Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT92RTRD)

• DOT Name: Somatotropin (GH1)
• Synonyms: Growth hormone; GH; GH-N; Growth hormone 1; Pituitary growth hormone
• Gene Name: GH1
• Related Disease:
  Isolated growth hormone deficiency type IA
  Isolated growth hormone deficiency type II
  Isolated growth hormone deficiency type IB
  Short stature due to growth hormone qualitative anomaly
• UniProt ID: SOMA_HUMAN
• PDB ID: 1A22; 1AXI; 1BP3; 1HGU; 1HUW; 1HWG; 1HWH; 1KF9; 3HHR; 6QIO
• Pfam ID: PF00103
• Sequence:
  MATGSRTSLLLAFGLLCLPWLQEGSAFPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEA
  YIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLR
  SVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDD
  ALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF
• Function: Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF-1. It stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Neuroactive ligand-receptor interaction (hsa04080)
  PI3K-Akt sig.ling pathway (hsa04151)
  JAK-STAT sig.ling pathway (hsa04630)
  Growth hormone synthesis, secretion and action (hsa04935)
• Reactome Pathway:
  Synthesis, secretion, and deacylation of Ghrelin (R-HSA-422085)
  Growth hormone receptor signaling (R-HSA-982772)
  Prolactin receptor signaling (R-HSA-1170546)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Isolated growth hormone deficiency type IA	DISLPIAM	Definitive	Autosomal recessive	[1]
Isolated growth hormone deficiency type II	DISH3EO5	Strong	Autosomal dominant	[1]
Isolated growth hormone deficiency type IB	DISU7Q3J	Supportive	Autosomal recessive	[2]
Short stature due to growth hormone qualitative anomaly	DIS21OA7	Supportive	Autosomal recessive	[3]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Somatotropin (GH1) increases the response to substance of Arsenic trioxide.	[24]
Enalapril	DMNFUZR	Approved	Somatotropin (GH1) increases the response to substance of Enalapril.	[25]

This DOT Affected the Regulation of Drug Effects of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
AMG 386	DMQJXL4	Phase 3	Somatotropin (GH1) increases the abundance of AMG 386.	[26]
L-thyroxine	DM83HWL	Investigative	Somatotropin (GH1) decreases the abundance of L-thyroxine.	[26]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Somatotropin (GH1).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Somatotropin (GH1).	[19]

13 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Somatotropin (GH1).	[5]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Somatotropin (GH1).	[5]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Somatotropin (GH1).	[8]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone increases the expression of Somatotropin (GH1).	[9]
Clonidine	DM6RZ9Q	Approved	Clonidine increases the expression of Somatotropin (GH1).	[11]
Levodopa	DMN3E57	Approved	Levodopa increases the expression of Somatotropin (GH1).	[12]
Octreotide	DMHIDCJ	Approved	Octreotide decreases the expression of Somatotropin (GH1).	[13]
Bromocriptine	DMVE3TK	Approved	Bromocriptine decreases the expression of Somatotropin (GH1).	[14]
Cenestin	DMXQS7K	Approved	Cenestin increases the expression of Somatotropin (GH1).	[5]
Cyproheptadine	DM92AH3	Approved	Cyproheptadine increases the expression of Somatotropin (GH1).	[15]
Connexyn	DMF29Q5	Approved	Connexyn increases the expression of Somatotropin (GH1).	[16]
Sodium oxybate	DMBOV5P	Approved	Sodium oxybate increases the expression of Somatotropin (GH1).	[18]
Apomorphine SL	DMPH7EO	Investigative	Apomorphine SL increases the expression of Somatotropin (GH1).	[22]

12 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Progesterone	DMUY35B	Approved	Progesterone increases the secretion of Somatotropin (GH1).	[6]
Ethanol	DMDRQZU	Approved	Ethanol affects the folding of Somatotropin (GH1).	[7]
Adenosine triphosphate	DM79F6G	Approved	Adenosine triphosphate increases the secretion of Somatotropin (GH1).	[10]
Polyethylene glycol	DM4I1JP	Approved	Polyethylene glycol affects the folding of Somatotropin (GH1).	[7]
Gamma hydroxybutyric acid	DMGBKVD	Approved	Gamma hydroxybutyric acid increases the secretion of Somatotropin (GH1).	[17]
HSDB-674	DMJG4WR	Phase 1	HSDB-674 affects the folding of Somatotropin (GH1).	[7]
Examorelin	DMGJMQH	Discontinued in Phase 2	Examorelin increases the secretion of Somatotropin (GH1).	[20]
Forskolin	DM6ITNG	Investigative	Forskolin increases the secretion of Somatotropin (GH1).	[21]
2-Propanol, Isopropanol	DML5O0H	Investigative	2-Propanol, Isopropanol affects the folding of Somatotropin (GH1).	[7]
Trifluoroethanol	DMAWTUL	Investigative	Trifluoroethanol affects the folding of Somatotropin (GH1).	[7]
2-Methyl-2-Propanol	DMHM5GJ	Investigative	2-Methyl-2-Propanol affects the folding of Somatotropin (GH1).	[7]
N-propylnorapomorphine	DMO7MTX	Investigative	N-propylnorapomorphine affects the secretion of Somatotropin (GH1).	[23]

References

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• [11] Assessment of MK-912, an alpha 2-adrenoceptor antagonist, with use of intravenous clonidine. Clin Pharmacol Ther. 1989 Jul;46(1):103-9. doi: 10.1038/clpt.1989.113.
• [12] Effects of terguride on anterior pituitary function in parkinsonian patients treated with L-dopa: a double-blind study versus placebo. Clin Neuropharmacol. 1996 Feb;19(1):72-80. doi: 10.1097/00002826-199619010-00006.
• [13] Effect of a somatostatin analogue, octreotide, on renal haemodynamics and albuminuria in acromegalic patients. Eur J Clin Invest. 1992 Jul;22(7):494-502. doi: 10.1111/j.1365-2362.1992.tb01496.x.
• [14] Improvement of congestive heart failure after octreotide and transsphenoidal surgery in a patient with acromegaly. Intern Med. 2009;48(9):697-700. doi: 10.2169/internalmedicine.48.1537. Epub 2009 May 1.
• [15] [Toxicity of cyproheptadine. Side effects and accidental overdosage (author's transl)]. Monatsschr Kinderheilkd (1902). 1978 Mar;126(3):123-6.
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• [17] Thyrotropin-releasing hormone-induced GH release after cocaine withdrawal in cocaine addicts. Neuropeptides. 1999 Dec;33(6):522-5. doi: 10.1054/npep.1999.0773.
• [18] Failure of gammahydroxy butyric acid to stimulate growth hormone secretion in cocaine addicts. Neuropeptides. 1997 Oct;31(5):459-62. doi: 10.1016/s0143-4179(97)90040-8.
• [19] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [20] The effect of hexarelin on growth hormone (GH) secretion in patients with GH deficiency. J Clin Endocrinol Metab. 1995 Sep;80(9):2692-6. doi: 10.1210/jcem.80.9.7673411.
• [21] Growth hormone (GH) deficiency type II: a novel GH-1 gene mutation (GH-R178H) affecting secretion and action. J Clin Endocrinol Metab. 2010 Feb;95(2):731-9. doi: 10.1210/jc.2009-1247. Epub 2009 Dec 1.
• [22] A study of dopaminergic sensitivity in Parkinson's disease: comparison in "de novo" and levodopa-treated patients. Clin Neuropharmacol. 1996 Oct;19(5):420-7. doi: 10.1097/00002826-199619050-00005.
• [23] Treatment of Parkinson's disease with aporphines. Possible role of growth hormone. N Engl J Med. 1976 Mar 11;294(11):567-72. doi: 10.1056/NEJM197603112941101.
• [24] Autocrine human growth hormone increases sensitivity of mammary carcinoma cell to arsenic trioxide-induced apoptosis. Mol Cell Endocrinol. 2013 Sep 5;377(1-2):84-92. doi: 10.1016/j.mce.2013.07.002. Epub 2013 Jul 10.
• [25] Growth hormone aggravates renal abnormalities induced by neonatal enalapril treatment. Pediatr Nephrol. 2003 Sep;18(9):878-86. doi: 10.1007/s00467-003-1197-y. Epub 2003 Jul 23.
• [26] Recombinant human growth hormone in abstinent androgenic-anabolic steroid use: psychological, endocrine and trophic factor effects. Curr Neurovasc Res. 2007 Feb;4(1):9-18. doi: 10.2174/156720207779940699.