Target Information

Target General Infomation
Target ID
T62974
Former ID
TTDC00034
Target Name
Somatostatin receptor type 4
Gene Name
SSTR4
Synonyms
SS4R; SSTR4
Target Type
Clinical Trial
Disease Alzheimer disease [ICD9: 331; ICD10: G30]
HCV infection [ICD9: 070.4, 070.5, 070.70; ICD10: B17.1, B18.2]
Neuroendocrine cancer [ICD10: C7A]
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.
BioChemical Class
GPCR rhodopsin
Target Validation
T62974
UniProt ID
P31391
Sequence
MSAPSTLPPGGEEGLGTAWPSAANASSAPAEAEEAVAGPGDARAAGMVAIQCIYALVCLV
GLVGNALVIFVILRYAKMKTATNIYLLNLAVADELFMLSVPFVASSAALRHWPFGSVLCR
AVLSVDGLNMFTSVFCLTVLSVDRYVAVVHPLRAATYRRPSVAKLINLGVWLASLLVTLP
IAIFADTRPARGGQAVACNLQWPHPAWSAVFVVYTFLLGFLLPVLAIGLCYLLIVGKMRA
VALRAGWQQRRRSEKKITRLVLMVVVVFVLCWMPFYVVQLLNLFVTSLDATVNHVSLILS
YANSCANPILYGFLSDNFRRFFQRVLCLRCCLLEGAGGAEEEPLDYYATALKSKGGAGCM
CPPLPCQQEALQPEPGRKRIPLTRTTTF
Drugs and Mode of Action
Drug(s) ODT-8 Drug Info Phase 3 Discovery agent [523209]
177Lu-DOTATATE Drug Info Phase 2 HCV infection [524302]
FR-121196 Drug Info Terminated Alzheimer disease [544870]
Inhibitor 177Lu-DOTATATE Drug Info [1725888]
Ala11-SRIF-14-amide Drug Info [527585]
Ala6-SRIF-14-amide Drug Info [527585]
CytotoxinPeptide Conjugate Drug Info [526564]
D-Trp8-SRIF-14 Drug Info [527585]
Des-AA1,2,4,12,13-[D-Trp8]SRIF Drug Info [527385]
Des-AA1,2,4,13-[D-Trp8]SRIF Drug Info [527385]
Des-AA1,2,4,5,10,12,13-[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,IAmp9]SRIF Drug Info [527385]
Des-AA1,2,5,12,13-[D-Trp8]SRIF Drug Info [527385]
Des-AA1,2,5-[D-Nal8,IAmp9,(NalphaMe)Thr12]SRIF Drug Info [527384]
Des-AA1,2,5-[D-Trp8,(NalphaMe)IAmp9]SRIF Drug Info [527384]
Des-AA1,2,5-[D-Trp8,Tyr11]SRIF Drug Info [527384]
Des-AA1,2,5-[IAmp9,Tyr11]-SRIF Drug Info [527384]
Des-AA1,5-[Tyr2,D-Trp8,(NalphaMe)IAmp9]Cbm-SRIF Drug Info [527384]
Des-AA1,5-[Tyr2,D-Trp8,(NalphaMe)IAmp9]SRIF Drug Info [527384]
Des-AA5-[D-Trp8]SRIF Drug Info [527384]
ODT-8 Drug Info [527385]
Pyz11-D-Trp8-SRIF Drug Info [527585]
Pyz6-D-Trp8-SRIF Drug Info [527585]
Pyz7-D-Trp8-SRIF Drug Info [527585]
Radiolabeled octreotide derivative Drug Info [527508]
SOMATOSTATIN Drug Info [527802]
SRIF-28 Drug Info [531062]
Modulator 99mTc-MIP-1407 Drug Info [543790]
FR-121196 Drug Info [533791]
Agonist beta3-tetrapeptide Drug Info [526548]
CGP 23996 Drug Info [525652]
L-803,087 Drug Info [534729]
NNC269100 Drug Info [534752]
SRIF-14 Drug Info [534701]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Neuroactive ligand-receptor interaction
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
PathWhiz Pathway Gastric Acid Production
Reactome Peptide ligand-binding receptors
G alpha (i) signalling events
WikiPathways GPCRs, Class A Rhodopsin-like
Peptide GPCRs
GPCR ligand binding
GPCR downstream signaling
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 524302ClinicalTrials.gov (NCT01860742) Randomized Phase III of PRRT Versus Interferon. U.S. National Institutes of Health.
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 525652Characterisation of human recombinant somatostatin receptors. 1. Radioligand binding studies. Naunyn Schmiedebergs Arch Pharmacol. 1999 Nov;360(5):488-99.
Ref 526548Beta(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. Epub 2003 Jan 24.
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 531062J Med Chem. 2010 Aug 26;53(16):6188-97.Novel octreotide dicarba-analogues with high affinity and different selectivity for somatostatin receptors.
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 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 534752Nonpeptide somatostatin agonists with sst4 selectivity: synthesis and structure-activity relationships of thioureas. J Med Chem. 1998 Nov 19;41(24):4693-705.
Ref 543790(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).
Ref 1725888New Drug in Development Shows Improved Progression-Free Survival for Patients with Advanced Metastatic Midgut Neuroendocrine Tumors

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