Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB6JG41)

DOT Name Angiopoietin-related protein 2 (ANGPTL2)
Synonyms Angiopoietin-like protein 2
Gene Name ANGPTL2
Related Disease
Prostate cancer ( )
Prostate carcinoma ( )
Schimke immuno-osseous dysplasia ( )
Adult glioblastoma ( )
Advanced cancer ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Bone osteosarcoma ( )
Breast neoplasm ( )
Cardiac failure ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Congestive heart failure ( )
Dermatomyositis ( )
Diabetic kidney disease ( )
Gastric cancer ( )
Glioblastoma multiforme ( )
Hepatocellular carcinoma ( )
Hirschsprung disease ( )
Inflammation ( )
Melanoma ( )
Metastatic malignant neoplasm ( )
Myocardial infarction ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
Non-small-cell lung cancer ( )
Obesity ( )
Osteosarcoma ( )
Polycystic ovarian syndrome ( )
Schizophrenia ( )
Type-1/2 diabetes ( )
Breast cancer ( )
Breast carcinoma ( )
Epithelial ovarian cancer ( )
Glioma ( )
Osteoarthritis ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Wiskott-Aldrich syndrome ( )
Acute coronary syndrome ( )
Coronary heart disease ( )
Cardiovascular disease ( )
Coronary atherosclerosis ( )
Pancreatic cancer ( )
Premature aging syndrome ( )
Stomach cancer ( )
UniProt ID
ANGL2_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
6Y41
Pfam ID
PF00147
Sequence
MRPLCVTCWWLGLLAAMGAVAGQEDGFEGTEEGSPREFIYLNRYKRAGESQDKCTYTFIV
PQQRVTGAICVNSKEPEVLLENRVHKQELELLNNELLKQKRQIETLQQLVEVDGGIVSEV
KLLRKESRNMNSRVTQLYMQLLHEIIRKRDNALELSQLENRILNQTADMLQLASKYKDLE
HKYQHLATLAHNQSEIIAQLEEHCQRVPSARPVPQPPPAAPPRVYQPPTYNRIINQISTN
EIQSDQNLKVLPPPLPTMPTLTSLPSSTDKPSGPWRDCLQALEDGHDTSSIYLVKPENTN
RLMQVWCDQRHDPGGWTVIQRRLDGSVNFFRNWETYKQGFGNIDGEYWLGLENIYWLTNQ
GNYKLLVTMEDWSGRKVFAEYASFRLEPESEYYKLRLGRYHGNAGDSFTWHNGKQFTTLD
RDHDVYTGNCAHYQKGGWWYNACAHSNLNGVWYRGGHYRSRYQDGVYWAEFRGGSYSLKK
VVMMIRPNPNTFH
Function Induces sprouting in endothelial cells through an autocrine and paracrine action.
Tissue Specificity Widely expressed in heart, small intestine, spleen and stomach. Also found in lower levels in colon, ovary, adrenal gland, skeletal muscle and in prostate.

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Prostate cancer DISF190Y Definitive Altered Expression [1]
Prostate carcinoma DISMJPLE Definitive Altered Expression [1]
Schimke immuno-osseous dysplasia DISGEL3Z Definitive Genetic Variation [2]
Adult glioblastoma DISVP4LU Strong Biomarker [3]
Advanced cancer DISAT1Z9 Strong Biomarker [4]
Arteriosclerosis DISK5QGC Strong Biomarker [5]
Atherosclerosis DISMN9J3 Strong Biomarker [5]
Bone osteosarcoma DIST1004 Strong Biomarker [6]
Breast neoplasm DISNGJLM Strong Biomarker [7]
Cardiac failure DISDC067 Strong Biomarker [8]
Colon cancer DISVC52G Strong Altered Expression [9]
Colon carcinoma DISJYKUO Strong Altered Expression [9]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [10]
Congestive heart failure DIS32MEA Strong Biomarker [8]
Dermatomyositis DIS50C5O Strong Biomarker [11]
Diabetic kidney disease DISJMWEY Strong Biomarker [12]
Gastric cancer DISXGOUK Strong Biomarker [13]
Glioblastoma multiforme DISK8246 Strong Biomarker [3]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [14]
Hirschsprung disease DISUUSM1 Strong Biomarker [15]
Inflammation DISJUQ5T Strong Genetic Variation [16]
Melanoma DIS1RRCY Strong Biomarker [17]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [10]
Myocardial infarction DIS655KI Strong Altered Expression [18]
Neoplasm DISZKGEW Strong Biomarker [17]
Non-insulin dependent diabetes DISK1O5Z Strong Biomarker [5]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [19]
Obesity DIS47Y1K Strong Biomarker [20]
Osteosarcoma DISLQ7E2 Strong Biomarker [6]
Polycystic ovarian syndrome DISZ2BNG Strong Altered Expression [21]
Schizophrenia DISSRV2N Strong Genetic Variation [22]
Type-1/2 diabetes DISIUHAP Strong Altered Expression [23]
Breast cancer DIS7DPX1 moderate Biomarker [24]
Breast carcinoma DIS2UE88 moderate Biomarker [24]
Epithelial ovarian cancer DIS56MH2 moderate Posttranslational Modification [25]
Glioma DIS5RPEH moderate Biomarker [26]
Osteoarthritis DIS05URM moderate Altered Expression [27]
Ovarian cancer DISZJHAP moderate Posttranslational Modification [25]
Ovarian neoplasm DISEAFTY moderate Posttranslational Modification [25]
Wiskott-Aldrich syndrome DISATMDB moderate Biomarker [28]
Acute coronary syndrome DIS7DYEW Disputed Genetic Variation [29]
Coronary heart disease DIS5OIP1 Disputed Posttranslational Modification [29]
Cardiovascular disease DIS2IQDX Limited Altered Expression [30]
Coronary atherosclerosis DISKNDYU Limited Biomarker [18]
Pancreatic cancer DISJC981 Limited Altered Expression [31]
Premature aging syndrome DIS51AGT Limited Biomarker [32]
Stomach cancer DISKIJSX Limited Biomarker [13]
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⏷ Show the Full List of 47 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
13 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-related protein 2 (ANGPTL2). [33]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Angiopoietin-related protein 2 (ANGPTL2). [34]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Angiopoietin-related protein 2 (ANGPTL2). [35]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Angiopoietin-related protein 2 (ANGPTL2). [36]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Angiopoietin-related protein 2 (ANGPTL2). [37]
Triclosan DMZUR4N Approved Triclosan increases the expression of Angiopoietin-related protein 2 (ANGPTL2). [38]
Cytarabine DMZD5QR Approved Cytarabine decreases the expression of Angiopoietin-related protein 2 (ANGPTL2). [39]
Dasatinib DMJV2EK Approved Dasatinib increases the expression of Angiopoietin-related protein 2 (ANGPTL2). [40]
Malathion DMXZ84M Approved Malathion decreases the expression of Angiopoietin-related protein 2 (ANGPTL2). [41]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Angiopoietin-related protein 2 (ANGPTL2). [42]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Angiopoietin-related protein 2 (ANGPTL2). [44]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Angiopoietin-related protein 2 (ANGPTL2). [45]
Deguelin DMXT7WG Investigative Deguelin decreases the expression of Angiopoietin-related protein 2 (ANGPTL2). [47]
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⏷ Show the Full List of 13 Drug(s)
2 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 Angiopoietin-related protein 2 (ANGPTL2). [43]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Angiopoietin-related protein 2 (ANGPTL2). [46]
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References

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3 HARP111-136 enhances radiation-induced apoptosis of U87MG glioblastoma by induction of the proapoptotic protein CHOP.Int J Oncol. 2011 Jan;38(1):179-88.
4 Benproperine, an ARPC2 inhibitor, suppresses cancer cell migration and tumor metastasis.Biochem Pharmacol. 2019 May;163:46-59. doi: 10.1016/j.bcp.2019.01.017. Epub 2019 Jan 30.
5 Association of serum angiopoietin-like protein 2 with elevated risk of cardiovascular diseases in subjects with type 2 diabetes.J Diabetes Complications. 2019 Nov;33(11):107421. doi: 10.1016/j.jdiacomp.2019.107421. Epub 2019 Aug 22.
6 Angiopoietin-like protein 2 is an important facilitator of tumor proliferation, metastasis, angiogenesis and glycolysis in osteosarcoma.Am J Transl Res. 2019 Oct 15;11(10):6341-6355. eCollection 2019.
7 ANGPTL2 increases bone metastasis of breast cancer cells through enhancing CXCR4 signaling.Sci Rep. 2015 Mar 16;5:9170. doi: 10.1038/srep09170.
8 Circulating ANGPTL2 Levels Increase in Humans and Mice Exhibiting Cardiac Dysfunction.Circ J. 2018 Jan 25;82(2):437-447. doi: 10.1253/circj.CJ-17-0327. Epub 2017 Sep 8.
9 Colon cancer-derived myofibroblasts increase endothelial cell migration by glucocorticoid-sensitive secretion of a pro-migratory factor.Vascul Pharmacol. 2017 Feb;89:19-30. doi: 10.1016/j.vph.2016.10.004. Epub 2016 Oct 4.
10 Serum Angiopoietin-like Protein 2 Improves Preoperative Detection of Lymph Node Metastasis in Colorectal Cancer.Anticancer Res. 2015 May;35(5):2849-56.
11 The role of angiopoietin-like protein 2 in pathogenesis of dermatomyositis.Biochem Biophys Res Commun. 2012 Feb 17;418(3):494-9. doi: 10.1016/j.bbrc.2012.01.052. Epub 2012 Jan 18.
12 Chronic Inflammation and Progression of Diabetic Kidney Disease.Contrib Nephrol. 2019;198:33-39. doi: 10.1159/000496526. Epub 2019 Apr 16.
13 Clinicopathological and prognostic significance of aberrant Arpin expression in gastric cancer.World J Gastroenterol. 2017 Feb 28;23(8):1450-1457. doi: 10.3748/wjg.v23.i8.1450.
14 Diagnostic value of angiopoietin-like protein 2 for CHB-related hepatocellular carcinoma.Cancer Manag Res. 2019 Jul 29;11:7159-7169. doi: 10.2147/CMAR.S217170. eCollection 2019.
15 MPGES-1 derived PGE2 inhibits cell migration by regulating ARP2/3 in the pathogenesis of Hirschsprung disease.J Pediatr Surg. 2019 Oct;54(10):2032-2037. doi: 10.1016/j.jpedsurg.2019.01.001. Epub 2019 Feb 24.
16 Loss of the Arp2/3 complex component ARPC1B causes platelet abnormalities and predisposes to inflammatory disease.Nat Commun. 2017 Apr 3;8:14816. doi: 10.1038/ncomms14816.
17 Dual functions of angiopoietin-like protein 2 signaling in tumor progression and anti-tumor immunity.Genes Dev. 2019 Dec 1;33(23-24):1641-1656. doi: 10.1101/gad.329417.119. Epub 2019 Nov 14.
18 Correlation between angiopoietin-like proteins in inflammatory mediators in peripheral blood and severity of coronary arterial lesion in patients with acute myocardial infarction.Exp Ther Med. 2019 May;17(5):3495-3500. doi: 10.3892/etm.2019.7386. Epub 2019 Mar 13.
19 Angiopoietin-like protein 2 facilitates non-small cell lung cancer progression by promoting the polarization of M2 tumor-associated macrophages.Am J Cancer Res. 2017 Nov 1;7(11):2220-2233. eCollection 2017.
20 Knockdown of angiopoietin-like 2 mimics the benefits of intermittent fasting on insulin responsiveness and weight loss.Exp Biol Med (Maywood). 2018 Jan;243(1):45-49. doi: 10.1177/1535370217745505. Epub 2017 Dec 1.
21 Serum Levels of Angiopoietin-Like Protein 2 and Obestatin in Iranian Women with Polycystic Ovary Syndrome and Normal Body Mass Index.J Clin Med. 2018 Jun 22;7(7):159. doi: 10.3390/jcm7070159.
22 Altered Expression of ARP2/3 Complex Signaling Pathway Genes in Prefrontal Layer 3 Pyramidal Cells in Schizophrenia.Am J Psychiatry. 2017 Feb 1;174(2):163-171. doi: 10.1176/appi.ajp.2016.16020204. Epub 2016 Aug 13.
23 Angiopoietin-Like Protein 2 Promotes the Progression of Diabetic Kidney Disease.J Clin Endocrinol Metab. 2019 Jan 1;104(1):172-180. doi: 10.1210/jc.2017-02705.
24 Breast cancer induced nociceptor aberrant growth and collateral sensory axonal branching.Oncotarget. 2017 Sep 1;8(44):76606-76621. doi: 10.18632/oncotarget.20609. eCollection 2017 Sep 29.
25 Frequent inactivation of a putative tumor suppressor, angiopoietin-like protein 2, in ovarian cancer.Cancer Res. 2008 Jul 1;68(13):5067-75. doi: 10.1158/0008-5472.CAN-08-0062.
26 Knockdown of Angiopoietin-Like Protein 2 Inhibits Proliferation and Invasion in Glioma Cells via Suppressing the ERK/MAPK Signaling Pathway.Oncol Res. 2017 Sep 21;25(8):1349-1355. doi: 10.3727/096504017X14874337324615. Epub 2017 Feb 28.
27 Angiopoietin-like 2 upregulation promotes human chondrocyte injury via NF-B and p38/MAPK signaling pathway.J Bone Miner Metab. 2019 Nov;37(6):976-986. doi: 10.1007/s00774-019-01016-w. Epub 2019 Jun 18.
28 Single-Turnover Activation of Arp2/3 Complex by Dip1 May Balance Nucleation of Linear versus Branched Actin Filaments.Curr Biol. 2019 Oct 7;29(19):3331-3338.e7. doi: 10.1016/j.cub.2019.08.023. Epub 2019 Sep 26.
29 Preliminary study of the relationship between promoter methylation of the ANGPTL2 gene and coronary heart disease.J Clin Lab Anal. 2019 Mar;33(3):e22702. doi: 10.1002/jcla.22702. Epub 2018 Nov 21.
30 Reduction of plasma angiopoietin-like 2 after cardiac surgery is related to tissue inflammation and senescence status of patients.J Thorac Cardiovasc Surg. 2019 Sep;158(3):792-802.e5. doi: 10.1016/j.jtcvs.2018.12.047. Epub 2019 Jan 8.
31 Angiopoietin-like Protein 2 is a Useful Biomarker for Pancreatic Cancer that is Associated with Type 2 Diabetes Mellitus and Inflammation.J Cancer. 2018 Nov 25;9(24):4736-4741. doi: 10.7150/jca.25404. eCollection 2018.
32 Circulating angiopoietin-like protein 2 levels and mortality risk in patients receiving maintenance hemodialysis: a prospective cohort study.Nephrol Dial Transplant. 2020 May 1;35(5):854-860. doi: 10.1093/ndt/gfz236.
33 Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
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38 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
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41 Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
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