Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTIND6G)

• DTT Name: Somatostatin receptor type 1 (SSTR1)
• Synonyms: Sst(1); Somatostatin receptor 1; SSTR1; SS1R; SRIF-2
• Gene Name: SSTR1
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: SSR1_HUMAN
• TTD ID: T16633
• Sequence:
  MFPNGTASSPSSSPSPSPGSCGEGGGSRGPGAGAADGMEEPGRNASQNGTLSEGQGSAIL
  ISFIYSVVCLVGLCGNSMVIYVILRYAKMKTATNIYILNLAIADELLMLSVPFLVTSTLL
  RHWPFGALLCRLVLSVDAVNMFTSIYCLTVLSVDRYVAVVHPIKAARYRRPTVAKVVNLG
  VWVLSLLVILPIVVFSRTAANSDGTVACNMLMPEPAQRWLVGFVLYTFLMGFLLPVGAIC
  LCYVLIIAKMRMVALKAGWQQRKRSERKITLMVMMVVMVFVICWMPFYVVQLVNVFAEQD
  DATVSQLSVILGYANSCANPILYGFLSDNFKRSFQRILCLSWMDNAAEEPVDYYATALKS
  RAYSVEDFQPENLESGGVFRNGTCTSRITTL
• 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.
• KEGG Pathway:
  cAMP signaling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lutetium Lu 177 dotatate	DMN1XVC	Neuroendocrine cancer	2B72.1	Approved	[2]
Pasireotide	DMHM7JS	Cushing disease	5A70	Approved	[1]

1 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	[3]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
FR-121196	DMNRUGA	Alzheimer disease	8A20	Terminated	[4]

42 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
99mTc-MIP-1407	DMYPD5L	Neuroendocrine cancer	2B72.1	Investigative	[4]
CGP 23996	DMTECXA	Discovery agent	N.A.	Investigative	[5]
Cytotoxin Peptide Conjugate	DM7SVLZ	Discovery agent	N.A.	Investigative	[6]
Des-AA1,2,4,12,13-[D-Trp8]SRIF	DMMWDC5	Discovery agent	N.A.	Investigative	[3]
Des-AA1,2,4,13-[D-Trp8]SRIF	DMR6Z2N	Discovery agent	N.A.	Investigative	[3]
Des-AA1,2,4,5,13-[D-Trp8]-SRIF	DMYZXEO	Discovery agent	N.A.	Investigative	[3]
Des-AA1,2,4,5-[D-Trp8]SRIF	DMEN4G8	Discovery agent	N.A.	Investigative	[3]
Des-AA1,2,5,12,13-[D-Trp8,IAmp9]SRIF	DMZPXGY	Discovery agent	N.A.	Investigative	[3]
Des-AA1,2,5,12,13-[D-Trp8]SRIF	DM1KJAE	Discovery agent	N.A.	Investigative	[3]
Des-AA1,2,5-[(NalphaMe)Cys3,D-Nal8,IAmp9]SRIF	DMVYHGI	Discovery agent	N.A.	Investigative	[7]
Des-AA1,2,5-[(NalphaMe)Cys3,D-Trp8,IAmp9]SRIF	DMY6NID	Discovery agent	N.A.	Investigative	[7]
Des-AA1,2,5-[(NalphaMe)D-Nal8,IAmp9]SRIF	DMQPVGO	Discovery agent	N.A.	Investigative	[7]
Des-AA1,2,5-[(NalphaMe)Lys4,D-Nal8,IAmp9]SRIF	DM478XZ	Discovery agent	N.A.	Investigative	[7]
Des-AA1,2,5-[D-Nal8,(NalphaMe)IAmp9,Tyr11]SRIF	DMQOL73	Discovery agent	N.A.	Investigative	[7]
Des-AA1,2,5-[D-Nal8,(NalphaMe)IAmp9]SRIF	DMN4ZYO	Discovery agent	N.A.	Investigative	[7]
Des-AA1,2,5-[D-Nal8,IAmp9,(NalphaMe)Cys14]SRIF	DMXD60K	Discovery agent	N.A.	Investigative	[7]
Des-AA1,2,5-[D-Nal8,IAmp9,(NalphaMe)Phe11]SRIF	DM0574W	Discovery agent	N.A.	Investigative	[7]
Des-AA1,2,5-[D-Nal8,IAmp9,(NalphaMe)Ser13]SRIF	DMOZ9WC	Discovery agent	N.A.	Investigative	[7]
Des-AA1,2,5-[D-Nal8,IAmp9,(NalphaMe)Thr12]SRIF	DMYFCB0	Discovery agent	N.A.	Investigative	[7]
Des-AA1,2,5-[D-Nal8,IAmp9]SRIF	DM6JAFM	Discovery agent	N.A.	Investigative	[7]
Des-AA1,2,5-[D-Trp8,(NalphaMe)IAmp9,Tyr11]SRIF	DMLHUPY	Discovery agent	N.A.	Investigative	[7]
Des-AA1,2,5-[D-Trp8,(NalphaMe)IAmp9]SRIF	DMX2I4P	Discovery agent	N.A.	Investigative	[7]
Des-AA1,2,5-[D-Trp8,IAmp9,(NalphaMe)Cys14]SRIF	DMFXKRO	Discovery agent	N.A.	Investigative	[7]
Des-AA1,2,5-[D-Trp8,IAmp9,(NalphaMe)Ser13]SRIF	DM9EN01	Discovery agent	N.A.	Investigative	[7]
Des-AA1,2,5-[D-Trp8,IAmp9,(NalphaMe)Thr12]SRIF	DMB10GV	Discovery agent	N.A.	Investigative	[7]
Des-AA1,2,5-[D-Trp8,IAmp9,m-I-Tyr11]Cbm-SRIF	DMH0DLZ	Discovery agent	N.A.	Investigative	[7]
Des-AA1,2,5-[D-Trp8,IAmp9,Tyr11]Cbm-SRIF	DMXWF2Z	Discovery agent	N.A.	Investigative	[7]
Des-AA1,2,5-[D-Trp8,IAmp9]SRIF CH-275	DMSXILZ	Discovery agent	N.A.	Investigative	[7]
Des-AA1,2,5-[D-Trp8,Tyr11]SRIF	DM7MZ2V	Discovery agent	N.A.	Investigative	[7]
Des-AA1,2,5-[IAmp9,Tyr11]-SRIF	DMQRUF6	Discovery agent	N.A.	Investigative	[7]
Des-AA1,4,5,13-[Tyr2,D-Trp8]-SRIF	DMPMAXI	Discovery agent	N.A.	Investigative	[3]
Des-AA1,5-[Tyr2,D-Trp8,(NalphaMe)IAmp9]Cbm-SRIF	DMFCA05	Discovery agent	N.A.	Investigative	[7]
Des-AA1,5-[Tyr2,D-Trp8,(NalphaMe)IAmp9]SRIF	DMW56NI	Discovery agent	N.A.	Investigative	[7]
Des-AA1,5-[Tyr2,D-Trp8,IAmp9]Cbm-SRIF	DMV8EWF	Discovery agent	N.A.	Investigative	[7]
Des-AA1,5-[Tyr2,D-Trp8,IAmp9]SRIF CH-288	DMLY7DC	Discovery agent	N.A.	Investigative	[3]
Des-AA5-[D-Trp8]SRIF	DMO3CFV	Discovery agent	N.A.	Investigative	[7]
L-797,591	DM96ASN	Discovery agent	N.A.	Investigative	[8]
L-817,818	DM8YT7X	Discovery agent	N.A.	Investigative	[8]
SOMATOSTATIN	DMIOFQE	Acromegaly	5A60.0	Investigative	[9]
SRA880	DM37YJH	Discovery agent	N.A.	Investigative	[10]
SRIF-14	DMDY1M7	Discovery agent	N.A.	Investigative	[11]
SRIF-28	DM0OM9L	Discovery agent	N.A.	Investigative	[12]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Alzheimer's disease	8A00.0	Entorhinal cortex	2.39E-14	-0.6	-0.83
Melanoma	2C82	Skin	3.82E-04	-1.07	-1.37

References

• [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).
• [2] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [3] Somatostatin receptor 1 selective analogues: 3. Dicyclic peptides. J Med Chem. 2005 Jan 27;48(2):515-22.
• [4] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [5] Characterisation of human recombinant somatostatin receptors. 1. Radioligand binding studies. Naunyn Schmiedebergs Arch Pharmacol. 1999 Nov;360(5):488-99.
• [6] An adjustable release rate linking strategy for cytotoxin-peptide conjugates. Bioorg Med Chem Lett. 2003 Mar 10;13(5):799-803.
• [7] Somatostatin receptor 1 selective analogues: 2. N(alpha)-Methylated scan. J Med Chem. 2005 Jan 27;48(2):507-14.
• [8] Rapid identification of subtype-selective agonists of the somatostatin receptor through combinatorial chemistry. Science. 1998 Oct 23;282(5389):737-40.
• [9] 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.
• [10] SRA880, in vitro characterization of the first non-peptide somatostatin sst(1) receptor antagonist. Neurosci Lett. 2004 May 6;361(1-3):132-5.
• [11] 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.
• [12] Novel octreotide dicarba-analogues with high affinity and different selectivity for somatostatin receptors. J Med Chem. 2010 Aug 26;53(16):6188-97.