Details of Drug Off-Target (DOT)

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

DOT Name	Alpha-1-acid glycoprotein 1 (ORM1)
Synonyms	AGP 1; Orosomucoid-1; OMD 1
Gene Name	ORM1
Related Disease	Cognitive impairment ( ) Acute kidney injury ( ) Adenocarcinoma ( ) Advanced cancer ( ) Allergic asthma ( ) Allergic contact dermatitis ( ) Alzheimer disease ( ) Atopic dermatitis ( ) Carcinoma ( ) Cardiac failure ( ) Congestive heart failure ( ) Depression ( ) Familial adenomatous polyposis ( ) Hepatitis B virus infection ( ) Hepatocellular carcinoma ( ) Lung adenocarcinoma ( ) Lung cancer ( ) Lung carcinoma ( ) Mood disorder ( ) Non-small-cell lung cancer ( ) Obesity ( ) Psoriasis ( ) Sarcoidosis ( ) Squamous cell carcinoma ( ) Liver failure ( ) Pulmonary tuberculosis ( ) Asthma ( ) Carcinoma of liver and intrahepatic biliary tract ( ) Liver cancer ( ) Pancreatic cancer ( ) Pancreatic ductal carcinoma ( ) Type-1 diabetes ( )
UniProt ID	A1AG1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	3KQ0
Pfam ID	PF00061
Sequence	MALSWVLTVLSLLPLLEAQIPLCANLVPVPITNATLDRITGKWFYIASAFRNEEYNKSVQ EIQATFFYFTPNKTEDTIFLREYQTRQDQCIYNTTYLNVQRENGTISRYVGGQEHFAHLL ILRDTKTYMLAFDVNDEKNWGLSVYADKPETTKEQLGEFYEALDCLRIPKSDVVYTDWKK DKCEPLEKQHEKERKQEEGES
Function	Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction.
Tissue Specificity	Expressed by the liver and secreted in plasma.
Reactome Pathway	Neutrophil degranulation (R-HSA-6798695 ) Platelet degranulation (R-HSA-114608 )

Molecular Interaction Atlas (MIA) of This DOT

32 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Cognitive impairment	DISH2ERD	Definitive	Biomarker	[1]
Acute kidney injury	DISXZG0T	Strong	Biomarker	[2]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[4]
Allergic asthma	DISHF0H3	Strong	Genetic Variation	[5]
Allergic contact dermatitis	DISFFVF9	Strong	Genetic Variation	[6]
Alzheimer disease	DISF8S70	Strong	Biomarker	[7]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[8]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[4]
Cardiac failure	DISDC067	Strong	Biomarker	[9]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[9]
Depression	DIS3XJ69	Strong	Biomarker	[10]
Familial adenomatous polyposis	DISW53RE	Strong	Altered Expression	[11]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[12]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[13]
Lung cancer	DISCM4YA	Strong	Biomarker	[3]
Lung carcinoma	DISTR26C	Strong	Biomarker	[3]
Mood disorder	DISLVMWO	Strong	Genetic Variation	[14]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[15]
Obesity	DIS47Y1K	Strong	Altered Expression	[16]
Psoriasis	DIS59VMN	Strong	Biomarker	[17]
Sarcoidosis	DISE5B8Z	Strong	Genetic Variation	[6]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[3]
Liver failure	DISLGEL6	moderate	Therapeutic	[18]
Pulmonary tuberculosis	DIS6FLUM	moderate	Biomarker	[19]
Asthma	DISW9QNS	Limited	Genetic Variation	[20]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Altered Expression	[21]
Liver cancer	DISDE4BI	Limited	Altered Expression	[21]
Pancreatic cancer	DISJC981	Limited	Biomarker	[22]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Altered Expression	[22]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[23]
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⏷ Show the Full List of 32 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Warfarin	DMJYCVW	Approved	Alpha-1-acid glycoprotein 1 (ORM1) increases the response to substance of Warfarin.	[41]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Alpha-1-acid glycoprotein 1 (ORM1).	[24]
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16 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Alpha-1-acid glycoprotein 1 (ORM1).	[25]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Alpha-1-acid glycoprotein 1 (ORM1).	[26]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Alpha-1-acid glycoprotein 1 (ORM1).	[27]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Alpha-1-acid glycoprotein 1 (ORM1).	[28]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Alpha-1-acid glycoprotein 1 (ORM1).	[25]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Alpha-1-acid glycoprotein 1 (ORM1).	[29]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Alpha-1-acid glycoprotein 1 (ORM1).	[29]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Alpha-1-acid glycoprotein 1 (ORM1).	[30]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Alpha-1-acid glycoprotein 1 (ORM1).	[31]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Alpha-1-acid glycoprotein 1 (ORM1).	[33]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Alpha-1-acid glycoprotein 1 (ORM1).	[34]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Alpha-1-acid glycoprotein 1 (ORM1).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Alpha-1-acid glycoprotein 1 (ORM1).	[36]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Alpha-1-acid glycoprotein 1 (ORM1).	[37]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Alpha-1-acid glycoprotein 1 (ORM1).	[38]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Alpha-1-acid glycoprotein 1 (ORM1).	[39]
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⏷ Show the Full List of 16 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Lidocaine	DML4ZOT	Approved	Lidocaine affects the binding of Alpha-1-acid glycoprotein 1 (ORM1).	[32]
Dipyridamole	DMXY30O	Approved	Dipyridamole affects the binding of Alpha-1-acid glycoprotein 1 (ORM1).	[32]
Chlorpromazine	DMBGZI3	Phase 3 Trial	Chlorpromazine affects the binding of Alpha-1-acid glycoprotein 1 (ORM1).	[32]
1-anilinonaphthalene-8-sulfonic acid	DMNGY0E	Investigative	1-anilinonaphthalene-8-sulfonic acid affects the binding of Alpha-1-acid glycoprotein 1 (ORM1).	[40]
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References

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2	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.
3	Glycosylated Alpha-1-acid glycoprotein 1 as a potential lung cancer serum biomarker.Int J Biochem Cell Biol. 2016 Jan;70:68-75. doi: 10.1016/j.biocel.2015.11.006. Epub 2015 Nov 10.
4	Association between orosomucoid types and cancer.Oncology. 1995 Nov-Dec;52(6):498-500. doi: 10.1159/000227518.
5	Investigating the Association of Orosomucoid 1-like 3 (ORMDL3) Gene Polymorphism (rs12603332) with Susceptibility to Allergic Asthma in Iranian Northwestern Azeri Population.Iran J Allergy Asthma Immunol. 2018 Dec 1;17(6):526-532.
6	Orosomucoid types in allergic contact dermatitis.Hum Hered. 1995 Mar-Apr;45(2):117-20. doi: 10.1159/000154269.
7	A simplified and sensitive method to identify Alzheimer's disease biomarker candidates using patient-derived induced pluripotent stem cells (iPSCs).J Biochem. 2017 Dec 1;162(6):391-394. doi: 10.1093/jb/mvx058.
8	Vaccinia virus-specific molecular signature in atopic dermatitis skin.J Allergy Clin Immunol. 2010 Jan;125(1):153-159.e28. doi: 10.1016/j.jaci.2009.10.024.
9	Paradoxical Effects of Sodium-Calcium Exchanger Inhibition on Torsade de Pointes and Early Afterdepolarization in a Heart Failure Rabbit Model.J Cardiovasc Pharmacol. 2018 Aug;72(2):97-105. doi: 10.1097/FJC.0000000000000598.
10	Evidence for possible linkage between genetic markers and affective disorders.Biol Psychiatry. 1988 Dec;24(8):903-17. doi: 10.1016/0006-3223(88)90225-9.
11	A proteomics approach to identify changes in protein profiles in serum of Familial Adenomatous Polyposis patients.Cancer Lett. 2008 Dec 8;272(1):40-52. doi: 10.1016/j.canlet.2008.06.021. Epub 2008 Jul 29.
12	Urine -fetoprotein and orosomucoid 1 as biomarkers of hepatitis B virus-associated hepatocellular carcinoma.Am J Physiol Gastrointest Liver Physiol. 2020 Feb 1;318(2):G305-G312. doi: 10.1152/ajpgi.00267.2019. Epub 2019 Nov 18.
13	Serum -1 Acid Glycoprotein is a Biomarker for the Prediction of Targeted Therapy Resistance in Advanced EGFR-positive Lung Adenocarcinoma.Comb Chem High Throughput Screen. 2018;21(10):755-759. doi: 10.2174/1386207322666190119163024.
14	A linkage study of affective disorder with DNA markers for the ABO-AK1-ORM linkage group near the dopamine beta hydroxylase gene.Biol Psychiatry. 1994 Oct 1;36(7):434-42. doi: 10.1016/0006-3223(94)90638-6.
15	Dramatically changed immune-related molecules as early diagnostic biomarkers of non-small cell lung cancer.FEBS J. 2020 Feb;287(4):783-799. doi: 10.1111/febs.15051. Epub 2019 Sep 20.
16	Orosomucoid expression profiles in liver, adipose tissues and serum of lean and obese domestic pigs, Gttingen minipigs and Ossabaw minipigs.Vet Immunol Immunopathol. 2013 Feb 15;151(3-4):325-30. doi: 10.1016/j.vetimm.2012.11.002. Epub 2012 Nov 27.
17	Urinary orosomucoid: a new marker of cardiovascular risk in psoriatic patients?.Ther Clin Risk Manag. 2019 Jul 5;15:831-837. doi: 10.2147/TCRM.S197633. eCollection 2019.
18	Effects of alpha1-acid glycoprotein on free radical oxidation processes in experimental liver failure.Bull Exp Biol Med. 2007 Jul;144(1):26-8. doi: 10.1007/s10517-007-0244-2.
19	Label-Free Quantitative Proteomics Identifies Novel Plasma Biomarkers for Distinguishing Pulmonary Tuberculosis and Latent Infection.Front Microbiol. 2018 Jun 13;9:1267. doi: 10.3389/fmicb.2018.01267. eCollection 2018.
20	The ORMDL3 asthma susceptibility gene regulates systemic ceramide levels without altering key asthma features in mice.J Allergy Clin Immunol. 2019 Dec;144(6):1648-1659.e9. doi: 10.1016/j.jaci.2019.06.041. Epub 2019 Jul 20.
21	Transcriptome Analysis Uncovers a Growth-Promoting Activity of Orosomucoid-1 on Hepatocytes.EBioMedicine. 2017 Oct;24:257-266. doi: 10.1016/j.ebiom.2017.09.008. Epub 2017 Sep 12.
22	Alpha-1-acid glycoprotein 1 is upregulated in pancreatic ductal adenocarcinoma and confers a poor prognosis.Transl Res. 2019 Oct;212:67-79. doi: 10.1016/j.trsl.2019.06.003. Epub 2019 Jun 29.
23	Genetic association analyses of atopic illness and proinflammatory cytokine genes with type 1 diabetes.Diabetes Metab Res Rev. 2011 Nov;27(8):838-43. doi: 10.1002/dmrr.1259.
24	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.
25	Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
26	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.
27	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
28	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.
29	Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
30	Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
31	A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
32	Binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main genetic variants of human alpha 1-acid glycoprotein: evidence for drug-binding differences between the variants and for the presence of two separate drug-binding sites on alpha 1-acid glycoprotein. Pharmacogenetics. 1996 Oct;6(5):403-15. doi: 10.1097/00008571-199610000-00004.
33	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.
34	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.
35	Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
36	Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
37	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.
38	Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
39	Identification of genes targeted by the androgen and PKA signaling pathways in prostate cancer cells. Oncogene. 2006 Nov 23;25(55):7311-23.
40	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.
41	Building individualized medicine: prevention of adverse reactions to warfarin therapy. J Pharmacol Exp Ther. 2007 Aug;322(2):427-34. doi: 10.1124/jpet.106.117952. Epub 2007 May 11.