Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT14T7Q1)

DOT Name Hemopexin (HPX)
Synonyms Beta-1B-glycoprotein
Gene Name HPX
Related Disease
Advanced cancer ( )
Alcohol use disorder ( )
Neoplasm ( )
Subarachnoid hemorrhage ( )
Acroosteolysis dominant type ( )
Acute kidney injury ( )
Amelogenesis imperfecta ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Autoimmune disease ( )
Cerebral infarction ( )
Duchenne muscular dystrophy ( )
Hepatocellular carcinoma ( )
Liver cirrhosis ( )
Metabolic disorder ( )
Mood disorder ( )
Nephrotic syndrome ( )
Plasmodium falciparum malaria ( )
Pneumonia ( )
Pneumonitis ( )
Pulmonary tuberculosis ( )
Seminoma ( )
Sickle-cell anaemia ( )
Stroke ( )
Tuberculosis ( )
Type-1/2 diabetes ( )
High blood pressure ( )
Lupus nephritis ( )
Pulmonary emphysema ( )
Small lymphocytic lymphoma ( )
Arthritis ( )
Asthma ( )
Breast cancer ( )
Breast carcinoma ( )
Colorectal carcinoma ( )
Cystitis ( )
Nervous system inflammation ( )
Non-insulin dependent diabetes ( )
Periodontitis ( )
Thalassemia ( )
UniProt ID
HEMO_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
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Pfam ID
PF00045
Sequence
MARVLGAPVALGLWSLCWSLAIATPLPPTSAHGNVAEGETKPDPDVTERCSDGWSFDATT
LDDNGTMLFFKGEFVWKSHKWDRELISERWKNFPSPVDAAFRQGHNSVFLIKGDKVWVYP
PEKKEKGYPKLLQDEFPGIPSPLDAAVECHRGECQAEGVLFFQGDREWFWDLATGTMKER
SWPAVGNCSSALRWLGRYYCFQGNQFLRFDPVRGEVPPRYPRDVRDYFMPCPGRGHGHRN
GTGHGNSTHHGPEYMRCSPHLVLSALTSDNHGATYAFSGTHYWRLDTSRDGWHSWPIAHQ
WPQGPSAVDAAFSWEEKLYLVQGTQVYVFLTKGGYTLVSGYPKRLEKEVGTPHGIILDSV
DAAFICPGSSRLHIMAGRRLWWLDLKSGAQATWTELPWPHEKVDGALCMEKSLGPNSCSA
NGPGLYLIHGPNLYCYSDVEKLNAAKALPQPQNVTSLLGCTH
Function Binds heme and transports it to the liver for breakdown and iron recovery, after which the free hemopexin returns to the circulation.
Tissue Specificity Expressed by the liver and secreted in plasma.
Reactome Pathway
Scavenging of heme from plasma (R-HSA-2168880 )

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Definitive Biomarker [1]
Alcohol use disorder DISMB65Y Definitive Biomarker [2]
Neoplasm DISZKGEW Definitive Biomarker [3]
Subarachnoid hemorrhage DISI7I8Y Definitive Biomarker [4]
Acroosteolysis dominant type DISL732V Strong Genetic Variation [5]
Acute kidney injury DISXZG0T Strong Biomarker [6]
Amelogenesis imperfecta DISGYR9E Strong Genetic Variation [7]
Arteriosclerosis DISK5QGC Strong Biomarker [8]
Atherosclerosis DISMN9J3 Strong Biomarker [8]
Autoimmune disease DISORMTM Strong Biomarker [9]
Cerebral infarction DISR1WNP Strong Biomarker [10]
Duchenne muscular dystrophy DISRQ3NV Strong Biomarker [11]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [12]
Liver cirrhosis DIS4G1GX Strong Altered Expression [13]
Metabolic disorder DIS71G5H Strong Biomarker [14]
Mood disorder DISLVMWO Strong Altered Expression [15]
Nephrotic syndrome DISSPSC2 Strong Biomarker [16]
Plasmodium falciparum malaria DIS3Q9KF Strong Biomarker [17]
Pneumonia DIS8EF3M Strong Biomarker [18]
Pneumonitis DIS88E0K Strong Biomarker [18]
Pulmonary tuberculosis DIS6FLUM Strong Biomarker [19]
Seminoma DIS3J8LJ Strong Biomarker [20]
Sickle-cell anaemia DIS5YNZB Strong Biomarker [21]
Stroke DISX6UHX Strong Biomarker [22]
Tuberculosis DIS2YIMD Strong Biomarker [19]
Type-1/2 diabetes DISIUHAP Strong Biomarker [19]
High blood pressure DISY2OHH moderate Biomarker [23]
Lupus nephritis DISCVGPZ moderate Biomarker [24]
Pulmonary emphysema DIS5M7HZ moderate Biomarker [25]
Small lymphocytic lymphoma DIS30POX moderate Biomarker [26]
Arthritis DIST1YEL Disputed Biomarker [27]
Asthma DISW9QNS Limited Altered Expression [28]
Breast cancer DIS7DPX1 Limited Biomarker [29]
Breast carcinoma DIS2UE88 Limited Biomarker [29]
Colorectal carcinoma DIS5PYL0 Limited Biomarker [30]
Cystitis DIS2D4B9 Limited Biomarker [31]
Nervous system inflammation DISB3X5A Limited Biomarker [32]
Non-insulin dependent diabetes DISK1O5Z Limited Biomarker [33]
Periodontitis DISI9JOI Limited Biomarker [34]
Thalassemia DIS76XZB Limited Biomarker [35]
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⏷ Show the Full List of 40 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
16 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 Hemopexin (HPX). [36]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Hemopexin (HPX). [37]
Tretinoin DM49DUI Approved Tretinoin affects the expression of Hemopexin (HPX). [38]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Hemopexin (HPX). [39]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Hemopexin (HPX). [40]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Hemopexin (HPX). [41]
Triclosan DMZUR4N Approved Triclosan increases the expression of Hemopexin (HPX). [42]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Hemopexin (HPX). [43]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of Hemopexin (HPX). [44]
Amphotericin B DMTAJQE Approved Amphotericin B increases the expression of Hemopexin (HPX). [45]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Hemopexin (HPX). [47]
Belinostat DM6OC53 Phase 2 Belinostat decreases the expression of Hemopexin (HPX). [47]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Hemopexin (HPX). [48]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Hemopexin (HPX). [49]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Hemopexin (HPX). [50]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde decreases the expression of Hemopexin (HPX). [51]
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⏷ Show the Full List of 16 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Olanzapine DMPFN6Y Approved Olanzapine affects the phosphorylation of Hemopexin (HPX). [46]
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References

1 Targeting the Hemopexin-like Domain of Latent Matrix Metalloproteinase-9 (proMMP-9) with a Small Molecule Inhibitor Prevents the Formation of Focal Adhesion Junctions.ACS Chem Biol. 2017 Nov 17;12(11):2788-2803. doi: 10.1021/acschembio.7b00758. Epub 2017 Oct 10.
2 Proteomic Profiling of Exosomes Derived from Plasma of HIV-Infected Alcohol Drinkers and Cigarette Smokers.J Neuroimmune Pharmacol. 2020 Sep;15(3):501-519. doi: 10.1007/s11481-019-09853-2. Epub 2019 May 8.
3 Novel MT1-MMP small-molecule inhibitors based on insights into hemopexin domain function in tumor growth.Cancer Res. 2012 May 1;72(9):2339-49. doi: 10.1158/0008-5472.CAN-11-4149. Epub 2012 Mar 9.
4 The role of haptoglobin and hemopexin in the prevention of delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage: a review of current literature.Neurosurg Rev. 2020 Oct;43(5):1273-1288. doi: 10.1007/s10143-019-01169-2. Epub 2019 Sep 6.
5 A novel matrix metalloproteinase 2 (MMP2) terminal hemopexin domain mutation in a family with multicentric osteolysis with nodulosis and arthritis with cardiac defects.Eur J Hum Genet. 2009 May;17(5):565-72. doi: 10.1038/ejhg.2008.204. Epub 2008 Nov 5.
6 A Multiplatform Approach for the Discovery of Novel Drug-Induced Kidney Injury Biomarkers.Chem Res Toxicol. 2017 Oct 16;30(10):1823-1834. doi: 10.1021/acs.chemrestox.7b00159. Epub 2017 Sep 27.
7 MMP20 hemopexin domain mutation in amelogenesis imperfecta.J Dent Res. 2010 Jan;89(1):46-50. doi: 10.1177/0022034509352844.
8 Apolipoprotein E-/- Mice Lacking Hemopexin Develop Increased Atherosclerosis via Mechanisms That Include Oxidative Stress and Altered Macrophage Function.Arterioscler Thromb Vasc Biol. 2016 Jun;36(6):1152-63. doi: 10.1161/ATVBAHA.115.306991. Epub 2016 Apr 14.
9 Lack of plasma protein hemopexin dampens mercury-induced autoimmune response in mice.J Immunol. 2008 Aug 1;181(3):1937-47. doi: 10.4049/jimmunol.181.3.1937.
10 Hemopexin promotes angiogenesis via up-regulating HO-1 in rats after cerebral ischemia-reperfusion injury.BMC Anesthesiol. 2018 Jan 3;18(1):2. doi: 10.1186/s12871-017-0466-4.
11 Serum myoglobin in Duchenne muscular dystrophy carrier detection: a comparison with creatine kinase and hemopexin using logistic discrimination.Am J Med Genet. 1984 Jun;18(2):279-87. doi: 10.1002/ajmg.1320180212.
12 Heme-hemopexin-mediated induction of metallothionein gene expression.J Biol Chem. 1992 Aug 15;267(23):16379-84.
13 Quantitative analysis of core fucosylation of serum proteins in liver diseases by LC-MS-MRM.J Proteomics. 2018 Oct 30;189:67-74. doi: 10.1016/j.jprot.2018.02.003. Epub 2018 Feb 7.
14 Physiologic and genetic evidence links hemopexin to triglycerides in mice and humans.Int J Obes (Lond). 2017 Apr;41(4):631-638. doi: 10.1038/ijo.2017.19. Epub 2017 Jan 25.
15 The Compensatory Immune-Regulatory Reflex System (CIRS) in Depression and Bipolar Disorder.Mol Neurobiol. 2018 Dec;55(12):8885-8903. doi: 10.1007/s12035-018-1016-x. Epub 2018 Apr 2.
16 Production of hemopexin by TNF-alpha stimulated human mesangial cells.Kidney Int. 2003 May;63(5):1681-6. doi: 10.1046/j.1523-1755.2003.00907.x.
17 Prolonged neutrophil dysfunction after Plasmodium falciparum malaria is related to hemolysis and heme oxygenase-1 induction.J Immunol. 2012 Dec 1;189(11):5336-46. doi: 10.4049/jimmunol.1201028. Epub 2012 Oct 24.
18 Protective effect of hemopexin on systemic inflammation and acute lung injury in an endotoxemia model.J Surg Res. 2017 May 15;212:15-21. doi: 10.1016/j.jss.2016.12.020. Epub 2016 Dec 28.
19 Modulation of iron status biomarkers in tuberculosis-diabetes co-morbidity.Tuberculosis (Edinb). 2018 Jan;108:127-135. doi: 10.1016/j.tube.2017.11.011. Epub 2017 Nov 24.
20 Genome-wide expression profiling reveals new insights into pathogenesis and progression of testicular germ cell tumors.Cancer Genomics Proteomics. 2007 Sep-Oct;4(5):359-67.
21 Differences in heme and hemopexin content in lipoproteins from patients with sickle cell disease.J Clin Lipidol. 2018 Nov-Dec;12(6):1532-1538. doi: 10.1016/j.jacl.2018.08.002. Epub 2018 Aug 14.
22 Hemopexin alleviates cognitive dysfunction after focal cerebral ischemia-reperfusion injury in rats.BMC Anesthesiol. 2019 Jan 15;19(1):13. doi: 10.1186/s12871-019-0681-2.
23 Endothelial dysfunction inhibits the ability of haptoglobin to prevent hemoglobin-induced hypertension.Am J Physiol Heart Circ Physiol. 2017 Jun 1;312(6):H1120-H1127. doi: 10.1152/ajpheart.00851.2016. Epub 2017 Mar 17.
24 Prospective validation of a novel renal activity index of lupus nephritis.Lupus. 2017 Aug;26(9):927-936. doi: 10.1177/0961203316684212. Epub 2016 Dec 19.
25 Heme scavenging reduces pulmonary endoplasmic reticulum stress, fibrosis, and emphysema.JCI Insight. 2018 Nov 2;3(21):e120694. doi: 10.1172/jci.insight.120694.
26 Matrix metalloproteinase-9 promotes chronic lymphocytic leukemia b cell survival through its hemopexin domain.Cancer Cell. 2010 Feb 17;17(2):160-72. doi: 10.1016/j.ccr.2009.12.044.
27 Mass spectrometry-based analysis of cerebrospinal fluid from arthritis patients-immune-related candidate proteins affected by TNF blocking treatment.Arthritis Res Ther. 2019 Feb 15;21(1):60. doi: 10.1186/s13075-019-1846-6.
28 Relationship between group-specific component protein and the development of asthma.Am J Respir Crit Care Med. 2011 Sep 1;184(5):528-36. doi: 10.1164/rccm.201006-0951OC.
29 Identification of ApoA1, HPX and POTEE genes by omic analysis in breast cancer.Oncol Rep. 2014 Sep;32(3):1078-86. doi: 10.3892/or.2014.3277. Epub 2014 Jun 23.
30 MMP-9-hemopexin domain hampers adhesion and migration of colorectal cancer cells.Int J Oncol. 2007 Apr;30(4):985-92. doi: 10.3892/ijo.30.4.985.
31 Intravesical administration of blebbistatin prevents cyclophosphamide-induced toxicity of the urinary bladder in female Wistar rats.Neurourol Urodyn. 2019 Apr;38(4):1044-1052. doi: 10.1002/nau.23973. Epub 2019 Mar 14.
32 Acute-phase protein hemopexin is a negative regulator of Th17 response and experimental autoimmune encephalomyelitis development.J Immunol. 2013 Dec 1;191(11):5451-9. doi: 10.4049/jimmunol.1203076. Epub 2013 Oct 23.
33 Impact of diabetes mellitus on the relationships between iron-, inflammatory- and oxidative stress status.Diabetes Metab Res Rev. 2006 Nov-Dec;22(6):444-54. doi: 10.1002/dmrr.635.
34 Assessing a multiplex-targeted proteomics approach for the clinical diagnosis of periodontitis using saliva samples.Bioanalysis. 2018 Jan;10(1):35-45. doi: 10.4155/bio-2017-0218. Epub 2017 Dec 15.
35 Quantitative proteomics of plasma vesicles identify novel biomarkers for hemoglobin E/-thalassemic patients.Blood Adv. 2018 Jan 23;2(2):95-104. doi: 10.1182/bloodadvances.2017011726.
36 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.
37 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.
38 Molecular characterization of a toxicological tipping point during human stem cell differentiation. Reprod Toxicol. 2020 Jan;91:1-13. doi: 10.1016/j.reprotox.2019.10.001. Epub 2019 Oct 7.
39 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
40 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
41 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
42 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
43 Proteomic analysis of hepatic effects of phenobarbital in mice with humanized liver. Arch Toxicol. 2022 Oct;96(10):2739-2754. doi: 10.1007/s00204-022-03338-7. Epub 2022 Jul 26.
44 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.
45 Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
46 Effects of olanzapine on serum protein phosphorylation patterns in patients with schizophrenia. Proteomics Clin Appl. 2015 Oct;9(9-10):907-16. doi: 10.1002/prca.201400148. Epub 2015 May 15.
47 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.
48 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
49 Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
50 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.
51 Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.