Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTAE1BR)

• DTT Name: Somatostatin receptor type 4 (SSTR4)
• Synonyms: SSTR4; SS4R
• Gene Name: SSTR4
• DTT Type: Clinical trial target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: SSR4_HUMAN
• TTD ID: T62974
• Sequence:
  MSAPSTLPPGGEEGLGTAWPSAANASSAPAEAEEAVAGPGDARAAGMVAIQCIYALVCLV
  GLVGNALVIFVILRYAKMKTATNIYLLNLAVADELFMLSVPFVASSAALRHWPFGSVLCR
  AVLSVDGLNMFTSVFCLTVLSVDRYVAVVHPLRAATYRRPSVAKLINLGVWLASLLVTLP
  IAIFADTRPARGGQAVACNLQWPHPAWSAVFVVYTFLLGFLLPVLAIGLCYLLIVGKMRA
  VALRAGWQQRRRSEKKITRLVLMVVVVFVLCWMPFYVVQLLNLFVTSLDATVNHVSLILS
  YANSCANPILYGFLSDNFRRFFQRVLCLRCCLLEGAGGAEEEPLDYYATALKSKGGAGCM
  CPPLPCQQEALQPEPGRKRIPLTRTTTF
• Function: Receptor for somatostatin-14. The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. It is functionally coupled not only to inhibition of adenylate cyclase, but also to activation of both arachidonate release and mitogen-activated protein (MAP) kinase cascade. Mediates antiproliferative action of somatostatin in tumor cells.
• KEGG Pathway: 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

4 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	[1]
177Lu-DOTATATE	DMT8GVU	Hepatitis C virus infection	1E51.1	Phase 2	[2]
LY3556050	DMTW2XB	Chronic low-back pain	MG30	Phase 2	[3]
CNTX-0290	DMJPEVA	Chronic pain	MG30	Phase 1	[4]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
FR-121196	DMNRUGA	Alzheimer disease	8A20	Terminated	[5]

30 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	[6]
Ala11-SRIF-14-amide	DMZH4NQ	Discovery agent	N.A.	Investigative	[7]
Ala6-SRIF-14-amide	DM9RQ7E	Discovery agent	N.A.	Investigative	[7]
beta3-tetrapeptide	DMBAN5P	Discovery agent	N.A.	Investigative	[8]
CGP 23996	DMTECXA	Discovery agent	N.A.	Investigative	[9]
Cytotoxin Peptide Conjugate	DM7SVLZ	Discovery agent	N.A.	Investigative	[10]
D-Trp8-SRIF-14	DM1JL5W	Discovery agent	N.A.	Investigative	[7]
Des-AA1,2,4,12,13-[D-Trp8]SRIF	DMMWDC5	Discovery agent	N.A.	Investigative	[1]
Des-AA1,2,4,13-[D-Trp8]SRIF	DMR6Z2N	Discovery agent	N.A.	Investigative	[1]
Des-AA1,2,4,5,10,12,13-[D-Trp8]SRIF	DMEVOD2	Discovery agent	N.A.	Investigative	[1]
Des-AA1,2,4,5,13-[D-Trp8]-SRIF	DMYZXEO	Discovery agent	N.A.	Investigative	[1]
Des-AA1,2,4,5,6,12,13-[D-Trp8]SRIF	DM6HZ8D	Discovery agent	N.A.	Investigative	[1]
Des-AA1,2,4,5-[D-Trp8]SRIF	DMEN4G8	Discovery agent	N.A.	Investigative	[1]
Des-AA1,2,5,12,13-[D-Trp8,IAmp9]SRIF	DMZPXGY	Discovery agent	N.A.	Investigative	[1]
Des-AA1,2,5,12,13-[D-Trp8]SRIF	DM1KJAE	Discovery agent	N.A.	Investigative	[1]
Des-AA1,2,5-[D-Nal8,IAmp9,(NalphaMe)Thr12]SRIF	DMYFCB0	Discovery agent	N.A.	Investigative	[11]
Des-AA1,2,5-[D-Trp8,(NalphaMe)IAmp9]SRIF	DMX2I4P	Discovery agent	N.A.	Investigative	[11]
Des-AA1,2,5-[D-Trp8,Tyr11]SRIF	DM7MZ2V	Discovery agent	N.A.	Investigative	[11]
Des-AA1,2,5-[IAmp9,Tyr11]-SRIF	DMQRUF6	Discovery agent	N.A.	Investigative	[11]
Des-AA1,5-[Tyr2,D-Trp8,(NalphaMe)IAmp9]Cbm-SRIF	DMFCA05	Discovery agent	N.A.	Investigative	[11]
Des-AA1,5-[Tyr2,D-Trp8,(NalphaMe)IAmp9]SRIF	DMW56NI	Discovery agent	N.A.	Investigative	[11]
Des-AA5-[D-Trp8]SRIF	DMO3CFV	Discovery agent	N.A.	Investigative	[11]
L-803,087	DMWBRDK	Discovery agent	N.A.	Investigative	[12]
NNC269100	DMAQTW3	Discovery agent	N.A.	Investigative	[13]
Pyz11-D-Trp8-SRIF	DMFUYR1	Discovery agent	N.A.	Investigative	[7]
Pyz6-D-Trp8-SRIF	DMDB3Q8	Discovery agent	N.A.	Investigative	[7]
Pyz7-D-Trp8-SRIF	DM9D805	Discovery agent	N.A.	Investigative	[7]
SOMATOSTATIN	DMIOFQE	Acromegaly	5A60.0	Investigative	[14]
SRIF-14	DMDY1M7	Discovery agent	N.A.	Investigative	[15]
SRIF-28	DM0OM9L	Discovery agent	N.A.	Investigative	[16]

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	1.12E-02	-0.07	-0.32
Melanoma	2C82	Skin	4.74E-01	-0.08	-0.23

References

• [1] Somatostatin receptor 1 selective analogues: 3. Dicyclic peptides. J Med Chem. 2005 Jan 27;48(2):515-22.
• [2] New Drug in Development Shows Improved Progression-Free Survival for Patients with Advanced Metastatic Midgut Neuroendocrine Tumors
• [3] ClinicalTrials.gov (NCT04874636) Randomized, Placebo-Controlled, Phase 2 Clinical Trial to Evaluate LY3556050 for the Treatment of Chronic Low Back Pain. U.S.National Institutes of Health.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] 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.
• [6] 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: 358).
• [7] 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.
• [8] Beta(2)/beta(3)-di- and alpha/beta(3)-tetrapeptide derivatives as potent agonists at somatostatin sst(4) receptors. Naunyn Schmiedebergs Arch Pharmacol. 2003 Feb;367(2):95-103.
• [9] Characterisation of human recombinant somatostatin receptors. 1. Radioligand binding studies. Naunyn Schmiedebergs Arch Pharmacol. 1999 Nov;360(5):488-99.
• [10] An adjustable release rate linking strategy for cytotoxin-peptide conjugates. Bioorg Med Chem Lett. 2003 Mar 10;13(5):799-803.
• [11] Somatostatin receptor 1 selective analogues: 2. N(alpha)-Methylated scan. J Med Chem. 2005 Jan 27;48(2):507-14.
• [12] Rapid identification of subtype-selective agonists of the somatostatin receptor through combinatorial chemistry. Science. 1998 Oct 23;282(5389):737-40.
• [13] Nonpeptide somatostatin agonists with sst4 selectivity: synthesis and structure-activity relationships of thioureas. J Med Chem. 1998 Nov 19;41(24):4693-705.
• [14] 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.
• [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.
• [16] Novel octreotide dicarba-analogues with high affinity and different selectivity for somatostatin receptors. J Med Chem. 2010 Aug 26;53(16):6188-97.