Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHXU264)

DOT Name	Azurocidin (AZU1)
Synonyms	Cationic antimicrobial protein CAP37; Heparin-binding protein; HBP; hHBP
Gene Name	AZU1
Related Disease	Non-insulin dependent diabetes ( ) Abscess ( ) Advanced cancer ( ) Alzheimer disease ( ) Arteriosclerosis ( ) Atherosclerosis ( ) Bacterial meningitis ( ) Breast cancer ( ) Breast carcinoma ( ) Breast neoplasm ( ) Chronic obstructive pulmonary disease ( ) Congestive heart failure ( ) Cystic fibrosis ( ) Diabetic kidney disease ( ) Fatty liver disease ( ) IgA nephropathy ( ) Intrahepatic cholangiocarcinoma ( ) Liver cirrhosis ( ) Myocardial infarction ( ) Neoplasm ( ) Pancreas disorder ( ) Respiratory syncytial virus infection ( ) Urinary tract infection ( ) Bacterial infection ( ) Clear cell renal carcinoma ( ) Hepatocellular carcinoma ( ) Prostate cancer ( ) Periodontal disease ( ) Periodontitis ( )
UniProt ID	CAP7_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1A7S; 1AE5; 1FY1; 1FY3
Pfam ID	PF00089
Sequence	MTRLTVLALLAGLLASSRAGSSPLLDIVGGRKARPRQFPFLASIQNQGRHFCGGALIHAR FVMTAASCFQSQNPGVSTVVLGAYDLRRRERQSRQTFSISSMSENGYDPQQNLNDLMLLQ LDREANLTSSVTILPLPLQNATVEAGTRCQVAGWGSQRSGGRLSRFPRFVNVTVTPEDQC RPNNVCTGVLTRRGGICNGDGGTPLVCEGLAHGVASFSLGPCGRGPDFFTRVALFRDWID GVLNNPGPGPA
Function	This is a neutrophil granule-derived antibacterial and monocyte- and fibroblast-specific chemotactic glycoprotein. Binds heparin. The cytotoxic action is limited to many species of Gram-negative bacteria; this specificity may be explained by a strong affinity of the very basic N-terminal half for the negatively charged lipopolysaccharides that are unique to the Gram-negative bacterial outer envelope. It may play a role in mediating recruitment of monocytes in the second wave of inflammation. Has antibacterial activity against the Gram-negative bacterium P.aeruginosa, this activity is inhibited by LPS from P.aeruginosa. Acting alone, it does not have antimicrobial activity against the Gram-negative bacteria A.actinomycetemcomitans ATCC 29532, A.actinomycetemcomitans NCTC 9709, A.actinomycetemcomitans FDC-Y4, H.aphrophilus ATCC 13252, E.corrodens ATCC 23834, C.sputigena ATCC 33123, Capnocytophaga sp ATCC 33124, Capnocytophaga sp ATCC 27872 or E.coli ML-35. Has antibacterial activity against C.sputigena ATCC 33123 when acting synergistically with either elastase or cathepsin G.
KEGG Pathway	Neutrophil extracellular trap formation (hsa04613 )
Reactome Pathway	Neutrophil degranulation (R-HSA-6798695 )

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[1]
Abscess	DISAP982	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[4]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[5]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[5]
Bacterial meningitis	DISRP9SL	Strong	Genetic Variation	[6]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[9]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Biomarker	[10]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[10]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[11]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[12]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[13]
IgA nephropathy	DISZ8MTK	Strong	Genetic Variation	[14]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Biomarker	[15]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[16]
Myocardial infarction	DIS655KI	Strong	Biomarker	[17]
Neoplasm	DISZKGEW	Strong	Biomarker	[18]
Pancreas disorder	DISDH7NI	Strong	Biomarker	[19]
Respiratory syncytial virus infection	DIS7FWHY	Strong	Altered Expression	[20]
Urinary tract infection	DISMT6UV	Strong	Biomarker	[21]
Bacterial infection	DIS5QJ9S	moderate	Biomarker	[22]
Clear cell renal carcinoma	DISBXRFJ	moderate	Biomarker	[23]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[24]
Prostate cancer	DISF190Y	moderate	Altered Expression	[25]
Periodontal disease	DISJQHVN	Limited	Biomarker	[26]
Periodontitis	DISI9JOI	Limited	Altered Expression	[26]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Azurocidin (AZU1).	[27]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Azurocidin (AZU1).	[33]
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8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Azurocidin (AZU1).	[28]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Azurocidin (AZU1).	[29]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Azurocidin (AZU1).	[30]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Azurocidin (AZU1).	[31]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Azurocidin (AZU1).	[32]
PF-3758309	DM36PKZ	Phase 1	PF-3758309 decreases the expression of Azurocidin (AZU1).	[34]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Azurocidin (AZU1).	[35]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl decreases the expression of Azurocidin (AZU1).	[35]
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⏷ Show the Full List of 8 Drug(s)

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	iTRAQ-based quantitative proteomic analysis provides insight for molecular mechanism of neuroticism.Clin Proteomics. 2019 Nov 8;16:38. doi: 10.1186/s12014-019-9259-8. eCollection 2019.
4	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.
5	Functional modulation of smooth muscle cells by the inflammatory mediator CAP37.Microvasc Res. 2004 Mar;67(2):168-81. doi: 10.1016/j.mvr.2003.12.007.
6	Meningococcal Antigen Typing System (MATS)-Based Neisseria meningitidis Serogroup B Coverage Prediction for the MenB-4C Vaccine in the United States.mSphere. 2017 Nov 15;2(6):e00261-17. doi: 10.1128/mSphere.00261-17. eCollection 2017 Nov-Dec.
7	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.
8	High-level expression, purification and pro-apoptosis activity of HIV-TAT-survivin (T34A) mutant to cancer cells in vitro.J Biotechnol. 2006 May 29;123(3):367-78. doi: 10.1016/j.jbiotec.2005.11.018. Epub 2006 Jan 10.
9	AZU-1: a candidate breast tumor suppressor and biomarker for tumor progression.Mol Biol Cell. 2000 Apr;11(4):1357-67. doi: 10.1091/mbc.11.4.1357.
10	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.
11	Heparin-binding protein in sputum as a marker of pulmonary inflammation, lung function, and bacterial load in children with cystic fibrosis.BMC Pulm Med. 2018 Jun 20;18(1):104. doi: 10.1186/s12890-018-0668-7.
12	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.
13	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.
14	Characterization of glomerular extracellular matrix in IgA nephropathy by proteomic analysis of laser-captured microdissected glomeruli.BMC Nephrol. 2019 Nov 14;20(1):410. doi: 10.1186/s12882-019-1598-1.
15	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.
16	Significance of Heparin-Binding Protein and D-dimers in the Early Diagnosis of Spontaneous Bacterial Peritonitis.Mediators Inflamm. 2018 Sep 30;2018:1969108. doi: 10.1155/2018/1969108. eCollection 2018.
17	A Novel Marker of Inflammation: Azurocidin in Patients with ST Segment Elevation Myocardial Infarction.Int J Mol Sci. 2018 Nov 29;19(12):3797. doi: 10.3390/ijms19123797.
18	Changes in the microarchitecture of the pancreatic cancer stroma are linked to neutrophil-dependent reprogramming of stellate cells and reflected by diffusion-weighted magnetic resonance imaging.Theranostics. 2018 Jan 1;8(1):13-30. doi: 10.7150/thno.21089. eCollection 2018.
19	The heparin-binding protein interactome in pancreatic diseases.Pancreatology. 2013 Nov-Dec;13(6):598-604. doi: 10.1016/j.pan.2013.08.004. Epub 2013 Aug 26.
20	Airway response to respiratory syncytial virus has incidental antibacterial effects.Nat Commun. 2019 May 17;10(1):2218. doi: 10.1038/s41467-019-10222-z.
21	New markers of urinary tract infection.Clin Chim Acta. 2017 Aug;471:286-291. doi: 10.1016/j.cca.2017.06.003. Epub 2017 Jun 13.
22	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.
23	Extracellular vesicles isolated from human renal cell carcinoma tissues disrupt vascular endothelial cell morphology via azurocidin.Int J Cancer. 2018 Feb 1;142(3):607-617. doi: 10.1002/ijc.31080. Epub 2017 Oct 14.
24	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.
25	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.
26	Azurocidin in gingival crevicular fluid as a potential biomarker of chronic periodontitis.J Periodontal Res. 2020 Apr;55(2):209-214. doi: 10.1111/jre.12703. Epub 2019 Oct 14.
27	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.
28	Arsenic trioxide augments all-trans retinoic acid-induced differentiation of HL-60 cells. Life Sci. 2016 Mar 15;149:42-50. doi: 10.1016/j.lfs.2016.02.054. Epub 2016 Feb 16.
29	Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
30	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.
31	Molecular mechanism of action of bisphenol and bisphenol A mediated by oestrogen receptor alpha in growth and apoptosis of breast cancer cells. Br J Pharmacol. 2013 May;169(1):167-78.
32	Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
33	Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
34	Inhibition of neuroblastoma proliferation by PF-3758309, a small-molecule inhibitor that targets p21-activated kinase 4. Oncol Rep. 2017 Nov;38(5):2705-2716. doi: 10.3892/or.2017.5989. Epub 2017 Sep 22.
35	Inhibition of CXCL12-mediated chemotaxis of Jurkat cells by direct immunotoxicants. Arch Toxicol. 2016 Jul;90(7):1685-94. doi: 10.1007/s00204-015-1585-7. Epub 2015 Aug 28.