Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA58CED)

DOT Name Apolipoprotein C-I (APOC1)
Synonyms Apo-CI; ApoC-I; Apolipoprotein C1
Gene Name APOC1
Related Disease
Gastric cancer ( )
Multiple sclerosis ( )
Neoplasm ( )
Stomach cancer ( )
Acute megakaryoblastic leukemia ( )
Advanced cancer ( )
Alopecia ( )
Alzheimer disease ( )
Atherosclerosis ( )
Autism spectrum disorder ( )
Behavioral variant of frontotemporal dementia ( )
Cardiac disease ( )
Cardiac failure ( )
Cardiovascular disease ( )
Cholelithiasis ( )
Colorectal adenocarcinoma ( )
Colorectal carcinoma ( )
Congestive heart failure ( )
Diabetic kidney disease ( )
Dysbetalipoproteinemia ( )
Familial Alzheimer disease ( )
Fatty liver disease ( )
Fibromyalgia ( )
Frontotemporal dementia ( )
Glomerulosclerosis ( )
Hepatitis C virus infection ( )
High blood pressure ( )
Hyperinsulinemia ( )
Invasive ductal breast carcinoma ( )
Myotonic dystrophy ( )
Nephropathy ( )
Neuralgia ( )
Pancreatic cancer ( )
Pancreatic ductal carcinoma ( )
Pancreatic tumour ( )
Pick disease ( )
Primary progressive aphasia ( )
Prostate cancer ( )
Prostate carcinoma ( )
Atopic dermatitis ( )
Coronary atherosclerosis ( )
Dementia ( )
Neuroblastoma ( )
Obesity ( )
Polycystic ovarian syndrome ( )
UniProt ID
APOC1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1ALE; 1ALF; 1IOJ; 1OPP; 6DVU; 6DXR; 6DZ6; 6NF3
Pfam ID
PF04691
Sequence
MRLFLSLPVLVVVLSIVLEGPAPAQGTPDVSSALDKLKEFGNTLEDKARELISRIKQSEL
SAKMREWFSETFQKVKEKLKIDS
Function
Inhibitor of lipoprotein binding to the low density lipoprotein (LDL) receptor, LDL receptor-related protein, and very low density lipoprotein (VLDL) receptor. Associates with high density lipoproteins (HDL) and the triacylglycerol-rich lipoproteins in the plasma and makes up about 10% of the protein of the VLDL and 2% of that of HDL. Appears to interfere directly with fatty acid uptake and is also the major plasma inhibitor of cholesteryl ester transfer protein (CETP). Binds free fatty acids and reduces their intracellular esterification. Modulates the interaction of APOE with beta-migrating VLDL and inhibits binding of beta-VLDL to the LDL receptor-related protein.
Tissue Specificity Synthesized mainly in liver and to a minor degree in intestine. Also found in the lung and spleen.
KEGG Pathway
Cholesterol metabolism (hsa04979 )
Reactome Pathway
VLDL clearance (R-HSA-8964046 )
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux (R-HSA-9029569 )
VLDL assembly (R-HSA-8866423 )

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Gastric cancer DISXGOUK Definitive Altered Expression [1]
Multiple sclerosis DISB2WZI Definitive Biomarker [2]
Neoplasm DISZKGEW Definitive Altered Expression [1]
Stomach cancer DISKIJSX Definitive Altered Expression [1]
Acute megakaryoblastic leukemia DIS0JX3M Strong Biomarker [3]
Advanced cancer DISAT1Z9 Strong Biomarker [4]
Alopecia DIS37HU4 Strong Biomarker [5]
Alzheimer disease DISF8S70 Strong Genetic Variation [6]
Atherosclerosis DISMN9J3 Strong Altered Expression [7]
Autism spectrum disorder DISXK8NV Strong Biomarker [8]
Behavioral variant of frontotemporal dementia DISQHX2V Strong Genetic Variation [9]
Cardiac disease DISVO1I5 Strong Biomarker [10]
Cardiac failure DISDC067 Strong Biomarker [11]
Cardiovascular disease DIS2IQDX Strong Biomarker [12]
Cholelithiasis DISERLZB Strong Genetic Variation [13]
Colorectal adenocarcinoma DISPQOUB Strong Biomarker [4]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [4]
Congestive heart failure DIS32MEA Strong Biomarker [11]
Diabetic kidney disease DISJMWEY Strong Genetic Variation [14]
Dysbetalipoproteinemia DISNRSNM Strong Genetic Variation [15]
Familial Alzheimer disease DISE75U4 Strong Biomarker [16]
Fatty liver disease DIS485QZ Strong Altered Expression [17]
Fibromyalgia DISZJDS2 Strong Altered Expression [18]
Frontotemporal dementia DISKYHXL Strong Biomarker [9]
Glomerulosclerosis DISJF20Z Strong Altered Expression [19]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [20]
High blood pressure DISY2OHH Strong Biomarker [21]
Hyperinsulinemia DISIDWT6 Strong Altered Expression [21]
Invasive ductal breast carcinoma DIS43J58 Strong Genetic Variation [22]
Myotonic dystrophy DISNBEMX Strong Biomarker [23]
Nephropathy DISXWP4P Strong Genetic Variation [19]
Neuralgia DISWO58J Strong Altered Expression [18]
Pancreatic cancer DISJC981 Strong Biomarker [22]
Pancreatic ductal carcinoma DIS26F9Q Strong Genetic Variation [22]
Pancreatic tumour DIS3U0LK Strong Altered Expression [24]
Pick disease DISP6X50 Strong Biomarker [9]
Primary progressive aphasia DISLRYFE Strong Genetic Variation [9]
Prostate cancer DISF190Y Strong Biomarker [25]
Prostate carcinoma DISMJPLE Strong Biomarker [25]
Atopic dermatitis DISTCP41 Limited Biomarker [26]
Coronary atherosclerosis DISKNDYU Limited Genetic Variation [27]
Dementia DISXL1WY Limited Genetic Variation [28]
Neuroblastoma DISVZBI4 Limited Biomarker [29]
Obesity DIS47Y1K Limited Biomarker [30]
Polycystic ovarian syndrome DISZ2BNG Limited Genetic Variation [31]
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⏷ Show the Full List of 45 Disease(s)
Molecular Interaction Atlas (MIA) 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
Fluorouracil DMUM7HZ Approved Apolipoprotein C-I (APOC1) affects the response to substance of Fluorouracil. [48]
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17 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 Apolipoprotein C-I (APOC1). [32]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Apolipoprotein C-I (APOC1). [33]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Apolipoprotein C-I (APOC1). [34]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Apolipoprotein C-I (APOC1). [35]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Apolipoprotein C-I (APOC1). [36]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of Apolipoprotein C-I (APOC1). [37]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Apolipoprotein C-I (APOC1). [38]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Apolipoprotein C-I (APOC1). [39]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Apolipoprotein C-I (APOC1). [37]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of Apolipoprotein C-I (APOC1). [40]
Mifepristone DMGZQEF Approved Mifepristone decreases the expression of Apolipoprotein C-I (APOC1). [41]
Capsaicin DMGMF6V Approved Capsaicin decreases the expression of Apolipoprotein C-I (APOC1). [42]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Apolipoprotein C-I (APOC1). [43]
Resveratrol DM3RWXL Phase 3 Resveratrol increases the expression of Apolipoprotein C-I (APOC1). [44]
Belinostat DM6OC53 Phase 2 Belinostat decreases the expression of Apolipoprotein C-I (APOC1). [39]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Apolipoprotein C-I (APOC1). [46]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Apolipoprotein C-I (APOC1). [47]
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⏷ Show the Full List of 17 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Apolipoprotein C-I (APOC1). [45]
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References

1 Apolipoprotein C1 (APOC1) as a novel diagnostic and prognostic biomarker for gastric cancer.Ann Transl Med. 2019 Aug;7(16):380. doi: 10.21037/atm.2019.07.59.
2 APOE genotypes in African American female multiple sclerosis patients.Neurosci Lett. 2007 Feb 27;414(1):51-6. doi: 10.1016/j.neulet.2006.12.049. Epub 2007 Jan 7.
3 Distinct gene signatures of transient and acute megakaryoblastic leukemia in Down syndrome.Leukemia. 2004 Oct;18(10):1617-23. doi: 10.1038/sj.leu.2403466.
4 Apolipoprotein C1 (APOC1) promotes tumor progression via MAPK signaling pathways in colorectal cancer.Cancer Manag Res. 2019 May 29;11:4917-4930. doi: 10.2147/CMAR.S192529. eCollection 2019.
5 Hyperlipidemia and cutaneous abnormalities in transgenic mice overexpressing human apolipoprotein C1.J Clin Invest. 1998 Jan 1;101(1):145-52. doi: 10.1172/JCI791.
6 Association between selected cholesterol-related gene polymorphisms and Alzheimer's disease in a Turkish cohort.Mol Biol Rep. 2019 Apr;46(2):1701-1707. doi: 10.1007/s11033-019-04619-8. Epub 2019 Jan 25.
7 Apolipoprotein C1 and apolipoprotein E are differentially expressed in atheroma of the carotid and femoral artery.J Surg Res. 2008 Jan;144(1):132-7. doi: 10.1016/j.jss.2007.02.009. Epub 2007 Oct 22.
8 Peptidome Analysis Reveals Novel Serum Biomarkers for Children with Autism Spectrum Disorder in China.Proteomics Clin Appl. 2018 Sep;12(5):e1700164. doi: 10.1002/prca.201700164. Epub 2018 May 30.
9 TOMM40, APOE, and APOC1 in primary progressive aphasia and frontotemporal dementia.J Alzheimers Dis. 2012;31(4):731-40. doi: 10.3233/JAD-2012-120403.
10 Apolipoprotein C-I genotype and serum levels of triglycerides, C-reactive protein and coronary heart disease.Metabolism. 2010 Dec;59(12):1736-41. doi: 10.1016/j.metabol.2010.04.017. Epub 2010 Jul 2.
11 Inhibition of G-protein-coupled Receptor Kinase 2 Prevents the Dysfunctional Cardiac Substrate Metabolism in Fatty Acid Synthase Transgenic Mice. J Biol Chem. 2016 Feb 5;291(6):2583-600. doi: 10.1074/jbc.M115.702688. Epub 2015 Dec 15.
12 The use of network analyses for elucidating mechanisms in cardiovascular disease.Mol Biosyst. 2010 Feb;6(2):289-304. doi: 10.1039/b912078e. Epub 2009 Oct 16.
13 Association of APOE-C1 gene cluster polymorphisms with gallstone disease.Dig Liver Dis. 2006 Jun;38(6):397-403. doi: 10.1016/j.dld.2006.02.005. Epub 2006 May 2.
14 Association analysis of dyslipidemia-related genes in diabetic nephropathy.PLoS One. 2013;8(3):e58472. doi: 10.1371/journal.pone.0058472. Epub 2013 Mar 26.
15 Exact localization of the familial dysbetalipoproteinemia associated HpaI restriction site in the promoter region of the APOC1 gene.Biochem Biophys Res Commun. 1988 May 16;152(3):1282-8. doi: 10.1016/s0006-291x(88)80424-8.
16 Hidden heterogeneity in Alzheimer's disease: Insights from genetic association studies and other analyses.Exp Gerontol. 2018 Jul 1;107:148-160. doi: 10.1016/j.exger.2017.10.020. Epub 2017 Oct 26.
17 Overexpression of APOC1 in obob mice leads to hepatic steatosis and severe hepatic insulin resistance.J Lipid Res. 2004 Jan;45(1):9-16. doi: 10.1194/jlr.M300240-JLR200. Epub 2003 Oct 1.
18 CSF levels of apolipoprotein C1 and autotaxin found to associate with neuropathic pain and fibromyalgia.J Pain Res. 2019 Oct 15;12:2875-2889. doi: 10.2147/JPR.S215348. eCollection 2019.
19 Apolipoprotein C-I plays a role in the pathogenesis of glomerulosclerosis.J Pathol. 2017 Apr;241(5):589-599. doi: 10.1002/path.4859. Epub 2017 Feb 2.
20 Characterization of apolipoprotein C1 in hepatitis C virus infection and morphogenesis.Virology. 2018 Nov;524:1-9. doi: 10.1016/j.virol.2018.08.004. Epub 2018 Aug 18.
21 Hyperlipidaemia is associated with increased insulin-mediated glucose metabolism, reduced fatty acid metabolism and normal blood pressure in transgenic mice overexpressing human apolipoprotein C1.Diabetologia. 2001 Apr;44(4):437-43. doi: 10.1007/s001250051641.
22 Stromal responses to carcinomas of the pancreas: juxtatumoral gene expression conforms to the infiltrating pattern and not the biologic subtype.Cancer Biol Ther. 2005 Mar;4(3):302-7. doi: 10.4161/cbt.4.3.1501. Epub 2005 Mar 23.
23 Linkage relationships of the apolipoprotein C1 gene and a cytochrome P450 gene (CYP2A) to myotonic dystrophy.Hum Genet. 1990 Aug;85(3):305-10. doi: 10.1007/BF00206751.
24 Apolipoprotein C-1 maintains cell survival by preventing from apoptosis in pancreatic cancer cells.Oncogene. 2008 May 1;27(20):2810-22. doi: 10.1038/sj.onc.1210951. Epub 2007 Nov 26.
25 Apolipoprotein C1 promotes prostate cancer cell proliferation in vitro.J Biochem Mol Toxicol. 2018 May 2;32(7):e22158. doi: 10.1002/jbt.22158. Online ahead of print.
26 Lactobacillus plantarum NCIMB8826 ameliorates inflammation of colon and skin in human APOC1 transgenic mice.Benef Microbes. 2016;7(2):215-25. doi: 10.3920/BM2015.0074. Epub 2015 Dec 21.
27 Isoforms of apolipoprotein C-I associated with individuals with coronary artery disease.Biochem Biophys Res Commun. 2011 Jan 28;404(4):1034-8. doi: 10.1016/j.bbrc.2010.12.105. Epub 2010 Dec 25.
28 DNA methylation in the APOE genomic region is associated with cognitive function in African Americans.BMC Med Genomics. 2018 May 8;11(1):43. doi: 10.1186/s12920-018-0363-9.
29 Truncated apolipoprotein C-I induces apoptosis in neuroblastoma by activating caspases in the extrinsic and intrinsic pathways.Oncol Rep. 2017 Sep;38(3):1797-1805. doi: 10.3892/or.2017.5819. Epub 2017 Jul 14.
30 Apolipoprotein C-I binds free fatty acids and reduces their intracellular esterification.J Lipid Res. 2007 Jun;48(6):1353-61. doi: 10.1194/jlr.M700024-JLR200. Epub 2007 Mar 5.
31 Effects of apoC1 genotypes on the hormonal levels, metabolic profile and PAF-AH activity in Chinese women with polycystic ovary syndrome.Lipids Health Dis. 2018 Apr 10;17(1):77. doi: 10.1186/s12944-018-0725-5.
32 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
33 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.
34 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
35 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
36 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
37 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
38 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.
39 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.
40 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
41 Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
42 Induction of the endoplasmic reticulum stress protein GADD153/CHOP by capsaicin in prostate PC-3 cells: a microarray study. Biochem Biophys Res Commun. 2008 Aug 8;372(4):785-91.
43 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
44 A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer. Toxicol Appl Pharmacol. 2015 Jun 1;285(2):79-88.
45 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.
46 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
47 Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
48 Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.