Details of Drug Off-Target (DOT)

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

• DOT Name: Heme-binding protein 2 (HEBP2)
• Synonyms: Placental protein 23; PP23; Protein SOUL
• Gene Name: HEBP2
• Related Disease:
  Advanced cancer
  Lung cancer
  Lung carcinoma
  Liver cancer
• UniProt ID: HEBP2_HUMAN
• PDB ID: 3R85; 3R8J; 3R8K; 4AYZ; 4B0Y; 5GQQ
• Pfam ID: PF04832
• Sequence:
  MAEPLQPDPGAAEDAAAQAVETPGWKAPEDAGPQPGSYEIRHYGPAKWVSTSVESMDWDS
  AIQTGFTKLNSYIQGKNEKEMKIKMTAPVTSYVEPGSGPFSESTITISLYIPSEQQFDPP
  RPLESDVFIEDRAEMTVFVRSFDGFSSAQKNQEQLLTLASILREDGKVFDEKVYYTAGYN
  SPVKLLNRNNEVWLIQKNEPTKENE
• Function: Can promote mitochondrial permeability transition and facilitate necrotic cell death under different types of stress conditions.
• Tissue Specificity: Detected in placenta.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[1]
Lung cancer	DISCM4YA	Definitive	Altered Expression	[1]
Lung carcinoma	DISTR26C	Definitive	Altered Expression	[1]
Liver cancer	DISDE4BI	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Heme-binding protein 2 (HEBP2).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Heme-binding protein 2 (HEBP2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Heme-binding protein 2 (HEBP2).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Heme-binding protein 2 (HEBP2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Heme-binding protein 2 (HEBP2).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heme-binding protein 2 (HEBP2).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Heme-binding protein 2 (HEBP2).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Heme-binding protein 2 (HEBP2).	[10]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Heme-binding protein 2 (HEBP2).	[11]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Heme-binding protein 2 (HEBP2).	[12]
Isoflavone	DM7U58J	Phase 4	Isoflavone decreases the expression of Heme-binding protein 2 (HEBP2).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Heme-binding protein 2 (HEBP2).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Heme-binding protein 2 (HEBP2).	[17]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Heme-binding protein 2 (HEBP2).	[18]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Heme-binding protein 2 (HEBP2).	[19]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Heme-binding protein 2 (HEBP2).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Heme-binding protein 2 (HEBP2).	[16]

References

• [1] Deregulated ALG-2/HEBP2 axis alters microtubule dynamics and mitotic spindle behavior to stimulate cancer development.J Cell Physiol. 2017 Nov;232(11):3067-3076. doi: 10.1002/jcp.25754. Epub 2017 Mar 1.
• [2] Genomic models of short-term exposure accurately predict long-term chemical carcinogenicity and identify putative mechanisms of action.PLoS One. 2014 Jul 24;9(7):e102579. doi: 10.1371/journal.pone.0102579. eCollection 2014.
• [3] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] Differential protein expression of peroxiredoxin I and II by benzo(a)pyrene and quercetin treatment in 22Rv1 and PrEC prostate cell lines. Toxicol Appl Pharmacol. 2007 Apr 15;220(2):197-210. doi: 10.1016/j.taap.2006.12.030. Epub 2007 Jan 9.
• [10] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] 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.
• [13] Soy isoflavones exert differential effects on androgen responsive genes in LNCaP human prostate cancer cells. J Nutr. 2007 Apr;137(4):964-72.
• [14] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [15] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [16] 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.
• [17] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [18] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [19] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.