Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMNUJ15)

• DOT Name: EH domain-binding protein 1 (EHBP1)
• Gene Name: EHBP1
• Related Disease:
  Prostate carcinoma
  Nasopharyngeal carcinoma
  Prostate neoplasm
  Prostate cancer
• UniProt ID: EHBP1_HUMAN
• PDB ID: 2D89; 6ZSH; 6ZSI; 6ZSJ
• Pfam ID: PF12130 ; PF00307 ; PF10358
• Sequence:
  MASVWKRLQRVGKHASKFQFVASYQELMVECTKKWQPDKLVVVWTRRSRRKSSKAHSWQP
  GIKNPYRGVVVWPVPENIEITVTLFKDPHAEEFEDKEWTFVIENESPSGRRKALATSSIN
  MKQYASPMPTQTDVKLKFKPLSKKVVSAALQFSLSCIFLREGKATDEDMQSLASLMSMKQ
  ADIGNLDDFEEDNEDDDENRVNQEEKAAKITEIVNQLNALSSLDEDQDDCIKQANMRSAK
  SASSSEELINKLNFLDEAEKDLATVNSNPFDDPDAAELNPFGDPDSEEPITETASPRKTE
  DSFYNNSYNPFKEVQTPQYLNPFDEPEAFVTIKDSPPQSTKRKNIRPVDMSKYLYADSSK
  TEEEELDESNPFYEPKSTPPPNNLVNPVQELETERRVKRKAPAPPVLSPKTGVLNENTVS
  AGKDLSTSPKPSPIPSPVLGRKPNASQSLLVWCKEVTKNYRGVKITNFTTSWRNGLSFCA
  ILHHFRPDLIDYKSLNPQDIKENNKKAYDGFASIGISRLLEPSDMVLLAIPDKLTVMTYL
  YQIRAHFSGQELNVVQIEENSSKSTYKVGNYETDTNSSVDQEKFYAELSDLKREPELQQP
  ISGAVDFLSQDDSVFVNDSGVGESESEHQTPDDHLSPSTASPYCRRTKSDTEPQKSQQSS
  GRTSGSDDPGICSNTDSTQAQVLLGKKRLLKAETLELSDLYVSDKKKDMSPPFICEETDE
  QKLQTLDIGSNLEKEKLENSRSLECRSDPESPIKKTSLSPTSKLGYSYSRDLDLAKKKHA
  SLRQTESDPDADRTTLNHADHSSKIVQHRLLSRQEELKERARVLLEQARRDAALKAGNKH
  NTNTATPFCNRQLSDQQDEERRRQLRERARQLIAEARSGVKMSELPSYGEMAAEKLKERS
  KASGDENDNIEIDTNEEIPEGFVVGGGDELTNLENDLDTPEQNSKLVDLKLKKLLEVQPQ
  VANSPSSAAQKAVTESSEQDMKSGTEDLRTERLQKTTERFRNPVVFSKDSTVRKTQLQSF
  SQYIENRPEMKRQRSIQEDTKKGNEEKAAITETQRKPSEDEVLNKGFKDTSQYVVGELAA
  LENEQKQIDTRAALVEKRLRYLMDTGRNTEEEEAMMQEWFMLVNKKNALIRRMNQLSLLE
  KEHDLERRYELLNRELRAMLAIEDWQKTEAQKRREQLLLDELVALVNKRDALVRDLDAQE
  KQAEEEDEHLERTLEQNKGKMAKKEEKCVLQ
• Function: May play a role in actin reorganization. Links clathrin-mediated endocytosis to the actin cytoskeleton. May act as Rab effector protein and play a role in vesicle trafficking. Required for perinuclear sorting and insulin-regulated recycling of SLC2A4/GLUT4 in adipocytes.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate carcinoma	DISMJPLE	Definitive	Genetic Variation	[1]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Genetic Variation	[2]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[3]
Prostate cancer	DISF190Y	moderate	Biomarker	[4]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Malathion	DMXZ84M	Approved	EH domain-binding protein 1 (EHBP1) increases the response to substance of Malathion.	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of EH domain-binding protein 1 (EHBP1).	[5]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of EH domain-binding protein 1 (EHBP1).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of EH domain-binding protein 1 (EHBP1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of EH domain-binding protein 1 (EHBP1).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of EH domain-binding protein 1 (EHBP1).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of EH domain-binding protein 1 (EHBP1).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of EH domain-binding protein 1 (EHBP1).	[10]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of EH domain-binding protein 1 (EHBP1).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of EH domain-binding protein 1 (EHBP1).	[12]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of EH domain-binding protein 1 (EHBP1).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of EH domain-binding protein 1 (EHBP1).	[14]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of EH domain-binding protein 1 (EHBP1).	[15]
Selenium	DM25CGV	Approved	Selenium decreases the expression of EH domain-binding protein 1 (EHBP1).	[16]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of EH domain-binding protein 1 (EHBP1).	[17]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of EH domain-binding protein 1 (EHBP1).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of EH domain-binding protein 1 (EHBP1).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of EH domain-binding protein 1 (EHBP1).	[18]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of EH domain-binding protein 1 (EHBP1).	[19]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of EH domain-binding protein 1 (EHBP1).	[20]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of EH domain-binding protein 1 (EHBP1).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of EH domain-binding protein 1 (EHBP1).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of EH domain-binding protein 1 (EHBP1).	[23]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of EH domain-binding protein 1 (EHBP1).	[24]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of EH domain-binding protein 1 (EHBP1).	[26]

References

• [1] Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.Nat Genet. 2018 Jul;50(7):928-936. doi: 10.1038/s41588-018-0142-8. Epub 2018 Jun 11.
• [2] A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci.Nat Genet. 2010 Jul;42(7):599-603. doi: 10.1038/ng.601. Epub 2010 May 30.
• [3] Genetic susceptibility loci, pesticide exposure and prostate cancer risk. PLoS One. 2013 Apr 4;8(4):e58195. doi: 10.1371/journal.pone.0058195. Print 2013.
• [4] Systematic meta-analyses of gene-specific genetic association studies in prostate cancer.Oncotarget. 2016 Apr 19;7(16):22271-84. doi: 10.18632/oncotarget.7926.
• [5] 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.
• [6] 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.
• [7] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [8] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [9] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [10] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [11] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [12] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [13] 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.
• [14] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [15] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [16] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [17] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [18] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [19] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [20] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [21] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [22] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [23] 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.
• [24] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [25] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [26] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.
• [27] Genetic susceptibility loci, pesticide exposure and prostate cancer risk. PLoS One. 2013 Apr 4;8(4):e58195. doi: 10.1371/journal.pone.0058195. Print 2013.