Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT94U6MO)

DOT Name Somatoliberin (GHRH)
Synonyms Growth hormone-releasing factor; GRF; Growth hormone-releasing hormone; GHRH; Somatocrinin; Somatorelin; Sermorelin
Gene Name GHRH
Related Disease
Adenoma ( )
Acute myelogenous leukaemia ( )
Adult glioblastoma ( )
Benign prostatic hyperplasia ( )
Brachydactyly ( )
Breast carcinoma ( )
Carcinoma ( )
Endometrial carcinoma ( )
Endometriosis ( )
Epithelial ovarian cancer ( )
Gastric cancer ( )
Glioblastoma multiforme ( )
High blood pressure ( )
Hypogonadotropic hypogonadism ( )
Hypogonadotropic hypogonadism 23 with or without anosmia ( )
Hypopituitarism ( )
Isolated growth hormone deficiency type IA ( )
Isolated growth hormone deficiency, type 5 ( )
Kallmann syndrome ( )
Lung cancer ( )
Lung carcinoma ( )
Multiple endocrine neoplasia type 1 ( )
Non-small-cell lung cancer ( )
Obesity ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Pancreatic tumour ( )
Panhypopituitarism ( )
Prader-Willi syndrome ( )
Prostate cancer ( )
Prostate carcinoma ( )
Prostatitis ( )
Pseudohypoparathyroidism ( )
Pulmonary edema ( )
Type-1/2 diabetes ( )
Melanoma ( )
Neuroblastoma ( )
Pituitary dwarfism ( )
Small-cell lung cancer ( )
Acromegaly ( )
Breast neoplasm ( )
Diabetic retinopathy ( )
Endometrial cancer ( )
Myocardial infarction ( )
Pituitary gland disorder ( )
Prostate neoplasm ( )
Pseudohypoparathyroidism type 1A ( )
Triple negative breast cancer ( )
UniProt ID
SLIB_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
5BQM; 7CZ5; 7V9M
Pfam ID
PF00123
Sequence
MPLWVFFFVILTLSNSSHCSPPPPLTLRMRRYADAIFTNSYRKVLGQLSARKLLQDIMSR
QQGESNQERGARARLGRQVDSMWAEQKQMELESILVALLQKHSRNSQG
Function GRF is released by the hypothalamus and acts on the adenohypophyse to stimulate the secretion of growth hormone.
KEGG Pathway
Neuroactive ligand-receptor interaction (hsa04080 )
Growth hormone synthesis, secretion and action (hsa04935 )
Reactome Pathway
Glucagon-type ligand receptors (R-HSA-420092 )
G alpha (s) signalling events (R-HSA-418555 )

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adenoma DIS78ZEV Definitive Biomarker [1]
Acute myelogenous leukaemia DISCSPTN Strong Biomarker [2]
Adult glioblastoma DISVP4LU Strong Altered Expression [3]
Benign prostatic hyperplasia DISI3CW2 Strong Biomarker [4]
Brachydactyly DIS2533F Strong Biomarker [5]
Breast carcinoma DIS2UE88 Strong Biomarker [6]
Carcinoma DISH9F1N Strong Biomarker [6]
Endometrial carcinoma DISXR5CY Strong Biomarker [7]
Endometriosis DISX1AG8 Strong Altered Expression [8]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [9]
Gastric cancer DISXGOUK Strong Biomarker [10]
Glioblastoma multiforme DISK8246 Strong Biomarker [11]
High blood pressure DISY2OHH Strong Genetic Variation [12]
Hypogonadotropic hypogonadism DIS8JSKR Strong Biomarker [13]
Hypogonadotropic hypogonadism 23 with or without anosmia DISYNM6Y Strong Biomarker [13]
Hypopituitarism DIS1QT3G Strong Biomarker [13]
Isolated growth hormone deficiency type IA DISLPIAM Strong Biomarker [13]
Isolated growth hormone deficiency, type 5 DISVY7CR Strong Biomarker [13]
Kallmann syndrome DISO3HDG Strong Biomarker [13]
Lung cancer DISCM4YA Strong Genetic Variation [14]
Lung carcinoma DISTR26C Strong Genetic Variation [14]
Multiple endocrine neoplasia type 1 DIS0RJRK Strong Biomarker [15]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [16]
Obesity DIS47Y1K Strong Altered Expression [17]
Ovarian cancer DISZJHAP Strong Biomarker [9]
Ovarian neoplasm DISEAFTY Strong Biomarker [9]
Pancreatic tumour DIS3U0LK Strong Biomarker [18]
Panhypopituitarism DISAKJ4T Strong Biomarker [19]
Prader-Willi syndrome DISYWMLU Strong Genetic Variation [20]
Prostate cancer DISF190Y Strong Biomarker [21]
Prostate carcinoma DISMJPLE Strong Biomarker [21]
Prostatitis DISL8OGN Strong Biomarker [22]
Pseudohypoparathyroidism DIS183OJ Strong Biomarker [23]
Pulmonary edema DISNPHO6 Strong Therapeutic [24]
Type-1/2 diabetes DISIUHAP Strong Biomarker [25]
Melanoma DIS1RRCY moderate Biomarker [26]
Neuroblastoma DISVZBI4 moderate Altered Expression [27]
Pituitary dwarfism DISI019B moderate Genetic Variation [28]
Small-cell lung cancer DISK3LZD moderate Biomarker [29]
Acromegaly DISCC73U Limited Biomarker [30]
Breast neoplasm DISNGJLM Limited Biomarker [31]
Diabetic retinopathy DISHGUJM Limited Biomarker [25]
Endometrial cancer DISW0LMR Limited Biomarker [7]
Myocardial infarction DIS655KI Limited Therapeutic [32]
Pituitary gland disorder DIS7XB48 Limited Biomarker [33]
Prostate neoplasm DISHDKGQ Limited Genetic Variation [34]
Pseudohypoparathyroidism type 1A DISSOR3M Limited Biomarker [5]
Triple negative breast cancer DISAMG6N Limited Biomarker [35]
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⏷ Show the Full List of 48 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Somatoliberin (GHRH). [36]
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2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Somatoliberin (GHRH). [37]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Somatoliberin (GHRH). [38]
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References

1 Use of the metallothionein promoter-human growth hormone-releasing hormone (GHRH) mouse to identify regulatory pathways that suppress pituitary somatotrope hyperplasia and adenoma formation due to GHRH-receptor hyperactivation.Endocrinology. 2009 Jul;150(7):3177-85. doi: 10.1210/en.2008-1482. Epub 2009 Apr 2.
2 A new approach to the treatment of acute myeloid leukaemia targeting the receptor for growth hormone-releasing hormone.Br J Haematol. 2018 May;181(4):476-485. doi: 10.1111/bjh.15207. Epub 2018 Apr 16.
3 Prognosis in human glioblastoma based on expression of ligand growth hormone-releasing hormone, pituitary-type growth hormone-releasing hormone receptor, its splicing variant receptors, EGF receptor and PTEN genes.J Cancer Res Clin Oncol. 2014 Oct;140(10):1641-9. doi: 10.1007/s00432-014-1716-1. Epub 2014 Jun 1.
4 P53, GHRH, inflammation and cancer.EBioMedicine. 2018 Nov;37:557-562. doi: 10.1016/j.ebiom.2018.10.034. Epub 2018 Oct 19.
5 Novel Opportunities for Improving the Quality of Preanalytical Phase. A Glimpse to the Future?.J Med Biochem. 2017 Oct 28;36(4):293-300. doi: 10.1515/jomb-2017-0029. eCollection 2017 Oct.
6 The expression of GHRH and its receptors in breast carcinomas with apocrine differentiation-further evidence of the presence of a GHRH pathway in these tumors.Hum Pathol. 2017 Jun;64:164-170. doi: 10.1016/j.humpath.2017.03.026. Epub 2017 Apr 21.
7 Growth hormone-releasing hormone antagonist inhibits the invasiveness of human endometrial cancer cells by down-regulating twist and N-cadherin expression.Oncotarget. 2017 Jan 17;8(3):4410-4421. doi: 10.18632/oncotarget.13877.
8 Effects of an Antagonistic Analog of Growth Hormone-Releasing Hormone on Endometriosis in a Mouse Model and In Vitro.Reprod Sci. 2017 Nov;24(11):1503-1511. doi: 10.1177/1933719117691140. Epub 2017 Feb 16.
9 Growth hormone-releasing hormone antagonists inhibit growth of human ovarian cancer.Horm Metab Res. 2011 Oct;43(11):816-20. doi: 10.1055/s-0031-1287766. Epub 2011 Oct 18.
10 The expression of growth hormone-releasing hormone (GHRH) and splice variants of its receptor in human gastroenteropancreatic carcinomas.Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11866-71. doi: 10.1073/pnas.182433099. Epub 2002 Aug 19.
11 Magnetoelectric nanoparticles for delivery of antitumor peptides into glioblastoma cells by magnetic fields.Nanomedicine (Lond). 2018 Feb;13(4):423-438. doi: 10.2217/nnm-2017-0300. Epub 2018 Jan 18.
12 Common variants at somatostatin are significantly associated with hypertension incidence in smoking and drinking populations.J Am Soc Hypertens. 2018 Mar;12(3):230-237.e12. doi: 10.1016/j.jash.2017.12.009. Epub 2017 Dec 28.
13 GH, but not GHRH, plays a role in the development of experimental autoimmune encephalomyelitis.Endocrinology. 2011 Oct;152(10):3803-10. doi: 10.1210/en.2011-1317. Epub 2011 Aug 16.
14 Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of human malignant pleural mesothelioma.Proc Natl Acad Sci U S A. 2019 Feb 5;116(6):2226-2231. doi: 10.1073/pnas.1818865116. Epub 2019 Jan 18.
15 Growth hormone-releasing hormone-producing pancreatic neuroendocrine tumor in a multiple endocrine neoplasia type 1 family with an uncommon phenotype.Eur J Gastroenterol Hepatol. 2013 Jul;25(7):858-62. doi: 10.1097/MEG.0b013e32835f433f.
16 GHRH antagonist inhibits focal adhesion kinase (FAK) and decreases expression of vascular endothelial growth factor (VEGF) in human lung cancer cells in vitro.Peptides. 2012 Sep;37(1):63-8. doi: 10.1016/j.peptides.2012.07.010. Epub 2012 Jul 20.
17 Cold exposure promotes obesity and impairs glucose homeostasis in mice subjected to a highfat diet.Mol Med Rep. 2018 Oct;18(4):3923-3931. doi: 10.3892/mmr.2018.9382. Epub 2018 Aug 10.
18 Pituitary tumors and hyperplasia in multiple endocrine neoplasia type 1 syndrome (MEN1): a case-control study in a series of 77 patients versus 2509 non-MEN1 patients.Am J Surg Pathol. 2008 Apr;32(4):534-43. doi: 10.1097/PAS.0b013e31815ade45.
19 Molecular screening of a large cohort of Moroccan patients with congenital hypopituitarism.Clin Endocrinol (Oxf). 2015 Jun;82(6):876-84. doi: 10.1111/cen.12706. Epub 2015 Feb 6.
20 Deconvolution-based assessment of pituitary GH secretion stimulated with GHRH+arginine in Prader-Willi adults and obese controls.Clin Endocrinol (Oxf). 2013 Aug;79(2):224-31. doi: 10.1111/cen.12142. Epub 2013 Apr 5.
21 Stimulation of neuroendocrine differentiation in prostate cancer cells by GHRH and its blockade by GHRH antagonists.Invest New Drugs. 2020 Jun;38(3):746-754. doi: 10.1007/s10637-019-00831-2. Epub 2019 Jul 17.
22 Growth hormone-releasing hormone antagonists reduce prostatic enlargement and inflammation in carrageenan-induced chronic prostatitis.Prostate. 2018 Sep;78(13):970-980. doi: 10.1002/pros.23655. Epub 2018 May 21.
23 A sporadic case of pseudohypoparathyroidism type 1 and idiopathic primary adrenal insufficiency associated with a novel mutation in the GNAS1 gene.Endocr Pract. 2014 Oct;20(10):e202-6. doi: 10.4158/EP14020.CR.
24 Agonist of growth hormone-releasing hormone reduces pneumolysin-induced pulmonary permeability edema.Proc Natl Acad Sci U S A. 2012 Feb 7;109(6):2084-9. doi: 10.1073/pnas.1121075109. Epub 2012 Jan 23.
25 Actions and Potential Therapeutic Applications of Growth Hormone-Releasing Hormone Agonists.Endocrinology. 2019 Jul 1;160(7):1600-1612. doi: 10.1210/en.2019-00111.
26 Novel GHRH antagonists suppress the growth of human malignant melanoma by restoring nuclear p27 function.Cell Cycle. 2014;13(17):2790-7. doi: 10.4161/15384101.2015.945879.
27 Expression of Ras-GRF in the SK-N-BE neuroblastoma accelerates retinoic-acid-induced neuronal differentiation and increases the functional expression of the IRK1 potassium channel.Eur J Neurosci. 1999 Mar;11(3):959-66. doi: 10.1046/j.1460-9568.1999.00504.x.
28 Behavioural phenotyping, learning and memory in young and aged growth hormone-releasing hormone-knockout mice.Endocr Connect. 2018 Aug 1;7(8):924-931. doi: 10.1530/EC-18-0165.
29 Inhibition of experimental small-cell and non-small-cell lung cancers by novel antagonists of growth hormone-releasing hormone.Int J Cancer. 2018 Jun 1;142(11):2394-2404. doi: 10.1002/ijc.31308. Epub 2018 Mar 1.
30 Primary pituitary diffuse large B-cell lymphoma with somatotroph hyperplasia and acromegaly: case report.J Neurosurg. 2017 May;126(5):1725-1730. doi: 10.3171/2016.5.JNS16828. Epub 2016 Aug 12.
31 Stimulation of proliferation of MCF-7 breast cancer cells by a transfected splice variant of growth hormone-releasing hormone receptor.Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5575-9. doi: 10.1073/pnas.0700407104. Epub 2007 Mar 19.
32 Synthesis of new potent agonistic analogs of growth hormone-releasing hormone (GHRH) and evaluation of their endocrine and cardiac activities.Peptides. 2014 Feb;52:104-12. doi: 10.1016/j.peptides.2013.12.010. Epub 2013 Dec 25.
33 Ghrelin stimulates growth hormone release from the pituitary via hypothalamic growth hormone-releasing hormone neurons in the cichlid, Oreochromis niloticus.Cell Tissue Res. 2018 Nov;374(2):349-365. doi: 10.1007/s00441-018-2870-6. Epub 2018 Jun 23.
34 Expression of growth hormone-releasing hormone and its receptor splice variants in human prostate cancer.J Clin Endocrinol Metab. 2002 Oct;87(10):4707-14. doi: 10.1210/jc.2002-020347.
35 Expression of GHRH-R, a Potentially Targetable Biomarker, in Triple-negative Breast Cancer.Appl Immunohistochem Mol Morphol. 2018 Jan;26(1):1-5. doi: 10.1097/PAI.0000000000000622.
36 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.
37 Involvement of the Endocrine-Disrupting Chemical Bisphenol A (BPA) in Human Placentation. J Clin Med. 2020 Feb 3;9(2):405. doi: 10.3390/jcm9020405.
38 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.