Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTZ6T9E)

• DTT Name: Somatostatin receptor type 2 (SSTR2)
• Synonyms: Sst(2); Somatostatin receptor 2; SS2R; SS2-R; SS-2-R; SRIF-1
• Gene Name: SSTR2
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: SSR2_HUMAN
• TTD ID: T53024
• Sequence:
  MDMADEPLNGSHTWLSIPFDLNGSVVSTNTSNQTEPYYDLTSNAVLTFIYFVVCIIGLCG
  NTLVIYVILRYAKMKTITNIYILNLAIADELFMLGLPFLAMQVALVHWPFGKAICRVVMT
  VDGINQFTSIFCLTVMSIDRYLAVVHPIKSAKWRRPRTAKMITMAVWGVSLLVILPIMIY
  AGLRSNQWGRSSCTINWPGESGAWYTGFIIYTFILGFLVPLTIICLCYLFIIIKVKSSGI
  RVGSSKRKKSEKKVTRMVSIVVAVFIFCWLPFYIFNVSSVSMAISPTPALKGMFDFVVVL
  TYANSCANPILYAFLSDNFKKSFQNVLCLVKVSGTDDGERSDSKQDKSRLNETTETQRTL
  LNGDLQTSI
• 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.
• KEGG Pathway:
  cAMP signaling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Gastric acid secretion (hsa04971)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DTT

5 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Copper dotatate Cu-64	DM26KR1	Diagnostic imaging	N.A.	Approved	[2]
Ga-68-DOTATOC	DMZ0P95	Diagnostic imaging	N.A.	Approved	[3]
Lanreotide acetate	DMG6ZU4	Acromegaly	5A60.0	Approved	[4]
Octreotide	DMHIDCJ	Acromegaly	5A60.0	Approved	[1]
Pasireotide	DMHM7JS	Cushing disease	5A70	Approved	[5]

5 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ODT-8	DMBWO5T	N. A.	N. A.	Phase 3	[6]
Paltusotine	DM97IN2	Acromegaly	5A60.0	Phase 3	[7]
TBR-760	DMM5BVG	Pituitary adenoma	2F37.0	Phase 2	[8]
PEN-221	DMMAUOK	Neuroendocrine cancer	2B72.1	Phase 1/2	[9]
Re-188-P-2045	DM614BA	Lung cancer	2C25.0	Phase 1/2	[10]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
FR-121196	DMNRUGA	Alzheimer disease	8A20	Terminated	[11]

29 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
98mTc-CIM-ANT	DMJ1VAE	Neuroendocrine cancer	2B72.1	Investigative	[5]
99mTc-MIP-1407	DMYPD5L	Neuroendocrine cancer	2B72.1	Investigative	[5]
Ala11-SRIF-14-amide	DMZH4NQ	Discovery agent	N.A.	Investigative	[12]
Ala6-SRIF-14-amide	DM9RQ7E	Discovery agent	N.A.	Investigative	[12]
Ala7-SRIF-14-amide	DMWF8GN	Discovery agent	N.A.	Investigative	[12]
CGP 23996	DMTECXA	Discovery agent	N.A.	Investigative	[13]
Cytotoxin Peptide Conjugate	DM7SVLZ	Discovery agent	N.A.	Investigative	[14]
D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Asp-NH2	DM0YQHM	Discovery agent	N.A.	Investigative	[15]
Des-AA1,2,4,12,13-[D-Trp8]SRIF	DMMWDC5	Discovery agent	N.A.	Investigative	[6]
Des-AA1,2,4,13-[D-Trp8]SRIF	DMR6Z2N	Discovery agent	N.A.	Investigative	[6]
Des-AA1,2,4,5,11,12,13-[D-Trp8]SRIF	DMJI6BK	Discovery agent	N.A.	Investigative	[6]
Des-AA1,2,4,5,13-[D-Trp8]-SRIF	DMYZXEO	Discovery agent	N.A.	Investigative	[6]
Des-AA1,2,4,5,6,12,13-[D-Trp8]SRIF	DM6HZ8D	Discovery agent	N.A.	Investigative	[6]
Des-AA1,2,4,5-[D-Trp8]SRIF	DMEN4G8	Discovery agent	N.A.	Investigative	[6]
Des-AA1,2,5,12,13-[D-Trp8]SRIF	DM1KJAE	Discovery agent	N.A.	Investigative	[6]
Des-AA1,2,5-[D-Trp8,Tyr11]SRIF	DM7MZ2V	Discovery agent	N.A.	Investigative	[16]
Des-AA5-[D-Trp8]SRIF	DMO3CFV	Discovery agent	N.A.	Investigative	[16]
H-c[Cys-Phe-DTrp-Lys-Thr-Cys]-OH	DMCQH23	Discovery agent	N.A.	Investigative	[17]
H-D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2	DM1EGC3	Discovery agent	N.A.	Investigative	[15]
H-D-Phe-c[Cys-Ala-D-Trp-Lys-Thr-Cys]-Thr-NH2	DML8S7J	Discovery agent	N.A.	Investigative	[17]
H-DPhe-c[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-NH2	DMLCIZ8	Discovery agent	N.A.	Investigative	[17]
L-054,522	DMQR6ZX	Discovery agent	N.A.	Investigative	[18]
L-054852	DMXB7G5	Acromegaly	5A60.0	Investigative	[4]
L-779,976	DMMUAW5	Discovery agent	N.A.	Investigative	[19]
Pyz11-D-Trp8-SRIF	DMFUYR1	Discovery agent	N.A.	Investigative	[12]
Pyz6-D-Trp8-SRIF	DMDB3Q8	Discovery agent	N.A.	Investigative	[12]
SOMATOSTATIN	DMIOFQE	Acromegaly	5A60.0	Investigative	[15]
SRIF-14	DMDY1M7	Discovery agent	N.A.	Investigative	[13]
SRIF-28	DM0OM9L	Discovery agent	N.A.	Investigative	[20]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Lung cancer	2C82	Lung tissue	2.41E-05	0.05	0.21
Alzheimer's disease	8A00.0	Entorhinal cortex	9.79E-07	-0.38	-0.65
Melanoma	2C82	Skin	4.36E-01	0.22	0.28

References

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• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
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• [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. (Target id: 356).
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• [9] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [10] The somatostatin analog 188Re-P2045 inhibits the growth of AR42J pancreatic tumor xenografts. J Nucl Med. 2014 Dec;55(12):2020-5.
• [11] 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.
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• [13] [125I][Tyr3]octreotide labels human somatostatin sst2 and sst5 receptors. Eur J Pharmacol. 1998 May 8;348(2-3):311-20.
• [14] An adjustable release rate linking strategy for cytotoxin-peptide conjugates. Bioorg Med Chem Lett. 2003 Mar 10;13(5):799-803.
• [15] 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.
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