103. | |||||
| REF 7 | 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. (Ligand id: 2055). | |||||
| REF 8 | Emerging drugs for complications of end-stage liver disease. Expert Opin Emerg Drugs. 2008 Mar;13(1):159-74. | |||||
| REF 9 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 10 | ClinicalTrials.gov (NCT02527993) Treatment of Hypoglycemia Following Gastric Bypass Surgery. | |||||
| REF 11 | ClinicalTrials.gov (NCT04335357) TBR-760 in Adult Patients With Non-Functioning Pituitary Adenomas. U.S. National Institutes of Health. | |||||
| REF 12 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 13 | The somatostatin analog 188Re-P2045 inhibits the growth of AR42J pancreatic tumor xenografts. J Nucl Med. 2014 Dec;55(12):2020-5. | |||||
| REF 14 | 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 15 | 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: 356). | |||||
| REF 16 | Somatostatin receptor 1 selective analogues: 3. Dicyclic peptides. J Med Chem. 2005 Jan 27;48(2):515-22. | |||||
| REF 17 | TBR-760, a Dopamine-Somatostatin Compound, Arrests Growth of Aggressive Nonfunctioning Pituitary Adenomas in Mice. Endocrinology. 2020 Aug 1;161(8):bqaa101. | |||||
| REF 18 | Role of somatostatin in the augmentation of hippocampal long-term potentiation by FR121196, a putative cognitive enhancer. Eur J Pharmacol. 1993 Sep 7;241(1):27-34. | |||||
| REF 19 | Replacement of Phe6, Phe7, and Phe11 of D-Trp8-somatostatin-14 with L-pyrazinylalanine. Predicted and observed effects on binding affinities at hSS... J Med Chem. 2005 Jun 16;48(12):4025-30. | |||||
| REF 20 | [125I][Tyr3]octreotide labels human somatostatin sst2 and sst5 receptors. Eur J Pharmacol. 1998 May 8;348(2-3):311-20. | |||||
| REF 21 | An adjustable release rate linking strategy for cytotoxin-peptide conjugates. Bioorg Med Chem Lett. 2003 Mar 10;13(5):799-803. | |||||
| REF 22 | 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 23 | Somatostatin receptor 1 selective analogues: 2. N(alpha)-Methylated scan. J Med Chem. 2005 Jan 27;48(2):507-14. | |||||
| REF 24 | Novel sst2-selective somatostatin agonists. Three-dimensional consensus structure by NMR. J Med Chem. 2006 Jul 27;49(15):4487-96. | |||||
| REF 25 | 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 26 | Rapid identification of subtype-selective agonists of the somatostatin receptor through combinatorial chemistry. Science. 1998 Oct 23;282(5389):737-40. | |||||
| REF 27 | 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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