Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOI2NYG)

DOT Name Inhibin beta E chain (INHBE)
Synonyms Activin beta-E chain
Gene Name INHBE
Related Disease
Non-insulin dependent diabetes ( )
Gout ( )
Lysosomal lipid storage disorder ( )
UniProt ID
INHBE_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00019
Sequence
MRLPDVQLWLVLLWALVRAQGTGSVCPSCGGSKLAPQAERALVLELAKQQILDGLHLTSR
PRITHPPPQAALTRALRRLQPGSVAPGNGEEVISFATVTDSTSAYSSLLTFHLSTPRSHH
LYHARLWLHVLPTLPGTLCLRIFRWGPRRRRQGSRTLLAEHHITNLGWHTLTLPSSGLRG
EKSGVLKLQLDCRPLEGNSTVTGQPRRLLDTAGHQQPFLELKIRANEPGAGRARRRTPTC
EPATPLCCRRDHYVDFQELGWRDWILQPEGYQLNYCSGQCPPHLAGSPGIAASFHSAVFS
LLKANNPWPASTSCCVPTARRPLSLLYLDHNGNVVKTDVPDMVVEACGCS
Function
Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythroid differentiation, insulin secretion, nerve cell survival, embryonic axial development or bone growth, depending on their subunit composition. Inhibins appear to oppose the functions of activins.
KEGG Pathway
Cytokine-cytokine receptor interaction (hsa04060 )
TGF-beta sig.ling pathway (hsa04350 )
Sig.ling pathways regulating pluripotency of stem cells (hsa04550 )
Reactome Pathway
Glycoprotein hormones (R-HSA-209822 )

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Non-insulin dependent diabetes DISK1O5Z Definitive Altered Expression [1]
Gout DISHC0U7 Strong Genetic Variation [2]
Lysosomal lipid storage disorder DISXQRTX Limited Biomarker [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
58 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 Inhibin beta E chain (INHBE). [4]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Inhibin beta E chain (INHBE). [5]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Inhibin beta E chain (INHBE). [3]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of Inhibin beta E chain (INHBE). [7]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Inhibin beta E chain (INHBE). [8]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Inhibin beta E chain (INHBE). [9]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Inhibin beta E chain (INHBE). [10]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Inhibin beta E chain (INHBE). [11]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Inhibin beta E chain (INHBE). [12]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Inhibin beta E chain (INHBE). [7]
Marinol DM70IK5 Approved Marinol decreases the expression of Inhibin beta E chain (INHBE). [13]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Inhibin beta E chain (INHBE). [14]
Phenobarbital DMXZOCG Approved Phenobarbital increases the expression of Inhibin beta E chain (INHBE). [3]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Inhibin beta E chain (INHBE). [15]
Demecolcine DMCZQGK Approved Demecolcine increases the expression of Inhibin beta E chain (INHBE). [16]
Niclosamide DMJAGXQ Approved Niclosamide increases the expression of Inhibin beta E chain (INHBE). [17]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of Inhibin beta E chain (INHBE). [18]
Hydroquinone DM6AVR4 Approved Hydroquinone decreases the expression of Inhibin beta E chain (INHBE). [19]
Rosiglitazone DMILWZR Approved Rosiglitazone decreases the expression of Inhibin beta E chain (INHBE). [18]
Clozapine DMFC71L Approved Clozapine increases the expression of Inhibin beta E chain (INHBE). [20]
Ethinyl estradiol DMODJ40 Approved Ethinyl estradiol affects the expression of Inhibin beta E chain (INHBE). [21]
Haloperidol DM96SE0 Approved Haloperidol increases the expression of Inhibin beta E chain (INHBE). [3]
Fluoxetine DM3PD2C Approved Fluoxetine increases the expression of Inhibin beta E chain (INHBE). [20]
Sertraline DM0FB1J Approved Sertraline increases the expression of Inhibin beta E chain (INHBE). [20]
Bosentan DMIOGBU Approved Bosentan affects the expression of Inhibin beta E chain (INHBE). [22]
Isoniazid DM5JVS3 Approved Isoniazid increases the expression of Inhibin beta E chain (INHBE). [3]
Tetracycline DMZA017 Approved Tetracycline increases the expression of Inhibin beta E chain (INHBE). [3]
Thioridazine DM35M8J Approved Thioridazine increases the expression of Inhibin beta E chain (INHBE). [20]
Imipramine DM2NUH3 Approved Imipramine increases the expression of Inhibin beta E chain (INHBE). [20]
Nelfinavir mesylate DMFX6G8 Approved Nelfinavir mesylate increases the expression of Inhibin beta E chain (INHBE). [23]
Clomipramine DMINRKW Approved Clomipramine increases the expression of Inhibin beta E chain (INHBE). [20]
Citalopram DM2G9AE Approved Citalopram increases the expression of Inhibin beta E chain (INHBE). [24]
Erythromycin DM4K7GQ Approved Erythromycin increases the expression of Inhibin beta E chain (INHBE). [3]
Loratadine DMF3AN7 Approved Loratadine increases the expression of Inhibin beta E chain (INHBE). [20]
Pentamidine DMHZJCG Approved Pentamidine increases the expression of Inhibin beta E chain (INHBE). [20]
Quinidine DMLPICK Approved Quinidine increases the expression of Inhibin beta E chain (INHBE). [20]
Flecainide DMSQDLE Approved Flecainide increases the expression of Inhibin beta E chain (INHBE). [20]
Perhexiline DMINO7Z Approved Perhexiline increases the expression of Inhibin beta E chain (INHBE). [3]
Clarithromycin DM4M1SG Approved Clarithromycin increases the expression of Inhibin beta E chain (INHBE). [20]
Doxepin DMPI98T Approved Doxepin increases the expression of Inhibin beta E chain (INHBE). [24]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Inhibin beta E chain (INHBE). [25]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Inhibin beta E chain (INHBE). [15]
Chlorpromazine DMBGZI3 Phase 3 Trial Chlorpromazine increases the expression of Inhibin beta E chain (INHBE). [20]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of Inhibin beta E chain (INHBE). [26]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of Inhibin beta E chain (INHBE). [20]
OTX-015 DMI8RG1 Phase 1/2 OTX-015 decreases the expression of Inhibin beta E chain (INHBE). [27]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Inhibin beta E chain (INHBE). [8]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Inhibin beta E chain (INHBE). [27]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Inhibin beta E chain (INHBE). [28]
Mivebresib DMCPF90 Phase 1 Mivebresib decreases the expression of Inhibin beta E chain (INHBE). [27]
Chlorcyclizine DM3L52Q Phase 1 Chlorcyclizine increases the expression of Inhibin beta E chain (INHBE). [20]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Inhibin beta E chain (INHBE). [29]
ZIMELIDINE DMNI3U2 Withdrawn from market ZIMELIDINE increases the expression of Inhibin beta E chain (INHBE). [20]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN increases the expression of Inhibin beta E chain (INHBE). [23]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Inhibin beta E chain (INHBE). [30]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Inhibin beta E chain (INHBE). [16]
OXYQUINOLINE DMZVS9Y Investigative OXYQUINOLINE decreases the expression of Inhibin beta E chain (INHBE). [9]
1,4-Dithiothreitol DMIFOXE Investigative 1,4-Dithiothreitol increases the expression of Inhibin beta E chain (INHBE). [23]
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⏷ Show the Full List of 58 Drug(s)

References

1 Inhibin E (INHBE) is a possible insulin resistance-associated hepatokine identified by comprehensive gene expression analysis in human liver biopsy samples.PLoS One. 2018 Mar 29;13(3):e0194798. doi: 10.1371/journal.pone.0194798. eCollection 2018.
2 Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet. 2013 Feb;45(2):145-54. doi: 10.1038/ng.2500. Epub 2012 Dec 23.
3 Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells. Toxicol Sci. 2007 Mar;96(1):101-14.
4 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.
5 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
6 Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells. Toxicol Sci. 2007 Mar;96(1):101-14.
7 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
8 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
9 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
10 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
11 Gene expression profile induced by arsenic trioxide in chronic lymphocytic leukemia cells reveals a central role for heme oxygenase-1 in apoptosis and regulation of matrix metalloproteinase-9. Oncotarget. 2016 Dec 13;7(50):83359-83377.
12 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
13 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
14 The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
15 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.
16 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
17 Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
18 Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
19 Differently expressed long noncoding RNAs and mRNAs in TK6 cells exposed to low dose hydroquinone. Oncotarget. 2017 Oct 4;8(56):95554-95567. doi: 10.18632/oncotarget.21481. eCollection 2017 Nov 10.
20 A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system. Toxicol Sci. 2005 Feb;83(2):282-92.
21 The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.
22 Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
23 Inhibin beta E is upregulated by drug-induced endoplasmic reticulum stress as a transcriptional target gene of ATF4. Toxicol Appl Pharmacol. 2012 Oct 15;264(2):300-4. doi: 10.1016/j.taap.2012.08.011. Epub 2012 Aug 23.
24 In vitro detection of drug-induced phospholipidosis using gene expression and fluorescent phospholipid based methodologies. Toxicol Sci. 2007 Sep;99(1):162-73.
25 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
26 Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
27 Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
28 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
29 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
30 Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.