Therapeutic Targets Database
BIDD Pharmainformatics Databases


Target Validation Information
Target NameGrowth hormone secretagogue receptor type 1    
Type of TargetClinical trial target    
Drug Potency against TargetTZP-101EC50 = 29 nM[1]
RwFwLL-NH2IC50 = 12 nM[2]
QwFwLL-NH2IC50 = 120 nM[2]
AwFwLL-NH2IC50 = 15 nM[2]
DprwFwLL-NH2IC50 = 210 nM[2]
GHRELINIC50 = 250 nM[3]
rPKPfQwFwLL-NH2IC50 = 3.2 nM[2]
CP-424391-18IC50 = 3000 nM[4]
KwFwLL-NH2IC50 = 32 nM[2]
4-(3-hexylureido)-N-phenylbenzenesulfonamideIC50 = 4300 nM[5]
wFwLL-NH2IC50 = 530 nM[2]
wFwGG-NH2IC50 = 540 nM[2]
HwFwLL-NH2IC50 = 58 nM[2]
DwFwLL-NH2IC50 = 60 nM[2]
Action against Disease ModelTZP-101Previously we have shown in a rodent model of postoperative ileus that the synthetic ghrelin receptor agonist TZP-101 prevents the delay in gastric emptying and improves small intestinal transit. The goal of the present study was to investigate whether TZP-101 affects colonic transit and food intake in rats with postoperative ileus. TZP-101 (0.03-1 mg/kg) dose-dependently decreased the time to first bowel movement and increased fecal pellet output measured at 12 h and 24 h post-surgery compared to the vehicle. The administration of TZP-101 was not associated with a significant alteration in food intake.[6]
The Effect of Target Knockout, Knockdown or Genetic VariationsThe present study examined the role of ghrelin in producing normal metabolic and neurochemical responses to chronic stress. This was achieved by examining these responses in mice with targeted deletions of the ghrelin receptor gene (GHSR KO mice), and comparing them with the same responses in their wild-type (WT) littermates. As expected, WT stressed mice decreased their caloric intake, body weight gain and caloric efficiency while maintaining adiposity. GHSR KO mice, however, did not show these alterations despite having normal glucocorticoid responses to stress. In parallel with these changes, chronic unpredictable stress caused changes in norepinephrine, dopamine and serotonin in a n uMber of brain regions. Of these, norepinephrine neurotransmission in the arcuate nucleus and prefrontal cortex was differentially altered in GHSR KO mice. Within the nucleus ac uMbens, dopamine utilization was increased in WT mice but not in GHSR KO mice. Finally, there were strain differences in serotonin neurotransmission that may explain interstrain body weight and adiposity differences. These results suggest that the metabolic changes necessary to deal with the energetic challenge presented by repeated exposure to stressors do not occur in GHSR KO mice, and they are discussed within the context of the potential vulnerability to stress-induced pathology[7]
Ref 1Endocrinology. 2008 Dec;149(12):6280-8. Epub 2008 Aug 21.Pharmacological demarcation of the growth hormone, gut motility and feeding effects of ghrelin using a novel ghrelin receptor agonist. To Reference
Ref 2J Biol Chem. 2007 May 25;282(21):15799-811. Epub 2007 Mar 19.Identification of an efficacy switch region in the ghrelin receptor responsible for interchange between agonism and inverse agonism. To Reference
Ref 3J Med Chem. 2009 Apr 23;52(8):2196-203.Fluorine and rhenium substituted ghrelin analogues as potential imaging probes for the growth hormone secretagogue receptor. To Reference
Ref 4Bioorg Med Chem Lett. 2000 Jan 3;10(1):5-8.Modeling directed design and biological evaluation of quinazolinones as non-peptidic growth hormone secretagogues. To Reference
Ref 5Bioorg Med Chem Lett. 2009 Nov 1;19(21):6237-40. Epub 2009 Aug 26.Discovery and optimization of novel 4-[(aminocarbonyl)amino]-N-[4-(2-aminoethyl)phenyl]benzenesulfonamide ghrelin receptor antagonists. To Reference
Ref 6Eur J Pharmacol. 2009 Feb 14;604(1-3):132-7. Epub 2008 Dec 14.Effect of the ghrelin receptor agonist TZP-101 on colonic transit in a rat model of postoperative ileus. To Reference
Ref 7Eur J Neurosci. 2010 Aug;32(4):632-9. Epub 2010 Jun 30.Altered metabolic and neurochemical responses to chronic unpredictable stressors in ghrelin receptor-deficient mice. To Reference


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