Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8JDFNI)

DOT Name Gastrin-releasing peptide (GRP)
Synonyms GRP
Gene Name GRP
Related Disease
Adenocarcinoma ( )
Epithelial ovarian cancer ( )
Ovarian neoplasm ( )
Advanced cancer ( )
Benign prostatic hyperplasia ( )
Breast carcinoma ( )
Breast neoplasm ( )
Carcinoma ( )
Clear cell renal carcinoma ( )
Colorectal carcinoma ( )
Esophageal squamous cell carcinoma ( )
Gastric cancer ( )
Gastrin-producing neuroendocrine tumor ( )
Hepatocellular carcinoma ( )
Metastatic malignant neoplasm ( )
Neuroendocrine neoplasm ( )
Non-small-cell lung cancer ( )
Obesity ( )
Osteoarthritis ( )
Ovarian cancer ( )
Pachyonychia congenita 3 ( )
Parkinson disease ( )
Prostate cancer ( )
Prostate carcinoma ( )
Prostate neoplasm ( )
Renal cell carcinoma ( )
Small-cell lung cancer ( )
Squamous cell carcinoma ( )
Stomach cancer ( )
Carcinoid tumor ( )
Colon cancer ( )
Colon carcinoma ( )
Head and neck cancer ( )
Head and neck neoplasm ( )
Head-neck squamous cell carcinoma ( )
Lung adenocarcinoma ( )
Lung neoplasm ( )
Adult glioblastoma ( )
Asthma ( )
Autism spectrum disorder ( )
Chronic kidney disease ( )
Glioblastoma multiforme ( )
Neuroblastoma ( )
Rheumatoid arthritis ( )
Schizophrenia ( )
UniProt ID
GRP_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2N0B; 2N0C; 2N0D; 2N0E; 2N0F; 2N0G; 2N0H; 7W3Z
Pfam ID
PF02044
Sequence
MRGRELPLVLLALVLCLAPRGRAVPLPAGGGTVLTKMYPRGNHWAVGHLMGKKSTGESSS
VSERGSLKQQLREYIRWEEAARNLLGLIEAKENRNHQPPQPKALGNQQPSWDSEDSSNFK
DVGSKGKVGRLSAPGSQREGRNPQLNQQ
Function
Stimulates the release of gastrin and other gastrointestinal hormones. Contributes to the perception of prurient stimuli and to the transmission of itch signals in the spinal cord that promote scratching behavior. Contributes primarily to nonhistaminergic itch sensation. In one study, shown to act in the amygdala as part of an inhibitory network which inhibits memory specifically related to learned fear. In another study, shown to act on vasoactive intestinal peptide (VIP)-expressing cells in the auditory cortex, most likely via extrasynaptic diffusion from local and long-range sources, to mediate disinhibition of glutamatergic cells via VIP cell-specific GRPR signaling which leads to enhanced auditory fear memories. Contributes to the regulation of food intake. Inhibits voltage-gated sodium channels but enhances voltage-gated potassium channels in hippocampal neurons. Induces sighing by acting directly on the pre-Botzinger complex, a cluster of several thousand neurons in the ventrolateral medulla responsible for inspiration during respiratory activity; [Neuromedin-C]: Induces an itch response through activation of receptors present on mast cells, triggering mast cell degranulation.
KEGG Pathway
Neuroactive ligand-receptor interaction (hsa04080 )
Reactome Pathway
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) (R-HSA-381771 )
G alpha (q) signalling events (R-HSA-416476 )
Peptide ligand-binding receptors (R-HSA-375276 )

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adenocarcinoma DIS3IHTY Definitive Altered Expression [1]
Epithelial ovarian cancer DIS56MH2 Definitive Biomarker [2]
Ovarian neoplasm DISEAFTY Definitive Biomarker [3]
Advanced cancer DISAT1Z9 Strong Biomarker [4]
Benign prostatic hyperplasia DISI3CW2 Strong Biomarker [5]
Breast carcinoma DIS2UE88 Strong Altered Expression [6]
Breast neoplasm DISNGJLM Strong Biomarker [7]
Carcinoma DISH9F1N Strong Biomarker [8]
Clear cell renal carcinoma DISBXRFJ Strong Altered Expression [9]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [10]
Esophageal squamous cell carcinoma DIS5N2GV Strong Biomarker [11]
Gastric cancer DISXGOUK Strong Altered Expression [12]
Gastrin-producing neuroendocrine tumor DIS8TYKO Strong Biomarker [13]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [14]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [15]
Neuroendocrine neoplasm DISNPLOO Strong Biomarker [4]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [16]
Obesity DIS47Y1K Strong Biomarker [17]
Osteoarthritis DIS05URM Strong Altered Expression [18]
Ovarian cancer DISZJHAP Strong Biomarker [19]
Pachyonychia congenita 3 DISZLC6C Strong Biomarker [20]
Parkinson disease DISQVHKL Strong Biomarker [21]
Prostate cancer DISF190Y Strong Biomarker [22]
Prostate carcinoma DISMJPLE Strong Biomarker [22]
Prostate neoplasm DISHDKGQ Strong Biomarker [23]
Renal cell carcinoma DISQZ2X8 Strong Altered Expression [9]
Small-cell lung cancer DISK3LZD Strong Biomarker [24]
Squamous cell carcinoma DISQVIFL Strong Altered Expression [25]
Stomach cancer DISKIJSX Strong Altered Expression [12]
Carcinoid tumor DISMNRDC moderate Biomarker [26]
Colon cancer DISVC52G moderate Biomarker [27]
Colon carcinoma DISJYKUO moderate Biomarker [27]
Head and neck cancer DISBPSQZ moderate Biomarker [28]
Head and neck neoplasm DIS1OB2G moderate Biomarker [28]
Head-neck squamous cell carcinoma DISF7P24 moderate Biomarker [29]
Lung adenocarcinoma DISD51WR moderate Biomarker [30]
Lung neoplasm DISVARNB Disputed Altered Expression [31]
Adult glioblastoma DISVP4LU Limited Biomarker [32]
Asthma DISW9QNS Limited Biomarker [33]
Autism spectrum disorder DISXK8NV Limited Biomarker [34]
Chronic kidney disease DISW82R7 Limited Biomarker [35]
Glioblastoma multiforme DISK8246 Limited Biomarker [32]
Neuroblastoma DISVZBI4 Limited Biomarker [36]
Rheumatoid arthritis DISTSB4J Limited Biomarker [37]
Schizophrenia DISSRV2N Limited Altered Expression [38]
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⏷ Show the Full List of 45 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
7 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Gastrin-releasing peptide (GRP). [39]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Gastrin-releasing peptide (GRP). [40]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Gastrin-releasing peptide (GRP). [41]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Gastrin-releasing peptide (GRP). [42]
Triclosan DMZUR4N Approved Triclosan increases the expression of Gastrin-releasing peptide (GRP). [43]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Gastrin-releasing peptide (GRP). [42]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Gastrin-releasing peptide (GRP). [42]
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⏷ Show the Full List of 7 Drug(s)
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 increases the methylation of Gastrin-releasing peptide (GRP). [44]
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References

1 Evidence of prognostic relevant expression profiles of heat-shock proteins and glucose-regulated proteins in oesophageal adenocarcinomas.PLoS One. 2012;7(7):e41420. doi: 10.1371/journal.pone.0041420. Epub 2012 Jul 24.
2 Inhibition of growth of ES-2 human ovarian cancers by bombesin antagonist RC-3095, and luteinizing hormone-releasing hormone antagonist Cetrorelix.Cancer Lett. 2001 Sep 28;171(1):37-45. doi: 10.1016/s0304-3835(01)00543-2.
3 The presence of receptors for bombesin/GRP and mRNA for three receptor subtypes in human ovarian epithelial cancers.Regul Pept. 2000 Jun 30;90(1-3):77-84. doi: 10.1016/s0167-0115(00)00114-2.
4 Peptide receptors as cancer drug targets.Ann N Y Acad Sci. 2019 Nov;1455(1):141-148. doi: 10.1111/nyas.14100. Epub 2019 May 10.
5 Rhodamine-marked bombesin: a novel means for prostate cancer fluorescence imaging.Invest New Drugs. 2014 Feb;32(1):37-46. doi: 10.1007/s10637-013-9975-2. Epub 2013 Jun 1.
6 Bombesin conjugated solid lipid nanoparticles for improved delivery of epigallocatechin gallate for breast cancer treatment.Chem Phys Lipids. 2019 Nov;224:104770. doi: 10.1016/j.chemphyslip.2019.04.005. Epub 2019 Apr 6.
7 HYNIC and DOMA conjugated radiolabeled bombesin analogs as receptor-targeted probes for scintigraphic detection of breast tumor.EJNMMI Res. 2019 Mar 18;9(1):25. doi: 10.1186/s13550-019-0493-x.
8 Large-scale delineation of secreted protein biomarkers overexpressed in cancer tissue and serum.Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3410-5. doi: 10.1073/pnas.0530278100. Epub 2003 Mar 6.
9 Expression of gastrin releasing Peptide receptor in renal cell carcinomas: a potential function for the regulation of neoangiogenesis and microvascular perfusion.J Urol. 2005 Jun;173(6):2154-9. doi: 10.1097/01.ju.0000158135.26893.bc.
10 BDNF/TrkB content and interaction with gastrin-releasing peptide receptor blockade in colorectal cancer.Oncology. 2010;79(5-6):430-9. doi: 10.1159/000326564. Epub 2011 Apr 8.
11 Over-expression of gastrin-releasing peptide in human esophageal squamous cell carcinomas.Carcinogenesis. 2004 Jun;25(6):865-71. doi: 10.1093/carcin/bgh097. Epub 2004 Feb 4.
12 Bombesin-mediated AP-1 activation in a human gastric cancer (SIIA).Surgery. 1996 Aug;120(2):130-6; discussion 136-7. doi: 10.1016/s0039-6060(96)80279-0.
13 Mechanisms of bombesin on growth of gastrinoma (PT) in vivo.Dig Dis Sci. 1996 Nov;41(11):2180-6. doi: 10.1007/BF02071398.
14 Gastrin-releasing peptide promotes the growth of HepG2 cells via EGFR-independent ERK1/2 activation.Oncol Rep. 2010 Aug;24(2):441-8. doi: 10.3892/or_00000877.
15 Aberrant activation of androgen receptor in a new neuropeptide-autocrine model of androgen-insensitive prostate cancer.Cancer Res. 2009 Jan 1;69(1):151-60. doi: 10.1158/0008-5472.CAN-08-0442.
16 Serum ProGRP and NSE levels predicting small cell lung cancer transformation in a patient with ALK rearrangement-positive non-small cell lung cancer: A case report.Oncol Lett. 2018 Oct;16(4):4219-4222. doi: 10.3892/ol.2018.9158. Epub 2018 Jul 17.
17 Augmented Responses to Ozone in Obese Mice Require IL-17A and Gastrin-Releasing Peptide.Am J Respir Cell Mol Biol. 2018 Mar;58(3):341-351. doi: 10.1165/rcmb.2017-0071OC.
18 Insights into the association of Gla-rich protein and osteoarthritis, novel splice variants and -carboxylation status.Mol Nutr Food Res. 2014 Aug;58(8):1636-46. doi: 10.1002/mnfr.201300941. Epub 2014 May 28.
19 Therapy of ovarian cancers with targeted cytotoxic analogs of bombesin, somatostatin, and luteinizing hormone-releasing hormone and their combinations.Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10403-10407. doi: 10.1073/pnas.0602971103. Epub 2006 Jun 26.
20 Design, Synthesis, and in Vitro and in Vivo Evaluation of High Affinity and Specificity Near-Infrared Fluorescent Bombesin Antagonists for Tumor Imaging.J Med Chem. 2018 Sep 13;61(17):7657-7670. doi: 10.1021/acs.jmedchem.8b00614. Epub 2018 Aug 27.
21 Midbrain Gene Screening Identifies a New Mesoaccumbal Glutamatergic Pathway and a Marker for Dopamine Cells Neuroprotected in Parkinson's Disease.Sci Rep. 2016 Oct 20;6:35203. doi: 10.1038/srep35203.
22 Physiological (68)Ga-RM2 uptake in patients with biochemically recurrent prostate cancer: an atlas of semi-quantitative measurements.Eur J Nucl Med Mol Imaging. 2020 Jan;47(1):115-122. doi: 10.1007/s00259-019-04503-4. Epub 2019 Sep 2.
23 Evaluation of a novel GRPR antagonist for prostate cancer PET imaging: [(64)Cu]-DOTHA(2)-PEG-RM26.Nucl Med Biol. 2018 Jan;56:31-38. doi: 10.1016/j.nucmedbio.2017.10.006. Epub 2017 Oct 23.
24 Paclitaxel-loaded nanobubble targeted to pro-gastrin-releasing peptide inhibits the growth of small cell lung cancer.Cancer Manag Res. 2019 Jul 16;11:6637-6649. doi: 10.2147/CMAR.S199175. eCollection 2019.
25 The Combination of the Tumor Markers Suggests the Histological Diagnosis of Lung Cancer.Biomed Res Int. 2017;2017:2013989. doi: 10.1155/2017/2013989. Epub 2017 May 18.
26 Prognostic markers in patients with typical bronchial carcinoid tumors.J Clin Endocrinol Metab. 2000 Sep;85(9):3425-30. doi: 10.1210/jcem.85.9.6785.
27 Independent prognostic genes and mechanism investigation for colon cancer.Biol Res. 2018 Apr 13;51(1):10. doi: 10.1186/s40659-018-0158-7.
28 SRC family kinases mediate epidermal growth factor receptor ligand cleavage, proliferation, and invasion of head and neck cancer cells.Cancer Res. 2004 Sep 1;64(17):6166-73. doi: 10.1158/0008-5472.CAN-04-0504.
29 Analysis of oncogenic activities of protein kinase D1 in head and neck squamous cell carcinoma.BMC Cancer. 2018 Nov 12;18(1):1107. doi: 10.1186/s12885-018-4965-6.
30 Neuropeptide gastrin-releasing peptide induces PI3K/reactive oxygen species-dependent migration in lung adenocarcinoma cells.Tumour Biol. 2017 Mar;39(3):1010428317694321. doi: 10.1177/1010428317694321.
31 Serum levels of osteoprotegerin (OPG) and pro gastrin releasing peptide (ProGRP) during chemotherapy of lung cancer.Rocz Akad Med Bialymst. 2004;49 Suppl 1:88-90.
32 Effective treatment of experimental U-87MG human glioblastoma in nude mice with a targeted cytotoxic bombesin analogue, AN-215.Br J Cancer. 2002 Apr 22;86(8):1322-7. doi: 10.1038/sj.bjc.6600235.
33 Extraintestinal roles of bombesin-like peptides and their receptors: lung.Curr Opin Endocrinol Diabetes Obes. 2013 Feb;20(1):22-6. doi: 10.1097/MED.0b013e32835bc368.
34 A Placebo-Controlled Crossover Trial of Gastrin-Releasing Peptide in Childhood Autism.Clin Neuropharmacol. 2017 May/Jun;40(3):108-112. doi: 10.1097/WNF.0000000000000213.
35 Expression and clinical value of gastrin-releasing peptide precursor in nephropathy and chronic kidney disease.Nephrology (Carlton). 2020 May;25(5):398-405. doi: 10.1111/nep.13642. Epub 2019 Aug 29.
36 Akt2 regulates metastatic potential in neuroblastoma.PLoS One. 2013;8(2):e56382. doi: 10.1371/journal.pone.0056382. Epub 2013 Feb 26.
37 Gastrin-releasing peptide and its receptor increase arthritis fibroblast-like synoviocytes invasiveness through activating the PI3K/AKT pathway.Peptides. 2017 Sep;95:57-61. doi: 10.1016/j.peptides.2017.07.008. Epub 2017 Jul 18.
38 Gastrin-releasing peptide receptor as a molecular target for psychiatric and neurological disorders.CNS Neurol Disord Drug Targets. 2006 Apr;5(2):197-204. doi: 10.2174/187152706776359673.
39 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
40 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
41 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
42 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.
43 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
44 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.