Details of Drug Off-Target (DOT)

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

DOT Name Angiopoietin-like protein 8 (ANGPTL8)
Synonyms Betatrophin; Lipasin; Refeeding-induced fat and liver protein
Gene Name ANGPTL8
Related Disease
Intervertebral disc degeneration ( )
Metabolic disorder ( )
Non-alcoholic fatty liver disease ( )
Type-1 diabetes ( )
Coronary atherosclerosis ( )
Diabetic retinopathy ( )
Fatty liver disease ( )
Graves disease ( )
Hyperglycemia ( )
Hyperinsulinemia ( )
Hyperlipidemia ( )
Hypothyroidism ( )
Intrahepatic cholestasis of pregnancy ( )
Non-proliferative diabetic retinopathy ( )
Obstructive sleep apnea ( )
Peripheral arterial disease ( )
Polycystic ovarian syndrome ( )
Prediabetes syndrome ( )
Proliferative diabetic retinopathy ( )
Type-1/2 diabetes ( )
X-linked reticulate pigmentary disorder ( )
Cardiovascular disease ( )
High blood pressure ( )
Prader-Willi syndrome ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Cardiomyopathy ( )
Hepatocellular carcinoma ( )
Neoplasm ( )
UniProt ID
ANGL8_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MPVPALCLLWALAMVTRPASAAPMGGPELAQHEELTLLFHGTLQLGQALNGVYRTTEGRL
TKARNSLGLYGRTIELLGQEVSRGRDAAQELRASLLETQMEEDILQLQAEATAEVLGEVA
QAQKVLRDSVQRLEVQLRSAWLGPAYREFEVLKAHADKQSHILWALTGHVQRQRREMVAQ
QHRLRQIQERLHTAALPA
Function
Hormone that acts as a blood lipid regulator by regulating serum triglyceride levels. May be involved in the metabolic transition between fasting and refeeding: required to direct fatty acids to adipose tissue for storage in the fed state.
Tissue Specificity Predominantly expressed in liver. Also expressed in adipose tissues.
KEGG Pathway
Cholesterol metabolism (hsa04979 )
Reactome Pathway
Assembly of active LPL and LIPC lipase complexes (R-HSA-8963889 )

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Intervertebral disc degeneration DISG3AIM Definitive Altered Expression [1]
Metabolic disorder DIS71G5H Definitive Altered Expression [2]
Non-alcoholic fatty liver disease DISDG1NL Definitive Altered Expression [3]
Type-1 diabetes DIS7HLUB Definitive Altered Expression [1]
Coronary atherosclerosis DISKNDYU Strong Altered Expression [4]
Diabetic retinopathy DISHGUJM Strong Altered Expression [5]
Fatty liver disease DIS485QZ Strong Biomarker [6]
Graves disease DISU4KOQ Strong Biomarker [7]
Hyperglycemia DIS0BZB5 Strong Biomarker [8]
Hyperinsulinemia DISIDWT6 Strong Altered Expression [9]
Hyperlipidemia DIS61J3S Strong Altered Expression [10]
Hypothyroidism DISR0H6D Strong Biomarker [11]
Intrahepatic cholestasis of pregnancy DISMHS5F Strong Altered Expression [2]
Non-proliferative diabetic retinopathy DISPMG3Z Strong Altered Expression [10]
Obstructive sleep apnea DIS0SVD1 Strong Altered Expression [12]
Peripheral arterial disease DIS78WFB Strong Altered Expression [13]
Polycystic ovarian syndrome DISZ2BNG Strong Altered Expression [14]
Prediabetes syndrome DISH2I53 Strong Biomarker [15]
Proliferative diabetic retinopathy DISQZ13G Strong Biomarker [5]
Type-1/2 diabetes DISIUHAP Strong Genetic Variation [16]
X-linked reticulate pigmentary disorder DIS0RB5A Strong Altered Expression [5]
Cardiovascular disease DIS2IQDX moderate Biomarker [17]
High blood pressure DISY2OHH moderate Altered Expression [18]
Prader-Willi syndrome DISYWMLU moderate Altered Expression [19]
Arteriosclerosis DISK5QGC Limited Biomarker [13]
Atherosclerosis DISMN9J3 Limited Biomarker [13]
Cardiomyopathy DISUPZRG Limited Biomarker [20]
Hepatocellular carcinoma DIS0J828 Limited Biomarker [21]
Neoplasm DISZKGEW Limited Biomarker [21]
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⏷ Show the Full List of 29 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
7 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 Angiopoietin-like protein 8 (ANGPTL8). [22]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Angiopoietin-like protein 8 (ANGPTL8). [23]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Angiopoietin-like protein 8 (ANGPTL8). [24]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Angiopoietin-like protein 8 (ANGPTL8). [23]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Angiopoietin-like protein 8 (ANGPTL8). [25]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Angiopoietin-like protein 8 (ANGPTL8). [23]
OXYQUINOLINE DMZVS9Y Investigative OXYQUINOLINE decreases the expression of Angiopoietin-like protein 8 (ANGPTL8). [23]
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⏷ Show the Full List of 7 Drug(s)

References

1 Angiopoietin-like protein 8 expression and association with extracellular matrix metabolism and inflammation during intervertebral disc degeneration.J Cell Mol Med. 2019 Aug;23(8):5737-5750. doi: 10.1111/jcmm.14488. Epub 2019 Jun 18.
2 Assessment of circulating betatrophin levels in intrahepatic cholestasis of pregnancy.J Matern Fetal Neonatal Med. 2019 Dec;32(24):4067-4072. doi: 10.1080/14767058.2018.1481382. Epub 2018 Jun 11.
3 Regulation of angiopoietin-like protein 8 expression under different nutritional and metabolic status.Endocr J. 2019 Dec 25;66(12):1039-1046. doi: 10.1507/endocrj.EJ19-0263. Epub 2019 Oct 19.
4 Associations between circulating full-length angiopoietin-like protein 8 levels and severity of coronary artery disease in Chinese non-diabetic patients: a case-control study.Cardiovasc Diabetol. 2018 Jun 25;17(1):92. doi: 10.1186/s12933-018-0736-6.
5 Clinical and experimental study on angiopoietin-like protein 8 associated with proliferative diabetic retinopathy.Int J Ophthalmol. 2017 Dec 18;10(12):1819-1823. doi: 10.18240/ijo.2017.12.05. eCollection 2017.
6 Angptl8 antisense oligonucleotide improves adipose lipid metabolism and prevents diet-induced NAFLD and hepatic insulin resistance in rodents.Diabetologia. 2018 Jun;61(6):1435-1446. doi: 10.1007/s00125-018-4579-1. Epub 2018 Mar 1.
7 Decreased circulating levels of ANGPTL8 in Graves' disease patients.Hormones (Athens). 2019 Jun;18(2):189-195. doi: 10.1007/s42000-019-00095-8. Epub 2019 Mar 21.
8 Recombinant betatrophin (Angptl?/lipasin) ameliorates streptozotocininduced hyperglycemia and cell destruction in neonatal rats.Mol Med Rep. 2019 Nov;20(5):4523-4532. doi: 10.3892/mmr.2019.10719. Epub 2019 Oct 1.
9 Loss of Glycine N-Methyltransferase Associates with Angiopoietin-Like Protein 8 Expression in High Fat-Diet-Fed Mice.Int J Mol Sci. 2019 Aug 29;20(17):4223. doi: 10.3390/ijms20174223.
10 Expression of angiopoietin-like protein 8 correlates with VEGF in patients with proliferative diabetic retinopathy.Graefes Arch Clin Exp Ophthalmol. 2017 Aug;255(8):1515-1523. doi: 10.1007/s00417-017-3676-z. Epub 2017 Apr 29.
11 Circulating Angptl3 and Angptl8 Are Increased in Patients with Hypothyroidism.Biomed Res Int. 2019 Jul 17;2019:3814687. doi: 10.1155/2019/3814687. eCollection 2019.
12 Increased Level of Angiopoietin Like Proteins 4 and 8 in People With Sleep Apnea.Front Endocrinol (Lausanne). 2018 Nov 13;9:651. doi: 10.3389/fendo.2018.00651. eCollection 2018.
13 Associations Between Plasma Betatrophin Levels and Coronary and Peripheral Artery Disease.J Atheroscler Thromb. 2019 Jun 1;26(6):573-581. doi: 10.5551/jat.46508. Epub 2018 Dec 4.
14 Serum betatrophin levels are reduced in patients with full-blown polycystic ovary syndrome.Gynecol Endocrinol. 2019 Mar;35(3):224-227. doi: 10.1080/09513590.2018.1519791. Epub 2018 Sep 21.
15 Short-Term Cooling Increases Plasma ANGPTL3 and ANGPTL8 in Young Healthy Lean Men but Not in Middle-Aged Men with Overweight and Prediabetes.J Clin Med. 2019 Aug 14;8(8):1214. doi: 10.3390/jcm8081214.
16 Association between rs2278426 (C/T) and rs892066 (C/G) variants of ANGPTL8 (betatrophin) and susceptibility to type2 diabetes mellitus.J Clin Lab Anal. 2019 Jan;33(1):e22649. doi: 10.1002/jcla.22649. Epub 2018 Sep 7.
17 The potential role of angiopoietin-like protein-8 in type 2 diabetes mellitus: a possibility for predictive diagnosis and targeted preventive measures?.EPMA J. 2019 Aug 6;10(3):239-248. doi: 10.1007/s13167-019-00180-3. eCollection 2019 Sep.
18 Increased plasma and adipose tissue levels of ANGPTL8/Betatrophin and ANGPTL4 in people with hypertension.Lipids Health Dis. 2018 Mar 1;17(1):35. doi: 10.1186/s12944-018-0681-0.
19 Circulating angiopoietin-like 8 (ANGPTL8) is a marker of liver steatosis and is negatively regulated by Prader-Willi Syndrome.Sci Rep. 2017 Jun 9;7(1):3186. doi: 10.1038/s41598-017-03538-7.
20 ANGPTL8 reverses established adriamycin cardiomyopathy by stimulating adult cardiac progenitor cells.Oncotarget. 2016 Dec 6;7(49):80391-80403. doi: 10.18632/oncotarget.13061.
21 Hepatocellular Carcinoma-Associated Protein TD26 Interacts and Enhances Sterol Regulatory Element-Binding Protein 1 Activity to Promote Tumor Cell Proliferation and Growth.Hepatology. 2018 Nov;68(5):1833-1850. doi: 10.1002/hep.30030. Epub 2018 Sep 19.
22 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.
23 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.
24 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
25 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.