Target Information

Target General Infomation
Target ID
T59604
Former ID
TTDC00127
Target Name
Growth hormone secretagogue receptor type 1
Gene Name
GHSR
Synonyms
GH-releasing peptide receptor; GHRP; GHS-R; Ghrelin receptor; Growth hormone secretagogue receptor; GHSR
Target Type
Successful
Disease Alcohol use disorders [ICD9: 303; ICD10: F10.2]
Anorexia nervosa cachexia [ICD9: 307.1, 799.4; ICD10: F50.0-F50.1]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Cachexia [ICD9: 799.4; ICD10: R64]
Carbohydrate metabolism disorder [ICD10: E73-E74]
Functional bowel disorder [ICD10: K00-K93]
Frailty [ICD10: R54]
Fibromyalgia [ICD9: 729.1; ICD10: M79.7]
Gastric motility disorder [ICD10: K22.4]
Growth hormone deficiency [ICD9: 253.0, 253.3; ICD10: E22.0, E23.0]
Ileus; Gastroparesis; Miscellaneous gastrointestinal disorders [ICD9: 530-558, 536.3, 537.2, 560.1, 560.31, 777.1, 777.4; ICD10: K20-K64, K31.5, K31.8, K56.0, K56.3, K56.7, P76.1]
Metabolic disorders [ICD9: 270-279; ICD10: E70-E89]
Obesity [ICD9: 278; ICD10: E66]
Postoperative ileus [ICD9: 537.2, 560.1, 560.31, 777.1, 777.4; ICD10: K31.5, K56.0, K56.3, K56.7, P76.1]
Type 2 diabetes [ICD9: 250; ICD10: E11]
Function
Receptor for ghrelin, coupled to G-alpha-11 proteins. Stimulates growth hormone secretion. Binds also other growth hormone releasing peptides (GHRP) (e.g. Met-enkephalin and GHRP-6) as well as non-peptide, low molecular weight secretagogues (e.g. L-692,429, MK-0677, adenosine).
BioChemical Class
GPCR rhodopsin
Target Validation
T59604
UniProt ID
Q92847
Sequence
MWNATPSEEPGFNLTLADLDWDASPGNDSLGDELLQLFPAPLLAGVTATCVALFVVGIAG
NLLTMLVVSRFRELRTTTNLYLSSMAFSDLLIFLCMPLDLVRLWQYRPWNFGDLLCKLFQ
FVSESCTYATVLTITALSVERYFAICFPLRAKVVVTKGRVKLVIFVIWAVAFCSAGPIFV
LVGVEHENGTDPWDTNECRPTEFAVRSGLLTVMVWVSSIFFFLPVFCLTVLYSLIGRKLW
RRRRGDAVVGASLRDQNHKQTVKMLAVVVFAFILCWLPFHVGRYLFSKSFEPGSLEIAQI
SQYCNLVSFVLFYLSAAINPILYNIMSKKYRVAVFRLLGFEPFSQRKLSTLKDESSRAWT
ESSINT
Drugs and Mode of Action
Drug(s) GHRP-2 Drug Info Approved Growth hormone deficiency [551871]
Ibutamoren Drug Info Approved Fibromyalgia [536647], [541176]
Anamorelin Drug Info Phase 3 Carbohydrate metabolism disorder [523546]
Macimorelin Drug Info Phase 3 Growth hormone deficiency [521987]
TZP-101 Drug Info Phase 2b Ileus; Gastroparesis; Miscellaneous gastrointestinal disorders [536527], [540467]
GTP-200 Drug Info Phase 2 Cancer [548242]
RQ-00000005 Drug Info Phase 2 Frailty [522109]
Tabimorelin Drug Info Phase 2 Growth hormone deficiency [525551]
Ipamorelin Drug Info Phase 1/2 Postoperative ileus [536527]
PF-05190457 Drug Info Phase 1 Type 2 diabetes [523786]
ST-1141 Drug Info Phase 1 Functional bowel disorder [548492]
AEZS-123 Drug Info Preclinical Alcohol use disorders [550214]
EP-01492 Drug Info Preclinical Obesity [536122]
TZP-301 Drug Info Preclinical Metabolic disorders [551744]
CYT-009-GhrQb Drug Info Discontinued in Phase 1/2 Obesity [536122]
LY-444711 Drug Info Discontinued in Phase 1 Growth hormone deficiency [547057]
SUN-11031 Drug Info Terminated Anorexia nervosa cachexia [536225]
Inhibitor 4-(3-hexylureido)-N-phenylbenzenesulfonamide Drug Info [530395]
AwFwLL-NH2 Drug Info [528740]
DprwFwLL-NH2 Drug Info [528740]
DwFwLL-NH2 Drug Info [528740]
HwFwLL-NH2 Drug Info [528740]
KwFwLL-NH2 Drug Info [528740]
QwFwLL-NH2 Drug Info [528740]
RPKPfQwFwLL-NH2 Drug Info [528740]
RwFwLL-NH2 Drug Info [528740]
WFwGG-NH2 Drug Info [528740]
WFwLL-NH2 Drug Info [528740]
Antagonist Abbott 14c Drug Info [528319]
AEZS-123 Drug Info [550214]
CYT-009-GhrQb Drug Info [536122]
EP-01492 Drug Info [536122]
EX-1311 Drug Info [543633]
GSK1614343 Drug Info [531003]
JMV3008 Drug Info [529089]
NOX-B11 Drug Info [543633]
TZP-301 Drug Info [551744]
YIL781 Drug Info [528960]
Stimulator Anamorelin Drug Info [537066]
Agonist EX-1314 Drug Info [543633]
GHRP-2 Drug Info [535349]
GSK-894281 Drug Info [543633]
GTP-200 Drug Info [544045]
LY-444711 Drug Info [527265]
Macimorelin Drug Info [550490]
RQ-00000005 Drug Info [532719]
SM-130,686 Drug Info [526224]
ST-1141 Drug Info [550985]
SUN-11031 Drug Info [536225]
TZP-101 Drug Info [537004], [537157], [537305]
[35S]ibutamoren Drug Info [534355]
Modulator Ibutamoren Drug Info [553238]
Ipamorelin Drug Info
PF-05190457 Drug Info [551215]
Tabimorelin Drug Info [525551]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway cAMP signaling pathway
Neuroactive ligand-receptor interaction
NetPath Pathway Leptin Signaling Pathway
Reactome Peptide ligand-binding receptors
G alpha (q) signalling events
WikiPathways GPCRs, Class A Rhodopsin-like
Gastrin-CREB signalling pathway via PKC and MAPK
Peptide GPCRs
GPCR ligand binding
GPCR downstream signaling
References
Ref 521987ClinicalTrials.gov (NCT00448747) Investigation of a New, Oral Growth Hormone Secretagogue, Macimorelin (AEZS-130) as a Growth Hormone Stimulation Test.. U.S. National Institutes of Health.
Ref 522109ClinicalTrials.gov (NCT00527046) Effects Of An Oral Growth Hormone Secretagogue In Older Functionally Limited Adults. U.S. National Institutes of Health.
Ref 523546ClinicalTrials.gov (NCT01395914) Anamorelin HCl in the Treatment of Non-Small Cell Lung Cancer-Cachexia (NSCLC-C): An Extension Study (ROMANA 3). U.S. National Institutes of Health.
Ref 523786ClinicalTrials.gov (NCT01522807) A Study Of Three PF-05190457 Formulations In Healthy Volunteers. U.S. National Institutes of Health.
Ref 525551Pharmacological characterisation of a new oral GH secretagogue, NN703. Eur J Endocrinol. 1999 Aug;141(2):180-9.
Ref 536122Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
Ref 536225Emerging drugs for eating disorder treatment. Expert Opin Emerg Drugs. 2006 May;11(2):315-36.
Ref 536527Emerging drugs for postoperative ileus. Expert Opin Emerg Drugs. 2007 Nov;12(4):619-26.
Ref 536647Emerging therapies for fibromyalgia. Expert Opin Emerg Drugs. 2008 Mar;13(1):53-62.
Ref 540467(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. (Ligand id: 3535).
Ref 541176(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. (Ligand id: 5867).
Ref 547057Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012573)
Ref 548242Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023682)
Ref 548492Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025998)
Ref 5502142011 Pipeline of Aeterna Zentaris.
Ref 551744Clinical pipeline report, company report or official report of Tranzyme Pharma (2011).
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 525551Pharmacological characterisation of a new oral GH secretagogue, NN703. Eur J Endocrinol. 1999 Aug;141(2):180-9.
Ref 526224Oxindole derivatives as orally active potent growth hormone secretagogues. J Med Chem. 2001 Dec 20;44(26):4641-9.
Ref 527265Synthesis and biological evaluation of an orally active ghrelin agonist that stimulates food consumption and adiposity in rats. Bioorg Med Chem Lett. 2004 Dec 6;14(23):5873-6.
Ref 528319Discovery and pharmacological evaluation of growth hormone secretagogue receptor antagonists. J Med Chem. 2006 Jul 27;49(15):4459-69.
Ref 528740J 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.
Ref 528960Small-molecule ghrelin receptor antagonists improve glucose tolerance, suppress appetite, and promote weight loss. Endocrinology. 2007 Nov;148(11):5175-85. Epub 2007 Jul 26.
Ref 529089Toward potent ghrelin receptor ligands based on trisubstituted 1,2,4-triazole structure. 2. Synthesis and pharmacological in vitro and in vivo evaluations. J Med Chem. 2007 Nov 15;50(23):5790-806. Epub 2007 Oct 10.
Ref 530395Bioorg 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.
Ref 531003Discovery process and characterization of novel carbohydrazide derivatives as potent and selective GHSR1a antagonists. ChemMedChem. 2010 Sep 3;5(9):1450-5.
Ref 532719Hypotensive effects of ghrelin receptor agonists mediated through a novel receptor. Br J Pharmacol. 2014 Mar;171(5):1275-86.
Ref 534355Molecular analysis of rat pituitary and hypothalamic growth hormone secretagogue receptors. Mol Endocrinol. 1997 Apr;11(4):415-23.
Ref 535349GH-releasing peptide-2 increases fat mass in mice lacking NPY: indication for a crucial mediating role of hypothalamic agouti-related protein. Endocrinology. 2002 Feb;143(2):558-68.
Ref 536122Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
Ref 536225Emerging drugs for eating disorder treatment. Expert Opin Emerg Drugs. 2006 May;11(2):315-36.
Ref 537004Effect of the ghrelin receptor agonist TZP-101 on colonic transit in a rat model of postoperative ileus. Eur J Pharmacol. 2009 Feb 14;604(1-3):132-7. Epub 2008 Dec 14.
Ref 537066Pharmacodynamic hormonal effects of anamorelin, a novel oral ghrelin mimetic and growth hormone secretagogue in healthy volunteers. Growth Horm IGF Res. 2009 Jun;19(3):267-73. Epub 2009 Feb 3.
Ref 537157Ghrelin receptor agonist (TZP-101) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis. Aliment Pharmacol Ther. 2009 Jun 1;29(11):1179-87. Epub 2009 Feb 27.
Ref 537305Contribution of protein binding to the pharmacokinetics of the ghrelin receptor agonist TZP-101 in healthy volunteers and adults with symptomatic gastroparesis: two randomized, double-blind studies and a binding profile study. Clin Drug Investig. 2009;29(6):409-18. doi: 10.2165/00044011-200929060-00004.
Ref 543633(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: 246).
Ref 544045Orphan GPCR research. Br J Pharmacol. 2008 March; 153(Suppl 1): S339-S346.
Ref 5502142011 Pipeline of Aeterna Zentaris.
Ref 550490National Cancer Institute Drug Dictionary (drug id 735530).
Ref 550985The Prokinetic Face of Ghrelin. International Journal of Peptides Volume 2010 (2010), Article ID 493614, Page(11).
Ref 551215A gift for research. SciBX 7(6); doi:10.1038/scibx.2014.160. Feb. 13 2014
Ref 551744Clinical pipeline report, company report or official report of Tranzyme Pharma (2011).
Ref 553238Identification of a new G-protein-linked receptor for growth hormone secretagogues. Mol Endocrinol. 1996 Jan;10(1):57-61.

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