Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTKMAZ6)

• DTT Name: Growth hormone receptor (GHR)
• Synonyms: Somatotropin receptor; Serum bindingprotein; GH receptor
• Gene Name: GHR
• DTT Type: Successful target; [1]
• BioChemical Class: Cytokine receptor
• UniProt ID: GHR_HUMAN
• TTD ID: T02333
• Sequence:
  MDLWQLLLTLALAGSSDAFSGSEATAAILSRAPWSLQSVNPGLKTNSSKEPKFTKCRSPE
  RETFSCHWTDEVHHGTKNLGPIQLFYTRRNTQEWTQEWKECPDYVSAGENSCYFNSSFTS
  IWIPYCIKLTSNGGTVDEKCFSVDEIVQPDPPIALNWTLLNVSLTGIHADIQVRWEAPRN
  ADIQKGWMVLEYELQYKEVNETKWKMMDPILTTSVPVYSLKVDKEYEVRVRSKQRNSGNY
  GEFSEVLYVTLPQMSQFTCEEDFYFPWLLIIIFGIFGLTVMLFVFLFSKQQRIKMLILPP
  VPVPKIKGIDPDLLKEGKLEEVNTILAIHDSYKPEFHSDDSWVEFIELDIDEPDEKTEES
  DTDRLLSSDHEKSHSNLGVKDGDSGRTSCCEPDILETDFNANDIHEGTSEVAQPQRLKGE
  ADLLCLDQKNQNNSPYHDACPATQQPSVIQAEKNKPQPLPTEGAESTHQAAHIQLSNPSS
  LSNIDFYAQVSDITPAGSVVLSPGQKNKAGMSQCDMHPEMVSLCQENFLMDNAYFCEADA
  KKCIPVAPHIKVESHIQPSLNQEDIYITTESLTTAAGRPGTGEHVPGSEMPVPDYTSIHI
  VQSPQGLILNATALPLPDKEFLSSCGYVSTDQLNKIMP
• Function: On ligand binding, couples to the JAK2/STAT5 pathway. Receptor for pituitary gland growth hormone involved in regulating postnatal body growth.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Neuroactive ligand-receptor interaction (hsa04080)
  PI3K-Akt signaling pathway (hsa04151)
  Jak-STAT signaling pathway (hsa04630)
• Reactome Pathway:
  Growth hormone receptor signaling (R-HSA-982772)
  Prolactin receptor signaling (R-HSA-1170546)

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pegvisomant	DMDEZI3	Acromegaly	5A60.0	Approved	[1]
Somatropin recombinant	DMF3GM2	Fetal growth restriction	KA20.1Z	Approved	[2]

6 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
IONIS-GHR-LRx	DMQ9711	Acromegaly	5A60.0	Phase 2	[3]
PH-794428	DM71HVW	Growth hormone deficiency	5A61.3	Phase 2	[4]
SKF-110679	DMNRHMX	Growth hormone deficiency	5A61.3	Phase 2	[5]
EP-51216	DM49RI7	Eating disorder	6B82	Phase 1	[6]
EP-51389	DMW739O	Eating disorder	6B82	Phase 1	[6]
Syntropin	DMH76KD	Dwarfism	5B11	Phase 1	[7]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AOD-9604	DMGDPSI	Obesity	5B81	Discontinued in Phase 2	[8]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BVT-A	DMDSX58	Acromegaly	5A60.0	Preclinical	[9]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NNC-26-0194	DMDCPFJ	Discovery agent	N.A.	Investigative	[10]

References

• [1] Growth hormone receptor antagonist treatment reduces exercise performance in young males. J Clin Endocrinol Metab. 2009 Sep;94(9):3265-72.
• [2] Cost-utility of somatropin (rDNA origin) in the treatment of growth hormone deficiency in children. Curr Med Res Opin. 2006 Feb;22(2):351-7.
• [3] ClinicalTrials.gov (NCT04522180) An Open Label, Randomized, Phase 2 Study to Assess the Safety, Tolerability, and Efficacy of IONIS-GHR-LRx, an Antisense Inhibitor of the Growth Hormone Receptor, Administered Monthly as Monotherapy in Patients With Acromegaly. U.S.National Institutes of Health.
• [4] PEGylation of somatropin (recombinant human growth hormone): impact on its clearance in humans.Xenobiotica.2008 Oct;38(10):1340-51.
• [5] 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. (Ligand id: 1093).
• [6] Emerging drugs for eating disorder treatment. Expert Opin Emerg Drugs. 2006 May;11(2):315-36.
• [7] Late feedback effects of hypothalamic-pituitary-adrenal axis hormones in healthy subjects. Psychoneuroendocrinology. 1998 May;23(4):371-83.
• [8] Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
• [9] Emerging drugs for acromegaly. Expert Opin Emerg Drugs. 2008 Jun;13(2):273-93.
• [10] Pharmacokinetic evaluation of ipamorelin and other peptidyl growth hormone secretagogues with emphasis on nasal absorption. Xenobiotica. 1998 Nov;28(11):1083-92.