Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX3GUHB)

DOT Name	Cortistatin (CORT)
Gene Name	CORT
Related Disease	Arthritis ( ) Cognitive impairment ( ) Abdominal aortic aneurysm ( ) Acute myocardial infarction ( ) Arteriosclerosis ( ) Atherosclerosis ( ) Autoimmune disease ( ) Behcet disease ( ) Breast cancer ( ) Breast carcinoma ( ) Cardiovascular disease ( ) Cyclic hematopoiesis ( ) Diabetic retinopathy ( ) Hepatocellular carcinoma ( ) Major depressive disorder ( ) Mixed anxiety and depressive disorder ( ) Neoplasm ( ) Obesity ( ) Type-1/2 diabetes ( ) Adrenocortical insufficiency ( ) Neuroblastoma ( ) Acute myelogenous leukaemia ( ) Asthma ( ) Advanced cancer ( ) Anxiety ( ) Anxiety disorder ( ) Colitis ( ) Coronary atherosclerosis ( ) Coronary heart disease ( ) Depression ( ) Non-insulin dependent diabetes ( ) Osteoarthritis ( ) Post-traumatic stress disorder ( ) Schizophrenia ( ) Vascular disease ( )
UniProt ID	CORT_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	7S8L; 7S8M; 7VDL; 7VV4
Pfam ID	PF03002
Sequence	MPLSPGLLLLLLSGATATAALPLEGGPTGRDSEHMQEAAGIRKSSLLTFLAWWFEWTSQA SAGPLIGEEAREVARRQEGAPPQQSARRDRMPCRNFFWKTFSSCK
Function	Binds to all human somatostatin receptor (SSTR) subtypes. It also inhibits cAMP production induced by forskolin through SSTRs.
Tissue Specificity	Expressed in a subset of GABAergic cells in the cortex and hippocampus.
KEGG Pathway	Neuroactive ligand-receptor interaction (hsa04080 )
Reactome Pathway	G alpha (i) signalling events (R-HSA-418594 ) Peptide ligand-binding receptors (R-HSA-375276 )

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Arthritis	DIST1YEL	Definitive	Biomarker	[1]
Cognitive impairment	DISH2ERD	Definitive	Altered Expression	[2]
Abdominal aortic aneurysm	DISD06OF	Strong	Biomarker	[3]
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[4]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[5]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[5]
Autoimmune disease	DISORMTM	Strong	Altered Expression	[5]
Behcet disease	DISSYMBS	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[8]
Cyclic hematopoiesis	DISQQOM4	Strong	Altered Expression	[9]
Diabetic retinopathy	DISHGUJM	Strong	Altered Expression	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[11]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[12]
Mixed anxiety and depressive disorder	DISV809X	Strong	Biomarker	[13]
Neoplasm	DISZKGEW	Strong	Altered Expression	[14]
Obesity	DIS47Y1K	Strong	Biomarker	[7]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[10]
Adrenocortical insufficiency	DISZ0CPT	moderate	Biomarker	[15]
Neuroblastoma	DISVZBI4	moderate	Genetic Variation	[16]
Acute myelogenous leukaemia	DISCSPTN	Disputed	Genetic Variation	[17]
Asthma	DISW9QNS	Disputed	Posttranslational Modification	[18]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[14]
Anxiety	DISIJDBA	Limited	Biomarker	[19]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[19]
Colitis	DISAF7DD	Limited	Altered Expression	[20]
Coronary atherosclerosis	DISKNDYU	Limited	Biomarker	[21]
Coronary heart disease	DIS5OIP1	Limited	Biomarker	[21]
Depression	DIS3XJ69	Limited	Altered Expression	[22]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Altered Expression	[23]
Osteoarthritis	DIS05URM	Limited	Biomarker	[24]
Post-traumatic stress disorder	DISHL1EY	Limited	Biomarker	[25]
Schizophrenia	DISSRV2N	Limited	Altered Expression	[25]
Vascular disease	DISVS67S	Limited	Biomarker	[21]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cortistatin (CORT).	[26]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cortistatin (CORT).	[28]
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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 affects the methylation of Cortistatin (CORT).	[27]
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References

1	Berberine ameliorates collagen-induced arthritis in rats by suppressing Th17 cell responses via inducing cortistatin in the gut.FEBS J. 2017 Sep;284(17):2786-2801. doi: 10.1111/febs.14147. Epub 2017 Jul 14.
2	Targeting glucocorticoid receptors prevents the effects of early life stress on amyloid pathology and cognitive performance in APP/PS1 mice.Transl Psychiatry. 2018 Mar 1;8(1):53. doi: 10.1038/s41398-018-0101-2.
3	Cortistatin attenuates angiotensin II-induced abdominal aortic aneurysm through inactivation of the ERK1/2 signaling pathways.Biochem Biophys Res Commun. 2018 Jan 8;495(2):1801-1806. doi: 10.1016/j.bbrc.2017.12.033. Epub 2017 Dec 7.
4	Cortistatin Improves Cardiac Function After Acute Myocardial Infarction in Rats by Suppressing Myocardial Apoptosis and Endoplasmic Reticulum Stress.J Cardiovasc Pharmacol Ther. 2017 Jan;22(1):83-93. doi: 10.1177/1074248416644988. Epub 2016 Jun 23.
5	Cortistatin reduces atherosclerosis in hyperlipidemic ApoE-deficient mice and the formation of foam cells.Sci Rep. 2017 Apr 13;7:46444. doi: 10.1038/srep46444.
6	Serum Cortistatin Levels in Patients with Ocular Active and Ocular Inactive Behet Disease.Ocul Immunol Inflamm. 2020 May 18;28(4):601-605. doi: 10.1080/09273948.2019.1610461. Epub 2019 Jul 17.
7	Lack of cortistatin or somatostatin differentially influences DMBA-induced mammary gland tumorigenesis in mice in an obesity-dependent mode.Breast Cancer Res. 2016 Mar 8;18(1):29. doi: 10.1186/s13058-016-0689-1.
8	Cortistatin exerts antiproliferation and antimigration effects in vascular smooth muscle cells stimulated by Ang II through suppressing ERK1/2, p38 MAPK, JNK and ERK5 signaling pathways.Ann Transl Med. 2019 Oct;7(20):561. doi: 10.21037/atm.2019.09.45.
9	17-Estradiol is required for the sexually dimorphic effects of repeated binge-pattern alcohol exposure on the HPA axis during adolescence.PLoS One. 2012;7(2):e32263. doi: 10.1371/journal.pone.0032263. Epub 2012 Feb 22.
10	Evaluation of aqueous humor and serum cortistatin levels in diabetic patients with and without diabetic retinopathy.Eur J Ophthalmol. 2021 Mar;31(2):638-642. doi: 10.1177/1120672119894847. Epub 2019 Dec 10.
11	Cortistatin production by HepG2 human hepatocellular carcinoma cell line and distribution of somatostatin receptors.J Hepatol. 2004 May;40(5):792-8. doi: 10.1016/j.jhep.2004.01.016.
12	Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with major depression.Mol Psychiatry. 2012 Nov;17(11):1130-42. doi: 10.1038/mp.2011.113. Epub 2011 Sep 13.
13	Differential Peripheral Proteomic Biosignature of Fluoxetine Response in a Mouse Model of Anxiety/Depression.Front Cell Neurosci. 2017 Aug 16;11:237. doi: 10.3389/fncel.2017.00237. eCollection 2017.
14	The components of somatostatin and ghrelin systems are altered in neuroendocrine lung carcinoids and associated to clinical-histological features.Lung Cancer. 2017 Jul;109:128-136. doi: 10.1016/j.lungcan.2017.05.006. Epub 2017 May 13.
15	NMDA receptor antagonist prevents cell death in the hippocampal dentate gyrus induced by hyponatremia accompanying adrenal insufficiency in rats.Exp Neurol. 2017 Jan;287(Pt 1):65-74. doi: 10.1016/j.expneurol.2016.08.007. Epub 2016 Aug 12.
16	Fine mapping of the human preprocortistatin gene (CORT) to neuroblastoma consensus deletion region 1p36.3-->p36.2, but absence of mutations in primary tumors.Cytogenet Cell Genet. 2000;89(1-2):62-6. doi: 10.1159/000015566.
17	Mediator Kinase Phosphorylation of STAT1 S727 Promotes Growth of Neoplasms With JAK-STAT Activation.EBioMedicine. 2017 Dec;26:112-125. doi: 10.1016/j.ebiom.2017.11.013. Epub 2017 Nov 21.
18	DNA methylation is associated with inhaled corticosteroid response in persistent childhood asthmatics.Clin Exp Allergy. 2019 Sep;49(9):1225-1234. doi: 10.1111/cea.13447. Epub 2019 Aug 15.
19	A Clinically Relevant Closed-Head Model of Single and Repeat Concussive Injury in the Adult Rat Using a Controlled Cortical Impact Device.J Neurotrauma. 2017 Apr 1;34(7):1351-1363. doi: 10.1089/neu.2016.4517. Epub 2016 Dec 2.
20	The role of Cortistatin-14 in the gastrointestinal motility in mice.Pharmacol Rep. 2018 Apr;70(2):355-363. doi: 10.1016/j.pharep.2017.09.004. Epub 2017 Sep 18.
21	Cortistatin inhibits migration and proliferation of human vascular smooth muscle cells and decreases neointimal formation on carotid artery ligation.Circ Res. 2013 May 24;112(11):1444-55. doi: 10.1161/CIRCRESAHA.112.300695. Epub 2013 Apr 17.
22	Developmental outcomes after gestational antidepressant treatment with sertraline and its discontinuation in an animal model of maternal depression.Behav Brain Res. 2019 Jul 2;366:1-12. doi: 10.1016/j.bbr.2019.03.003. Epub 2019 Mar 2.
23	Circulating levels of cortistatin are correlated with metabolic parameters in patients with newly diagnosed type 2 diabetes mellitus.Peptides. 2017 Aug;94:86-90. doi: 10.1016/j.peptides.2017.05.008. Epub 2017 May 17.
24	Cortistatin binds to TNF- receptors and protects against osteoarthritis.EBioMedicine. 2019 Mar;41:556-570. doi: 10.1016/j.ebiom.2019.02.035. Epub 2019 Feb 28.
25	Levels of the potential biomarker p11 in peripheral blood cells distinguish patients with PTSD from those with other major psychiatric disorders.J Psychiatr Res. 2009 Sep;43(13):1078-85. doi: 10.1016/j.jpsychires.2009.03.010. Epub 2009 Apr 19.
26	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
27	Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
28	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.