Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEB0ROY)

DOT Name G-protein coupled receptor 42 (GPR42)
Gene Name GPR42
Related Disease
Epithelial ovarian cancer ( )
Melanoma ( )
Acute myelogenous leukaemia ( )
Advanced cancer ( )
Alzheimer disease ( )
Anxiety ( )
Anxiety disorder ( )
Arteriosclerosis ( )
Asthma ( )
Atherosclerosis ( )
Attention deficit hyperactivity disorder ( )
Autoimmune disease ( )
Breast cancer ( )
Breast carcinoma ( )
Cardiac failure ( )
Colon cancer ( )
Colon carcinoma ( )
Hepatocellular carcinoma ( )
High blood pressure ( )
Kaposi sarcoma ( )
Lung cancer ( )
Lung carcinoma ( )
Metabolic disorder ( )
Metastatic malignant neoplasm ( )
Multiple sclerosis ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
Non-small-cell lung cancer ( )
Obesity ( )
Osteoporosis ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Prostate cancer ( )
Prostate carcinoma ( )
Rheumatoid arthritis ( )
Schizophrenia ( )
Type-1/2 diabetes ( )
Uveal Melanoma ( )
Cardiovascular disease ( )
Colorectal carcinoma ( )
Gastric cancer ( )
Glioma ( )
Stomach cancer ( )
Adult glioblastoma ( )
Congestive heart failure ( )
Depression ( )
Endometrial carcinoma ( )
Glioblastoma multiforme ( )
Myocardial infarction ( )
Pancreatic cancer ( )
UniProt ID
GPR42_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00001
Sequence
MDTGPDQSYFSGNHWFVFSVYLLTFLVGLPLNLLALVVFVGKLRCRPVAVDVLLLNLTAS
DLLLLLFLPFRMVEAANGMHWPLPFILCPLSGFIFFTTIYLTALFLAAVSIERFLSVAHP
LWYKTRPRLGQAGLVSVACWLLASAHCSVVYVIEFSGDISHSQGTNGTCYLEFRKDQLAI
LLPVRLEMAVVLFVVPLIITSYCYSRLVWILGRGGSHRRQRRVAGLVAATLLNFLVCFGP
YNVSHVVGYICGESPVWRIYVTLLSTLNSCVDPFVYYFSSSGFQADFHELLRRLCGLWGQ
WQQESSMELKEQKGGEEQRADRPAERKTSEHSQGCGTGGQVACAEN
Function
G protein-coupled receptor that is activated by short chain fatty acids (SCFAs), such as propionate. Hence may play a role in the regulation of whole-body energy homeostasis and/or in intestinal immunity.

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Epithelial ovarian cancer DIS56MH2 Definitive Biomarker [1]
Melanoma DIS1RRCY Definitive Altered Expression [2]
Acute myelogenous leukaemia DISCSPTN Strong Biomarker [3]
Advanced cancer DISAT1Z9 Strong Biomarker [4]
Alzheimer disease DISF8S70 Strong Biomarker [5]
Anxiety DISIJDBA Strong Biomarker [6]
Anxiety disorder DISBI2BT Strong Biomarker [6]
Arteriosclerosis DISK5QGC Strong Biomarker [7]
Asthma DISW9QNS Strong Biomarker [8]
Atherosclerosis DISMN9J3 Strong Biomarker [7]
Attention deficit hyperactivity disorder DISL8MX9 Strong Genetic Variation [9]
Autoimmune disease DISORMTM Strong Biomarker [10]
Breast cancer DIS7DPX1 Strong Biomarker [11]
Breast carcinoma DIS2UE88 Strong Biomarker [11]
Cardiac failure DISDC067 Strong Biomarker [12]
Colon cancer DISVC52G Strong Biomarker [13]
Colon carcinoma DISJYKUO Strong Biomarker [13]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [14]
High blood pressure DISY2OHH Strong Biomarker [15]
Kaposi sarcoma DISC1H1Z Strong Biomarker [16]
Lung cancer DISCM4YA Strong Biomarker [17]
Lung carcinoma DISTR26C Strong Biomarker [17]
Metabolic disorder DIS71G5H Strong Biomarker [18]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [19]
Multiple sclerosis DISB2WZI Strong Genetic Variation [20]
Neoplasm DISZKGEW Strong Biomarker [21]
Non-insulin dependent diabetes DISK1O5Z Strong Biomarker [22]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [23]
Obesity DIS47Y1K Strong Biomarker [24]
Osteoporosis DISF2JE0 Strong Biomarker [25]
Ovarian cancer DISZJHAP Strong Biomarker [26]
Ovarian neoplasm DISEAFTY Strong Biomarker [26]
Prostate cancer DISF190Y Strong Altered Expression [27]
Prostate carcinoma DISMJPLE Strong Altered Expression [27]
Rheumatoid arthritis DISTSB4J Strong Biomarker [28]
Schizophrenia DISSRV2N Strong Biomarker [29]
Type-1/2 diabetes DISIUHAP Strong Biomarker [30]
Uveal Melanoma DISA7ZGL Strong Genetic Variation [31]
Cardiovascular disease DIS2IQDX moderate Biomarker [12]
Colorectal carcinoma DIS5PYL0 moderate Biomarker [32]
Gastric cancer DISXGOUK moderate Biomarker [33]
Glioma DIS5RPEH moderate Biomarker [34]
Stomach cancer DISKIJSX moderate Biomarker [33]
Adult glioblastoma DISVP4LU Disputed Genetic Variation [35]
Congestive heart failure DIS32MEA Disputed Biomarker [36]
Depression DIS3XJ69 Limited Biomarker [37]
Endometrial carcinoma DISXR5CY Limited Altered Expression [38]
Glioblastoma multiforme DISK8246 Limited Biomarker [39]
Myocardial infarction DIS655KI Limited Altered Expression [40]
Pancreatic cancer DISJC981 Limited Biomarker [41]
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⏷ Show the Full List of 50 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
Valproate DMCFE9I Approved Valproate increases the methylation of G-protein coupled receptor 42 (GPR42). [42]
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1 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of G-protein coupled receptor 42 (GPR42). [43]
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References

1 Association of metastin/a G-protein-coupled receptor signaling and Down syndrome critical region 1 in epithelial ovarian cancer.Anticancer Res. 2009 Feb;29(2):617-23.
2 MC1R CpG island regulates MC1R expression and is methylated in a subset of melanoma tumours.Pigment Cell Melanoma Res. 2019 Mar;32(2):320-325. doi: 10.1111/pcmr.12739. Epub 2018 Oct 18.
3 An Overview on G Protein-coupled Receptor-induced Signal Transduction in Acute Myeloid Leukemia.Curr Med Chem. 2019;26(28):5293-5316. doi: 10.2174/0929867326666190429153247.
4 Conjugable A(3) adenosine receptor antagonists for the development of functionalized ligands and their use in fluorescent probes.Eur J Med Chem. 2020 Jan 15;186:111886. doi: 10.1016/j.ejmech.2019.111886. Epub 2019 Nov 22.
5 Role of APP Interactions with Heterotrimeric G Proteins: Physiological Functions and Pathological Consequences.Front Mol Neurosci. 2017 Jan 31;10:3. doi: 10.3389/fnmol.2017.00003. eCollection 2017.
6 RGS2 ggenetic variation: association analysis with panic disorder and dimensional as well as intermediate phenotypes of anxiety.Am J Med Genet B Neuropsychiatr Genet. 2015 Apr;168B(3):211-22. doi: 10.1002/ajmg.b.32299. Epub 2015 Mar 4.
7 Towards Targeting the Urotensinergic System: Overview and Challenges.Trends Pharmacol Sci. 2019 Oct;40(10):725-734. doi: 10.1016/j.tips.2019.08.005. Epub 2019 Sep 6.
8 Inflammatory mediators mediate airway smooth muscle contraction through a G protein-coupled receptor-transmembrane protein 16A-voltage-dependent Ca(2+) channel axis and contribute to bronchial hyperresponsiveness in asthma.J Allergy Clin Immunol. 2018 Apr;141(4):1259-1268.e11. doi: 10.1016/j.jaci.2017.05.053. Epub 2017 Jul 25.
9 Interaction effects of GIT1 and DRD4 gene variants on continuous performance test variables in patients with ADHD.Brain Behav. 2017 Aug 1;7(9):e00785. doi: 10.1002/brb3.785. eCollection 2017 Sep.
10 Characterization, Dynamics, and Mechanism of CXCR4 Antagonists on a Constitutively Active Mutant.Cell Chem Biol. 2019 May 16;26(5):662-673.e7. doi: 10.1016/j.chembiol.2019.01.012. Epub 2019 Feb 28.
11 Human G protein-coupled receptor 30 is N-glycosylated and N-terminal domain asparagine 44 is required for receptor structure and activity.Biosci Rep. 2019 Feb 26;39(2):BSR20182436. doi: 10.1042/BSR20182436. Print 2019 Feb 28.
12 The apelinergic system: a perspective on challenges and opportunities in cardiovascular and metabolic disorders.Ann N Y Acad Sci. 2019 Nov;1455(1):12-33. doi: 10.1111/nyas.14123. Epub 2019 Jun 25.
13 G protein-coupled receptor LGR6 is an independent risk factor for colon adenocarcinoma.Front Med. 2019 Aug;13(4):482-491. doi: 10.1007/s11684-018-0633-0. Epub 2018 Jul 4.
14 CD97 Promotes Tumor Aggressiveness Through the Traditional G Protein-Coupled Receptor-Mediated Signaling in Hepatocellular Carcinoma.Hepatology. 2018 Nov;68(5):1865-1878. doi: 10.1002/hep.30068. Epub 2018 Sep 22.
15 Differential regulation of (2)-adrenoceptor and adenosine A(2B) receptor signalling by GRK and arrestin proteins in arterial smooth muscle.Cell Signal. 2018 Nov;51:86-98. doi: 10.1016/j.cellsig.2018.07.013. Epub 2018 Jul 31.
16 In vitro studies revealed a downregulation of Wnt/-catenin cascade by active vitamin D and TX 527 analog in a Kaposi's sarcoma cellular model.Toxicol In Vitro. 2020 Mar;63:104748. doi: 10.1016/j.tiv.2019.104748. Epub 2019 Dec 12.
17 Protease-activated receptor 2 induces migration and promotes Slug-mediated epithelial-mesenchymal transition in lung adenocarcinoma cells.Biochim Biophys Acta Mol Cell Res. 2019 Mar;1866(3):486-503. doi: 10.1016/j.bbamcr.2018.10.011. Epub 2018 Oct 13.
18 Evaluation of novel TGR5 agonist in combination with Sitagliptin for possible treatment of type 2 diabetes.Bioorg Med Chem Lett. 2018 Jun 1;28(10):1849-1852. doi: 10.1016/j.bmcl.2018.04.011. Epub 2018 Apr 5.
19 Quantitative phosphoproteomic analysis reveals system-wide signaling pathways downstream of SDF-1/CXCR4 in breast cancer stem cells.Proc Natl Acad Sci U S A. 2014 May 27;111(21):E2182-90. doi: 10.1073/pnas.1404943111. Epub 2014 Apr 29.
20 A non-functional galanin receptor-2 in a multiple sclerosis patient.Pharmacogenomics J. 2019 Feb;19(1):72-82. doi: 10.1038/s41397-018-0032-6. Epub 2018 Aug 22.
21 Cryo-EM structure of oxysterol-bound human Smoothened coupled to a heterotrimeric G(i).Nature. 2019 Jul;571(7764):279-283. doi: 10.1038/s41586-019-1286-0. Epub 2019 Jun 5.
22 Phase-plate cryo-EM structure of a biased agonist-bound human GLP-1 receptor-Gs complex.Nature. 2018 Mar 1;555(7694):121-125. doi: 10.1038/nature25773. Epub 2018 Feb 21.
23 Genetic Modifiers of Progression-Free Survival in Never-Smoking Lung Adenocarcinoma Patients Treated with First-Line Tyrosine Kinase Inhibitors.Am J Respir Crit Care Med. 2017 Mar 1;195(5):663-673. doi: 10.1164/rccm.201602-0300OC.
24 Human Gain-of-Function MC4R Variants Show Signaling Bias and Protect against Obesity.Cell. 2019 Apr 18;177(3):597-607.e9. doi: 10.1016/j.cell.2019.03.044.
25 Structure and dynamics of the active human parathyroid hormone receptor-1.Science. 2019 Apr 12;364(6436):148-153. doi: 10.1126/science.aav7942.
26 Luteinizing hormone-induced up-regulation of ErbB-2 is insufficient stimulant of growth and invasion in ovarian cancer cells.Mol Cancer Res. 2008 Nov;6(11):1775-85. doi: 10.1158/1541-7786.MCR-08-0214.
27 Positron Emission Tomography Imaging of the Gastrin-Releasing Peptide Receptor with a Novel Bombesin Analogue.ACS Omega. 2019 Jan 31;4(1):1470-1478. doi: 10.1021/acsomega.8b03293. Epub 2019 Jan 16.
28 Increased expression of G-protein-coupled receptor kinases 3 and 4 in hyperfunctioning thyroid nodules.J Endocrinol. 2004 Jul;182(1):173-82. doi: 10.1677/joe.0.1820173.
29 Risk gene-set and pathways in 22q11.2 deletion-related schizophrenia: a genealogical molecular approach.Transl Psychiatry. 2019 Jan 17;9(1):15. doi: 10.1038/s41398-018-0354-9.
30 Lentivirusmediated overexpression of CD97/ADGRE5 reverses dysregulated high glucoseinduced endothelial cell migration.Mol Med Rep. 2017 May;15(5):3048-3054. doi: 10.3892/mmr.2017.6417. Epub 2017 Mar 30.
31 Atypical activation of the G protein G(q) by the oncogenic mutation Q209P.J Biol Chem. 2018 Dec 21;293(51):19586-19599. doi: 10.1074/jbc.RA118.005291. Epub 2018 Oct 23.
32 G protein-coupled receptor GPR55 promotes colorectal cancer and has opposing effects to cannabinoid receptor 1.Int J Cancer. 2018 Jan 1;142(1):121-132. doi: 10.1002/ijc.31030. Epub 2017 Sep 21.
33 MicroRNA-760 acts as a tumor suppressor in gastric cancer development via inhibiting G-protein-coupled receptor kinase interacting protein-1 transcription.World J Gastroenterol. 2019 Dec 7;25(45):6619-6633. doi: 10.3748/wjg.v25.i45.6619.
34 Clinicopathological and prognostic significance of aberrant G protein-couple receptor 110 (GPR110) expression in gastric cancer.Pathol Res Pract. 2019 Mar;215(3):539-545. doi: 10.1016/j.prp.2018.12.004. Epub 2018 Dec 6.
35 PREX1 integrates G protein-coupled receptor and phosphoinositide 3-kinase signaling to promote glioblastoma invasion.Oncotarget. 2017 Jan 31;8(5):8559-8573. doi: 10.18632/oncotarget.14348.
36 Molecular signaling of G-protein-coupled receptor in chronic heart failure and associated complications.Drug Dev Res. 2020 Feb;81(1):23-31. doi: 10.1002/ddr.21627. Epub 2019 Nov 30.
37 A high-fat diet promotes depression-like behavior in mice by suppressing hypothalamic PKA signaling.Transl Psychiatry. 2019 May 10;9(1):141. doi: 10.1038/s41398-019-0470-1.
38 The G protein-coupled receptor GPR30 mediates the nontranscriptional effect of estrogen on the activation of PI3K/Akt pathway in endometrial cancer cells.Int J Gynecol Cancer. 2013 Jan;23(1):52-9. doi: 10.1097/IGC.0b013e31827912b8.
39 C1q/TNF-related peptide 8 (CTRP8) promotes temozolomide resistance in human glioblastoma.Mol Oncol. 2018 Sep;12(9):1464-1479. doi: 10.1002/1878-0261.12349. Epub 2018 Aug 2.
40 Endothelin-1 promotes hypertrophic remodelling of cardiac myocytes by activating sustained signalling and transcription downstream of endothelin type A receptors.Cell Signal. 2017 Aug;36:240-254. doi: 10.1016/j.cellsig.2017.04.010. Epub 2017 Apr 13.
41 Regulatory Role of G Protein-coupled Receptors in Pancreatic Cancer Development and Progression.Curr Med Chem. 2018;25(22):2566-2575. doi: 10.2174/0929867324666170303121708.
42 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
43 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.