Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8BWXTV)

DOT Name	Lipocalin-1 (LCN1)
Synonyms	Tear lipocalin; Tlc; Tear prealbumin; TP; von Ebner gland protein; VEG protein
Gene Name	LCN1
Related Disease	Type-1/2 diabetes ( ) Bladder cancer ( ) Breast cancer ( ) Breast carcinoma ( ) Bronchiectasis ( ) Bronchiolitis obliterans syndrome ( ) Clear cell renal carcinoma ( ) Cystic fibrosis ( ) Diabetic kidney disease ( ) Diabetic retinopathy ( ) Essential hypertension ( ) Gastroesophageal reflux disease ( ) High blood pressure ( ) Multiple sclerosis ( ) Neoplasm ( ) Non-insulin dependent diabetes ( ) Oropharyngeal squamous cell carcinoma ( ) Parkinson disease ( ) Renal cell carcinoma ( ) Schizophrenia ( ) Sjogren syndrome ( ) Tarsal-carpal coalition syndrome ( ) Urinary bladder cancer ( ) Urinary bladder neoplasm ( ) Vibrio cholerae infection ( ) Advanced cancer ( ) Adult glioblastoma ( ) Glioblastoma multiforme ( ) Psychotic disorder ( ) Pulmonary emphysema ( ) Tuberculosis ( )
UniProt ID	LCN1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1XKI; 3EYC; 4QAF; 5T43
Pfam ID	PF00061
Sequence	MKPLLLAVSLGLIAALQAHHLLASDEEIQDVSGTWYLKAMTVDREFPEMNLESVTPMTLT TLEGGNLEAKVTMLISGRCQEVKAVLEKTDEPGKYTADGGKHVAYIIRSHVKDHYIFYCE GELHGKPVRGVKLVGRDPKNNLEALEDFEKAAGARGLSTESILIPRQSETCSPGSD
Function	Could play a role in taste reception. Could be necessary for the concentration and delivery of sapid molecules in the gustatory system. Can bind various ligands, with chemical structures ranging from lipids and retinoids to the macrocyclic antibiotic rifampicin and even to microbial siderophores. Exhibits an extremely wide ligand pocket.
Tissue Specificity	Mainly expressed in lachrymal and salivary glands. Also expressed in the prostate.
Reactome Pathway	Transport of fatty acids (R-HSA-804914 )

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Type-1/2 diabetes	DISIUHAP	Definitive	Biomarker	[1]
Bladder cancer	DISUHNM0	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Bronchiectasis	DIS5MYEE	Strong	Biomarker	[4]
Bronchiolitis obliterans syndrome	DISCK9IV	Strong	Genetic Variation	[5]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[6]
Cystic fibrosis	DIS2OK1Q	Strong	Altered Expression	[7]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[8]
Diabetic retinopathy	DISHGUJM	Strong	Biomarker	[9]
Essential hypertension	DIS7WI98	Strong	Altered Expression	[10]
Gastroesophageal reflux disease	DISQ8G5S	Strong	Biomarker	[11]
High blood pressure	DISY2OHH	Strong	Altered Expression	[10]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[12]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[8]
Oropharyngeal squamous cell carcinoma	DIS7D7QV	Strong	Biomarker	[13]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[14]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[6]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[15]
Sjogren syndrome	DISUBX7H	Strong	Biomarker	[16]
Tarsal-carpal coalition syndrome	DISY90L2	Strong	Biomarker	[17]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[2]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[2]
Vibrio cholerae infection	DISW7E3U	Strong	Altered Expression	[18]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[3]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[19]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[19]
Psychotic disorder	DIS4UQOT	Limited	Genetic Variation	[20]
Pulmonary emphysema	DIS5M7HZ	Limited	Biomarker	[21]
Tuberculosis	DIS2YIMD	Limited	Biomarker	[22]
------------------------------------------------------------------------------------


⏷ Show the Full List of 31 Disease(s)

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 Lipocalin-1 (LCN1).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Lipocalin-1 (LCN1).	[29]
------------------------------------------------------------------------------------

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin affects the binding of Lipocalin-1 (LCN1).	[24]
1-anilinonaphthalene-8-sulfonic acid	DMNGY0E	Investigative	1-anilinonaphthalene-8-sulfonic acid affects the binding of Lipocalin-1 (LCN1).	[24]
------------------------------------------------------------------------------------

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Lipocalin-1 (LCN1).	[25]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Lipocalin-1 (LCN1).	[26]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Lipocalin-1 (LCN1).	[27]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Lipocalin-1 (LCN1).	[28]
------------------------------------------------------------------------------------

References

1	Impact of diabetes mellitus on functional exercise capacity and pulmonary functions in patients with diabetes and healthy persons.BMC Endocr Disord. 2019 Jan 3;19(1):2. doi: 10.1186/s12902-018-0328-1.
2	A Potent Chemotherapeutic Strategy with Eg5 Inhibitor against Gemcitabine Resistant Bladder Cancer.PLoS One. 2015 Dec 10;10(12):e0144484. doi: 10.1371/journal.pone.0144484. eCollection 2015.
3	Identification of LCN1 as a Potential Biomarker for Breast Cancer by Bioinformatic Analysis.DNA Cell Biol. 2019 Oct;38(10):1088-1099. doi: 10.1089/dna.2019.4843. Epub 2019 Aug 19.
4	Residual volume/total lung capacity ratio confers limited additive significance to lung clearance index for assessment of adults with bronchiectasis.PLoS One. 2017 Sep 8;12(9):e0183779. doi: 10.1371/journal.pone.0183779. eCollection 2017.
5	Airway inflammation in children and adolescents with bronchiolitis obliterans.Cytokine. 2015 May;73(1):156-62. doi: 10.1016/j.cyto.2014.10.026. Epub 2015 Mar 6.
6	Four new human renal cell carcinoma cell lines expressing globo-series gangliosides.Tohoku J Exp Med. 1999 Oct;189(2):95-105. doi: 10.1620/tjem.189.95.
7	Identification of a lipocalin in mucosal glands of the human tracheobronchial tree and its enhanced secretion in cystic fibrosis.Lab Invest. 1998 Sep;78(9):1121-9.
8	Urinary Neutrophil Gelatinase-Associated Lipocalin Is Complementary to Albuminuria in Diagnosis of Early-Stage Diabetic Kidney Disease in Type 2 Diabetes.Biomed Res Int. 2017;2017:4691389. doi: 10.1155/2017/4691389. Epub 2017 Aug 6.
9	Sensitive tear screening of diabetic retinopathy with dual biomarkers enabled using a rapid electrokinetic patterning platform.Lab Chip. 2020 Jan 21;20(2):356-362. doi: 10.1039/c9lc00975b. Epub 2019 Dec 18.
10	Global DNA methylation changes in blood of patients with essential hypertension.Med Sci Monit. 2010 Mar;16(3):CR149-155.
11	Sputum proteomic signature of gastro-oesophageal reflux in patients with severe asthma.Respir Med. 2019 Apr;150:66-73. doi: 10.1016/j.rmed.2019.02.008. Epub 2019 Feb 11.
12	Multiple sclerosis: Presence of serum antibodies to lipids and predominance of cholesterol recognition.J Neurosci Res. 2017 Oct;95(10):1984-1992. doi: 10.1002/jnr.24062. Epub 2017 May 8.
13	Elemental Zn and its Binding Protein Zinc-2-Glycoprotein are Elevated in HPV-Positive Oropharyngeal Squamous Cell Carcinoma.Sci Rep. 2019 Nov 18;9(1):16965. doi: 10.1038/s41598-019-53268-1.
14	Bioassay-guided Isolation of Neuroprotective Fatty Acids from Nigella sativa against 1-methyl-4-phenylpyridinium-induced Neurotoxicity.Pharmacogn Mag. 2017 Oct-Dec;13(52):627-633. doi: 10.4103/pm.pm_470_16. Epub 2017 Nov 13.
15	Thought, language, and communication deficits and association with everyday functional outcomes among community-dwelling middle-aged and older adults with schizophrenia.Schizophr Res. 2018 Jun;196:29-34. doi: 10.1016/j.schres.2017.07.017. Epub 2017 Aug 1.
16	Identification of tear lipocalin as a novel autoantigen target in Sjgren's syndrome.J Autoimmun. 2005 Nov;25(3):229-34. doi: 10.1016/j.jaut.2005.09.021. Epub 2005 Oct 24.
17	DNA damage in human transitional cell carcinoma cells after exposure to the proximate metabolite of the bladder carcinogen 4-aminobiphenyl.Environ Mol Mutagen. 2001;38(1):1-11. doi: 10.1002/em.1044.
18	Conversion of a recA-Mediated Non-toxigenic Vibrio cholerae O1 Strain to a Toxigenic Strain Using Chitin-Induced Transformation.Front Microbiol. 2019 Nov 7;10:2562. doi: 10.3389/fmicb.2019.02562. eCollection 2019.
19	Methylated of genes behaving as potential biomarkers in evaluating malignant degree of glioblastoma.J Cell Physiol. 2017 Dec;232(12):3622-3630. doi: 10.1002/jcp.25831. Epub 2017 Mar 27.
20	The role of social isolation and social cognition in thought disorder.Psychiatry Res. 2018 Nov;269:56-63. doi: 10.1016/j.psychres.2018.08.048. Epub 2018 Aug 16.
21	Combined pulmonary fibrosis and emphysema: How does cohabitation affect respiratory functions?.Adv Med Sci. 2019 Sep;64(2):285-291. doi: 10.1016/j.advms.2019.03.005. Epub 2019 Apr 1.
22	Studies of polymorphic DNA fingerprinting and lipid pattern of Mycobacterium tuberculosis patient isolates in Japan.Microbiol Immunol. 1997;41(2):107-19. doi: 10.1111/j.1348-0421.1997.tb01176.x.
23	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.
24	Comparative ligand-binding analysis of ten human lipocalins. Biochim Biophys Acta. 2006 Feb;1764(2):161-73. doi: 10.1016/j.bbapap.2005.12.006. Epub 2006 Jan 6.
25	Endoplasmic reticulum stress contributes to arsenic trioxide-induced intrinsic apoptosis in human umbilical and bone marrow mesenchymal stem cells. Environ Toxicol. 2016 Mar;31(3):314-28.
26	Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
27	Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
28	Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
29	DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.