Target Information
| Target General Information | Top | |||||
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| Target ID |
T62974
(Former ID: TTDC00034)
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| Target Name |
Somatostatin receptor type 4 (SSTR4)
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| Synonyms |
SSTR4; SS4R
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| Gene Name |
SSTR4
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Hepatitis virus infection [ICD-11: 1E50-1E51] | |||||
| 2 | Chronic pain [ICD-11: MG30] | |||||
| 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.
Click to Show/Hide
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MSAPSTLPPGGEEGLGTAWPSAANASSAPAEAEEAVAGPGDARAAGMVAIQCIYALVCLV
GLVGNALVIFVILRYAKMKTATNIYLLNLAVADELFMLSVPFVASSAALRHWPFGSVLCR AVLSVDGLNMFTSVFCLTVLSVDRYVAVVHPLRAATYRRPSVAKLINLGVWLASLLVTLP IAIFADTRPARGGQAVACNLQWPHPAWSAVFVVYTFLLGFLLPVLAIGLCYLLIVGKMRA VALRAGWQQRRRSEKKITRLVLMVVVVFVLCWMPFYVVQLLNLFVTSLDATVNHVSLILS YANSCANPILYGFLSDNFRRFFQRVLCLRCCLLEGAGGAEEEPLDYYATALKSKGGAGCM CPPLPCQQEALQPEPGRKRIPLTRTTTF Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | 177Lu-DOTATATE | Drug Info | Phase 2 | Hepatitis C virus infection | [2] | |
| 2 | CNTX-0290 | Drug Info | Phase 1 | Chronic pain | [3] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | FR-121196 | Drug Info | Terminated | Alzheimer disease | [4] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Inhibitor | [+] 26 Inhibitor drugs | + | ||||
| 1 | ODT-8 | Drug Info | [1] | |||
| 2 | 177Lu-DOTATATE | Drug Info | [5] | |||
| 3 | Ala11-SRIF-14-amide | Drug Info | [8] | |||
| 4 | Ala6-SRIF-14-amide | Drug Info | [8] | |||
| 5 | Cytotoxin Peptide Conjugate | Drug Info | [11] | |||
| 6 | D-Trp8-SRIF-14 | Drug Info | [8] | |||
| 7 | Des-AA1,2,4,12,13-[D-Trp8]SRIF | Drug Info | [1] | |||
| 8 | Des-AA1,2,4,13-[D-Trp8]SRIF | Drug Info | [1] | |||
| 9 | Des-AA1,2,4,5,10,12,13-[D-Trp8]SRIF | Drug Info | [1] | |||
| 10 | Des-AA1,2,4,5,13-[D-Trp8]-SRIF | Drug Info | [1] | |||
| 11 | Des-AA1,2,4,5,6,12,13-[D-Trp8]SRIF | Drug Info | [1] | |||
| 12 | Des-AA1,2,4,5-[D-Trp8]SRIF | Drug Info | [1] | |||
| 13 | Des-AA1,2,5,12,13-[D-Trp8,IAmp9]SRIF | Drug Info | [1] | |||
| 14 | Des-AA1,2,5,12,13-[D-Trp8]SRIF | Drug Info | [1] | |||
| 15 | Des-AA1,2,5-[D-Nal8,IAmp9,(NalphaMe)Thr12]SRIF | Drug Info | [12] | |||
| 16 | Des-AA1,2,5-[D-Trp8,(NalphaMe)IAmp9]SRIF | Drug Info | [12] | |||
| 17 | Des-AA1,2,5-[D-Trp8,Tyr11]SRIF | Drug Info | [12] | |||
| 18 | Des-AA1,2,5-[IAmp9,Tyr11]-SRIF | Drug Info | [12] | |||
| 19 | Des-AA1,5-[Tyr2,D-Trp8,(NalphaMe)IAmp9]Cbm-SRIF | Drug Info | [12] | |||
| 20 | Des-AA1,5-[Tyr2,D-Trp8,(NalphaMe)IAmp9]SRIF | Drug Info | [12] | |||
| 21 | Des-AA5-[D-Trp8]SRIF | Drug Info | [12] | |||
| 22 | Pyz11-D-Trp8-SRIF | Drug Info | [8] | |||
| 23 | Pyz6-D-Trp8-SRIF | Drug Info | [8] | |||
| 24 | Pyz7-D-Trp8-SRIF | Drug Info | [8] | |||
| 25 | SOMATOSTATIN | Drug Info | [15] | |||
| 26 | SRIF-28 | Drug Info | [17] | |||
| Agonist | [+] 6 Agonist drugs | + | ||||
| 1 | CNTX-0290 | Drug Info | [3] | |||
| 2 | beta3-tetrapeptide | Drug Info | [9] | |||
| 3 | CGP 23996 | Drug Info | [10] | |||
| 4 | L-803,087 | Drug Info | [13] | |||
| 5 | NNC269100 | Drug Info | [14] | |||
| 6 | SRIF-14 | Drug Info | [16] | |||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | FR-121196 | Drug Info | [6] | |||
| 2 | 99mTc-MIP-1407 | Drug Info | [7] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Neuroactive ligand-receptor interaction | |||||
| Panther Pathway | [+] 2 Panther Pathways | + | ||||
| 1 | Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway | |||||
| 2 | Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Gastric Acid Production | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Peptide ligand-binding receptors | |||||
| 2 | G alpha (i) signalling events | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | GPCRs, Class A Rhodopsin-like | |||||
| 2 | Peptide GPCRs | |||||
| 3 | GPCR ligand binding | |||||
| 4 | GPCR downstream signaling | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Somatostatin receptor 1 selective analogues: 3. Dicyclic peptides. J Med Chem. 2005 Jan 27;48(2):515-22. | |||||
| REF 2 | ClinicalTrials.gov (NCT01860742) Randomized Phase III of PRRT Versus Interferon. U.S. National Institutes of Health. | |||||
| REF 3 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 4 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001380) | |||||
| REF 5 | New Drug in Development Shows Improved Progression-Free Survival for Patients with Advanced Metastatic Midgut Neuroendocrine Tumors | |||||
| REF 6 | 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. | |||||
| REF 7 | 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). | |||||
| REF 8 | 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. | |||||
| REF 9 | 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. | |||||
| REF 10 | Characterisation of human recombinant somatostatin receptors. 1. Radioligand binding studies. Naunyn Schmiedebergs Arch Pharmacol. 1999 Nov;360(5):488-99. | |||||
| REF 11 | An adjustable release rate linking strategy for cytotoxin-peptide conjugates. Bioorg Med Chem Lett. 2003 Mar 10;13(5):799-803. | |||||
| REF 12 | Somatostatin receptor 1 selective analogues: 2. N(alpha)-Methylated scan. J Med Chem. 2005 Jan 27;48(2):507-14. | |||||
| REF 13 | Rapid identification of subtype-selective agonists of the somatostatin receptor through combinatorial chemistry. Science. 1998 Oct 23;282(5389):737-40. | |||||
| REF 14 | Nonpeptide somatostatin agonists with sst4 selectivity: synthesis and structure-activity relationships of thioureas. J Med Chem. 1998 Nov 19;41(24):4693-705. | |||||
| REF 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. | |||||
| REF 16 | 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. | |||||
| REF 17 | Novel octreotide dicarba-analogues with high affinity and different selectivity for somatostatin receptors. J Med Chem. 2010 Aug 26;53(16):6188-97. | |||||
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