Therapeutic Targets Database
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Target Validation Information
TTD IDTTDC00034
Target NameSomatostatin receptor type 4    
Type of TargetClinical trial target    
Drug Potency against TargetCAP-232IC50 = 0.1 nM[1]
Somatostatin AnalogueIC50 = 0.297 nM[2]
Somatostatin AnalogueIC50 = 0.308 nM[2]
Somatostatin AnalogueIC50 = 0.397 nM[2]
Somatostatin AnalogueIC50 = 0.498 nM[2]
Des-AA1,2,5-[D-Trp8,Tyr11]SRIFIC50 = 0.5 nM[3]
Des-AA1,2,5,12,13-[D-Trp8]SRIFIC50 = 0.6 nM[4]
Des-AA1,2,4,5,13-[D-Trp8]-SRIFIC50 = 1 nM[4]
Des-AA1,2,4,12,13-[D-Trp8]SRIFIC50 = 1.2 nM[4]
Des-AA1,2,4,13-[D-Trp8]SRIFIC50 = 1.4 nM[4]
SRIF-28IC50 = 1.6 nM[5]
Des-AA5-[D-Trp8]SRIFIC50 = 1.7 nM[3]
ODT-8IC50 = 1.8 nM[4]
Radiolabeled octreotide derivativeIC50 = 1033 nM[6]
CytotoxinPeptide ConjugateIC50 = 2.79 nM[7]
Des-AA1,2,5-[D-Trp8,(NalphaMe)IAmp9]SRIFIC50 = 226 nM[3]
Des-AA1,2,4,5,6,12,13-[D-Trp8]SRIFIC50 = 229 nM[4]
Des-AA1,5-[Tyr2,D-Trp8,(NalphaMe)IAmp9]SRIFIC50 = 245 nM[3]
Des-AA1,2,4,5-[D-Trp8]SRIFIC50 = 3.3 nM[4]
Radiolabeled octreotide derivativeIC50 = 300 nM[6]
Radiolabeled octreotide derivativeIC50 = 337 nM[6]
Radiolabeled octreotide derivativeIC50 = 346 nM[6]
Radiolabeled octreotide derivativeIC50 = 356 nM[6]
Des-AA1,2,5-[IAmp9,Tyr11]-SRIFIC50 = 384 nM[3]
Des-AA1,2,5-[D-Nal8,IAmp9,(NalphaMe)Thr12]SRIFIC50 = 417 nM[3]
Des-AA1,5-[Tyr2,D-Trp8,(NalphaMe)IAmp9]Cbm-SRIFIC50 = 418 nM[3]
Radiolabeled octreotide derivativeIC50 = 453 nM[6]
Radiolabeled octreotide derivativeIC50 = 482 nM[6]
Radiolabeled octreotide derivativeIC50 = 523 nM[6]
CytotoxinPeptide ConjugateIC50 = 54.2 nM[7]
CytotoxinPeptide ConjugateIC50 = 571 nM[7]
Radiolabeled octreotide derivativeIC50 = 729 nM[6]
Des-AA1,2,4,5,10,12,13-[D-Trp8]SRIFIC50 = 786 nM[4]
Radiolabeled octreotide derivativeIC50 = 797 nM[6]
Radiolabeled octreotide derivativeIC50 = 823 nM[6]
Radiolabeled octreotide derivativeIC50 = 837 nM[6]
Des-AA1,2,5,12,13-[D-Trp8,IAmp9]SRIFIC50 = 932 nM[4]
Ala11-SRIF-14-amideKi < 1 nM[8]
SOMATOSTATINKi = 1.7 nM[9]
Pyz11-D-Trp8-SRIFKi = 124 nM[8]
D-Trp8-SRIF-14Ki = 3.7 nM[8]
Pyz7-D-Trp8-SRIFKi = 700 nM[8]
Pyz6-D-Trp8-SRIFKi = 77 nM[8]
Ala6-SRIF-14-amideKi = 80 nM[8]
Action against Disease ModelTLN-4601TLN-4601 potently inhibited the anchorage-dependent and -independent growth of KRAS-transformed h uMan nestin-positive (HPNE) pancreatic duct-derived cells. The growth of KRAS mutation-positive pancreatic carcinoma cell lines (PDAC) was inhibited by TLN-4601.[10]
The Effect of Target Knockout, Knockdown or Genetic VariationsFunctional experiments revealed no differences in intestinal motility or smooth muscle cell contractility between wild-type and somatostatin (SOM) receptor 4(SSTR4) knockout (SSTR4(-/-)) mice in physiological conditions. As revealed by multiple immunofluorescent labellings, RT-PCR and quantitative real time RT-PCR (qPCR), genetic deficiency of SSTR4 considerably altered the expression of SOM and SSTRs in non-inflamed and inflamed conditions, affecting both extrinsic and intrinsic components of the intestinal innervation, along with SSTR expression in several non-neuronal cell types. Moreover, substance P and calcitonin gene-related peptide expression were significantly elevated in SSTR4(-/-) mice, confirming the modulatory role of SSTR4 on intestinal pro-inflammatory neuropeptide expression. These data suggest that SSTR4 plays a previously unexpected modulatory role in the regulation of intestinal SSTR expression. Moreover, in addition to the recently described inhibitory effects of SSTR4 on the neuronal release of pro-inflammatory peptides, SSTR4 appears also to be involved in the neuronal expression of both pro- and anti-inflammatory peptides in the murine small intestine[11]
Ref 1Comparison of the binding modes of TT-232 in somatostatin receptors type 1 and 4. Journal of Molecular Structure: THEOCHEM. Volume 816, Issues 1-3, 20 August 2007, Pages 73-76. To Reference
Ref 2J Med Chem. 1999 Apr 22;42(8):1341-7.Comparison of four 64Cu-labeled somatostatin analogues in vitro and in a tumor-bearing rat model: evaluation of new derivatives for positron emission tomography imaging and targeted radiotherapy. To Reference
Ref 3J Med Chem. 2005 Jan 27;48(2):507-14.Somatostatin receptor 1 selective analogues: 2. N(alpha)-Methylated scan. To Reference
Ref 4J Med Chem. 2005 Jan 27;48(2):515-22.Somatostatin receptor 1 selective analogues: 3. Dicyclic peptides. To Reference
Ref 5J Med Chem. 2010 Aug 26;53(16):6188-97.Novel octreotide dicarba-analogues with high affinity and different selectivity for somatostatin receptors. To Reference
Ref 6J 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. To Reference
Ref 7Bioorg Med Chem Lett. 2003 Mar 10;13(5):799-803.An adjustable release rate linking strategy for cytotoxin-peptide conjugates. To Reference
Ref 8J 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. To Reference
Ref 9J 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 pituitary cells. To Reference
Ref 10Cancer Chemother Pharmacol. 2008 May;61(6):911-21. Epub 2007 Jul 11.Identification, characterization and potent antitumor activity of ECO-4601, a novel peripheral benzodiazepine receptor ligand. To Reference
Ref 11J Cell Mol Med. 2009 Sep;13(9B):3283-95. Epub 2009 May 1.Effect of genetic SSTR4 ablation on inflammatory peptide and receptor expression in the non-inflamed and inflamed murine intestine. To Reference



 

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