Target Information

Target General Infomation
Target ID
T53024
Former ID
TTDS00394
Target Name
Somatostatin receptor type 2
Gene Name
SSTR2
Synonyms
SRIF-1; SS2R; Somatostatin receptor 2; Sst(2); SSTR2
Target Type
Successful
Disease Acromegaly [ICD9: 253; ICD10: E22.0]
Alzheimer disease [ICD9: 331; ICD10: G30]
Cushing's disease [ICD9: 255; ICD10: E24.0]
Lung cancer [ICD9: 162; ICD10: C33-C34]
Neuroendocrine cancer [ICD10: C7A]
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.
BioChemical Class
GPCR rhodopsin
Target Validation
T53024
UniProt ID
P30874
Sequence
MDMADEPLNGSHTWLSIPFDLNGSVVSTNTSNQTEPYYDLTSNAVLTFIYFVVCIIGLCG
NTLVIYVILRYAKMKTITNIYILNLAIADELFMLGLPFLAMQVALVHWPFGKAICRVVMT
VDGINQFTSIFCLTVMSIDRYLAVVHPIKSAKWRRPRTAKMITMAVWGVSLLVILPIMIY
AGLRSNQWGRSSCTINWPGESGAWYTGFIIYTFILGFLVPLTIICLCYLFIIIKVKSSGI
RVGSSKRKKSEKKVTRMVSIVVAVFIFCWLPFYIFNVSSVSMAISPTPALKGMFDFVVVL
TYANSCANPILYAFLSDNFKKSFQNVLCLVKVSGTDDGERSDSKQDKSRLNETTETQRTL
LNGDLQTSI
Drugs and Mode of Action
Drug(s) Lanreotide acetate Drug Info Approved Acromegaly [532253], [539302]
Lanreotide Autogel Drug Info Approved Acromegaly [536151]
Octreotide Drug Info Approved Acromegaly [536650], [539309]
Pasireotide Drug Info Approved Cushing's disease [525297], [551871]
ODT-8 Drug Info Phase 3 Discovery agent [523209]
Re-188-P-2045 Drug Info Phase 1/2 Lung cancer [533014]
FR-121196 Drug Info Terminated Alzheimer disease [544870]
Antagonist 98mTC-CIM-ANT Drug Info [543788]
Modulator 99mTc-MIP-1407 Drug Info [543788]
FR-121196 Drug Info [533791]
Lanreotide acetate Drug Info [532253]
Re-188-P-2045 Drug Info [533014]
Inhibitor Ala11-SRIF-14-amide Drug Info [527585]
Ala6-SRIF-14-amide Drug Info [527585]
Ala7-SRIF-14-amide Drug Info [527585]
CytotoxinPeptide Conjugate Drug Info [526564]
D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Asp-NH2 Drug Info [527802]
Des-AA1,2,4,12,13-[D-Trp8]SRIF Drug Info [527385]
Des-AA1,2,4,13-[D-Trp8]SRIF Drug Info [527385]
Des-AA1,2,4,5,11,12,13-[D-Trp8]SRIF Drug Info [527385]
Des-AA1,2,4,5,13-[D-Trp8]-SRIF Drug Info [527385]
Des-AA1,2,4,5,6,12,13-[D-Trp8]SRIF Drug Info [527385]
Des-AA1,2,4,5-[D-Trp8]SRIF Drug Info [527385]
Des-AA1,2,5,12,13-[D-Trp8]SRIF Drug Info [527385]
Des-AA1,2,5-[D-Trp8,Tyr11]SRIF Drug Info [527384]
Des-AA5-[D-Trp8]SRIF Drug Info [527384]
H-c[Cys-Phe-DTrp-Lys-Thr-Cys]-OH Drug Info [528320]
H-D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 Drug Info [527802]
H-D-Phe-c[Cys-Ala-D-Trp-Lys-Thr-Cys]-Thr-NH2 Drug Info [528320]
H-DPhe-c[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-NH2 Drug Info [528320]
ODT-8 Drug Info [527385]
Pasireotide Drug Info [543788]
Pyz11-D-Trp8-SRIF Drug Info [527585]
Pyz6-D-Trp8-SRIF Drug Info [527585]
Radiolabeled octreotide derivative Drug Info [527508]
SOMATOSTATIN Drug Info [527802]
SRIF-28 Drug Info [531062]
Agonist CGP 23996 Drug Info [534665]
L-054,522 Drug Info [534701]
L-054852 Drug Info [536151]
L-779,976 Drug Info [534729]
SRIF-14 Drug Info [534665]
Binder Lanreotide Autogel Drug Info [536151]
Octreotide Drug Info [537489]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway cAMP signaling pathway
Neuroactive ligand-receptor interaction
Gastric acid secretion
PANTHER Pathway Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway
Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway
Reactome Peptide ligand-binding receptors
G alpha (i) signalling events
WikiPathways SIDS Susceptibility Pathways
GPCRs, Class A Rhodopsin-like
Peptide GPCRs
GPCR ligand binding
GPCR downstream signaling
GPCRs, Other
References
Ref 523209ClinicalTrials.gov (NCT01220167) Three-way Crossover Comparative Water-effect Bioavailability to Compare Ondansetron ODFS 8mg With and Without Water With Zofran ODT 8mg Without Water in 18 Healthy Participants Under Fasting Conditions. U.S. National Institutes of Health.
Ref 525297ClinicalTrials.gov (NCT02527993) Treatment of Hypoglycemia Following Gastric Bypass Surgery.
Ref 532253Pasireotide, 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 533014The somatostatin analog 188Re-P2045 inhibits the growth of AR42J pancreatic tumor xenografts. J Nucl Med. 2014 Dec;55(12):2020-5.
Ref 536151Treatment strategies for acromegaly. Expert Opin Emerg Drugs. 2005 Nov;10(4):875-90.
Ref 536650Emerging drugs for complications of end-stage liver disease. Expert Opin Emerg Drugs. 2008 Mar;13(1):159-74.
Ref 539302(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 539309(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 544870Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001380)
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 526564Bioorg Med Chem Lett. 2003 Mar 10;13(5):799-803.An adjustable release rate linking strategy for cytotoxin-peptide conjugates.
Ref 527384J Med Chem. 2005 Jan 27;48(2):507-14.Somatostatin receptor 1 selective analogues: 2. N(alpha)-Methylated scan.
Ref 527385J Med Chem. 2005 Jan 27;48(2):515-22.Somatostatin receptor 1 selective analogues: 3. Dicyclic peptides.
Ref 527508J Med Chem. 2005 Apr 21;48(8):2778-89.N-terminal sugar conjugation and C-terminal Thr-for-Thr(ol) exchange in radioiodinated Tyr3-octreotide: effect on cellular ligand trafficking in vitro and tumor accumulation in vivo.
Ref 527585J Med Chem. 2005 Jun 16;48(12):4025-30.Replacement of Phe6, Phe7, and Phe11 of D-Trp8-somatostatin-14 with L-pyrazinylalanine. Predicted and observed effects on binding affinities at hSST2 and hSST4.An unexpected effect of the chirality of Trp8 on NMR spectra in methanol.
Ref 527802J Med Chem. 2005 Oct 20;48(21):6643-52.Discovery of iodinated somatostatin analogues selective for hsst2 and hsst5 with excellent inhibition of growth hormone and prolactin release from rat pituitarycells.
Ref 528320J Med Chem. 2006 Jul 27;49(15):4487-96.Novel sst2-selective somatostatin agonists. Three-dimensional consensus structure by NMR.
Ref 531062J Med Chem. 2010 Aug 26;53(16):6188-97.Novel octreotide dicarba-analogues with high affinity and different selectivity for somatostatin receptors.
Ref 532253Pasireotide, 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 533014The somatostatin analog 188Re-P2045 inhibits the growth of AR42J pancreatic tumor xenografts. J Nucl Med. 2014 Dec;55(12):2020-5.
Ref 533791Role 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 534665[125I][Tyr3]octreotide labels human somatostatin sst2 and sst5 receptors. Eur J Pharmacol. 1998 May 8;348(2-3):311-20.
Ref 534701Synthesis 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 534729Rapid identification of subtype-selective agonists of the somatostatin receptor through combinatorial chemistry. Science. 1998 Oct 23;282(5389):737-40.
Ref 536151Treatment strategies for acromegaly. Expert Opin Emerg Drugs. 2005 Nov;10(4):875-90.
Ref 537489Versatile 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 543788(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).

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