Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR9MPDX)

• DOT Name: Heme-binding protein 1 (HEBP1)
• Synonyms: p22HBP
• Gene Name: HEBP1
• Related Disease:
  Non-insulin dependent diabetes
  Abscess
  Alzheimer disease
  Bacterial meningitis
  Breast cancer
  Chronic obstructive pulmonary disease
  Congestive heart failure
  Diabetic kidney disease
  Fatty liver disease
  Intrahepatic cholangiocarcinoma
  Bacterial infection
  Hepatocellular carcinoma
  Prostate cancer
• UniProt ID: HEBP1_HUMAN
• Pfam ID: PF04832
• Sequence:
  MLGMIKNSLFGSVETWPWQVLSKGDKEEVAYEERACEGGKFATVEVTDKPVDEALREAMP
  KVAKYAGGTNDKGIGMGMTVPISFAVFPNEDGSLQKKLKVWFRIPNQFQSDPPAPSDKSV
  KIEEREGITVYSMQFGGYAKEADYVAQATRLRAALEGTATYRGDIYFCTGYDPPMKPYGR
  RNEIWLLKT
• Function: May bind free porphyrinogens that may be present in the cell and thus facilitate removal of these potentially toxic compound. Binds with a high affinity to one molecule of heme or porphyrins. It binds metalloporphyrins, free porphyrins and N-methylprotoporphyrin with similar affinities.
• Reactome Pathway:
  Formyl peptide receptors bind formyl peptides and many other ligands (R-HSA-444473)
  G alpha (i) signalling events (R-HSA-418594)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[1]
Abscess	DISAP982	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[3]
Bacterial meningitis	DISRP9SL	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Biomarker	[6]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[6]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[7]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[8]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Biomarker	[9]
Bacterial infection	DIS5QJ9S	moderate	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[11]
Prostate cancer	DISF190Y	moderate	Altered Expression	[12]

11 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 1 (HEBP1).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Heme-binding protein 1 (HEBP1).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Heme-binding protein 1 (HEBP1).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Heme-binding protein 1 (HEBP1).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Heme-binding protein 1 (HEBP1).	[17]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Heme-binding protein 1 (HEBP1).	[18]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heme-binding protein 1 (HEBP1).	[19]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Heme-binding protein 1 (HEBP1).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Heme-binding protein 1 (HEBP1).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Heme-binding protein 1 (HEBP1).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Heme-binding protein 1 (HEBP1).	[23]

References

• [1] Isolated high home systolic blood pressure in patients with type 2 diabetes is a prognostic factor for the development of diabetic nephropathy: KAMOGAWA-HBP study.Diabetes Res Clin Pract. 2019 Dec;158:107920. doi: 10.1016/j.diabres.2019.107920. Epub 2019 Nov 8.
• [2] Escherichia coli hemoglobin protease autotransporter contributes to synergistic abscess formation and heme-dependent growth of Bacteroides fragilis.Infect Immun. 2002 Jan;70(1):5-10. doi: 10.1128/IAI.70.1.5-10.2002.
• [3] The Healthy Brain Project: An Online Platform for the Recruitment, Assessment, and Monitoring of Middle-Aged Adults at Risk of Developing Alzheimer's Disease.J Alzheimers Dis. 2019;68(3):1211-1228. doi: 10.3233/JAD-181139.
• [4] Accuracy of heparin binding protein: as a new marker in prediction of acute bacterial meningitis.Braz J Microbiol. 2018 Nov;49 Suppl 1(Suppl 1):213-219. doi: 10.1016/j.bjm.2018.05.007. Epub 2018 Aug 17.
• [5] Enhanced hexosamine metabolism drives metabolic and signaling networks involving hyaluronan production and O-GlcNAcylation to exacerbate breast cancer.Cell Death Dis. 2019 Oct 23;10(11):803. doi: 10.1038/s41419-019-2034-y.
• [6] Home-based telerehabilitation in older patients with chronic obstructive pulmonary disease and heart failure: a randomised controlled trial.Age Ageing. 2018 Jan 1;47(1):82-88. doi: 10.1093/ageing/afx146.
• [7] Maximum morning home systolic blood pressure is an indicator of the development of diabetic nephropathy: The KAMOGAWA-HBP study.J Diabetes Investig. 2019 Nov;10(6):1543-1549. doi: 10.1111/jdi.13040. Epub 2019 May 7.
• [8] Iso- or hyperintensity of hepatocellular adenomas on hepatobiliary phase does not always correspond to hepatospecific contrast-agent uptake: importance for tumor subtyping.Eur Radiol. 2019 Jul;29(7):3791-3801. doi: 10.1007/s00330-019-06150-7. Epub 2019 Apr 1.
• [9] Differentiation between inflammatory myofibroblastic tumor and cholangiocarcinoma manifesting as target appearance on gadoxetic acid-enhanced MRI.Abdom Radiol (NY). 2019 Apr;44(4):1395-1406. doi: 10.1007/s00261-018-1847-y.
• [10] Heparin-binding protein: a key player in the pathophysiology of organ dysfunction in sepsis.J Intern Med. 2017 Jun;281(6):562-574. doi: 10.1111/joim.12604. Epub 2017 Mar 28.
• [11] LI-RADS v2014 categorization of hepatocellular carcinoma: Intraindividual comparison between gadopentetate dimeglumine-enhanced MRI and gadoxetic acid-enhanced MRI.Eur Radiol. 2019 Jan;29(1):401-410. doi: 10.1007/s00330-018-5559-z. Epub 2018 Jun 19.
• [12] O-GlcNAc transferase integrates metabolic pathways to regulate the stability of c-MYC in human prostate cancer cells.Cancer Res. 2013 Aug 15;73(16):5277-87. doi: 10.1158/0008-5472.CAN-13-0549. Epub 2013 May 29.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [17] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [18] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [23] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.