Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBZ5SE5)

DOT Name Promotilin (MLN)
Gene Name MLN
Related Disease
Advanced cancer ( )
Analgesia ( )
Breast cancer ( )
Breast carcinoma ( )
Coeliac disease ( )
Colorectal carcinoma ( )
Constipation ( )
Crohn disease ( )
Diabetic kidney disease ( )
Gastric ulcer ( )
Gastroparesis ( )
Hallermann-Streiff syndrome ( )
Inflammatory bowel disease ( )
Liver cirrhosis ( )
Liver failure ( )
Neoplasm ( )
Nephropathy ( )
Primary ciliary dyskinesia ( )
Ulcerative colitis ( )
Type-1/2 diabetes ( )
ACTH-independent macronodular adrenal hyperplasia 1 ( )
Colitis ( )
Peptic esophagitis ( )
UniProt ID
MOTI_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1LBJ; 8IBV
Pfam ID
PF04643 ; PF04644
Sequence
MVSRKAVAALLVVHVAAMLASQTEAFVPIFTYGELQRMQEKERNKGQKKSLSVWQRSGEE
GPVDPAEPIREEENEMIKLTAPLEIGMRMNSRQLEKYPATLEGLLSEMLPQHAAK
Function Plays an important role in the regulation of interdigestive gastrointestinal motility and indirectly causes rhythmic contraction of duodenal and colonic smooth muscle.
KEGG Pathway
Neuroactive ligand-receptor interaction (hsa04080 )
Reactome Pathway
G alpha (q) signalling events (R-HSA-416476 )
Peptide ligand-binding receptors (R-HSA-375276 )

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Altered Expression [1]
Analgesia DISK3TVI Strong Biomarker [2]
Breast cancer DIS7DPX1 Strong Biomarker [3]
Breast carcinoma DIS2UE88 Strong Biomarker [3]
Coeliac disease DISIY60C Strong Altered Expression [4]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [1]
Constipation DISRQXWI Strong Altered Expression [5]
Crohn disease DIS2C5Q8 Strong Genetic Variation [6]
Diabetic kidney disease DISJMWEY Strong Biomarker [7]
Gastric ulcer DISBBGVO Strong Biomarker [8]
Gastroparesis DISDW0SR Strong Biomarker [9]
Hallermann-Streiff syndrome DISNT5DL Strong Genetic Variation [10]
Inflammatory bowel disease DISGN23E Strong Biomarker [11]
Liver cirrhosis DIS4G1GX Strong Altered Expression [12]
Liver failure DISLGEL6 Strong Altered Expression [13]
Neoplasm DISZKGEW Strong Biomarker [11]
Nephropathy DISXWP4P Strong Biomarker [7]
Primary ciliary dyskinesia DISOBC7V Strong Genetic Variation [14]
Ulcerative colitis DIS8K27O Strong Biomarker [11]
Type-1/2 diabetes DISIUHAP moderate Biomarker [9]
ACTH-independent macronodular adrenal hyperplasia 1 DISH2YV8 Limited Genetic Variation [15]
Colitis DISAF7DD Limited Biomarker [16]
Peptic esophagitis DISJSGBZ Limited Biomarker [17]
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⏷ Show the Full List of 23 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
Carbamazepine DMZOLBI Approved Promotilin (MLN) affects the response to substance of Carbamazepine. [10]
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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 increases the methylation of Promotilin (MLN). [18]
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2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Triclosan DMZUR4N Approved Triclosan increases the expression of Promotilin (MLN). [19]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Promotilin (MLN). [20]
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References

1 Enterohormonal disturbances in colorectal cancer patients.Neoplasma. 2017;64(3):421-429. doi: 10.4149/neo_2017_313.
2 Effects of hydromorphone and morphine intravenous analgesia on plasma motilin and postoperative nausea and vomiting in patients undergoing total hysterectomy.Eur Rev Med Pharmacol Sci. 2018 Sep;22(17):5697-5703. doi: 10.26355/eurrev_201809_15837.
3 Two distinct amplified regions at 17q11-q21 involved in human primary breast cancer.Cancer Res. 1996 Sep 1;56(17):3886-90.
4 Plasma motilin in untreated celiac disease.Peptides. 2003 Mar;24(3):483-6. doi: 10.1016/s0196-9781(03)00079-2.
5 Protective effect of mulberry (Morus atropurpurea) fruit against diphenoxylate-induced constipation in mice through the modulation of gut microbiota.Food Funct. 2019 Mar 20;10(3):1513-1528. doi: 10.1039/c9fo00132h.
6 Genome-wide association study of Crohn's disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations.Gut. 2014 Jan;63(1):80-7. doi: 10.1136/gutjnl-2013-305193. Epub 2013 Jul 14.
7 Analysis on difference in gastrointestinal hormone levels of patients with the history of diabetes and concurrent nephropathy and study on the role of liraglutide.Eur Rev Med Pharmacol Sci. 2017 Aug;21(15):3523-3529.
8 1-Deoxynojirimycin (DNJ) Ameliorates Indomethacin-Induced Gastric Ulcer in Mice by Affecting NF-kappaB Signaling Pathway.Front Pharmacol. 2018 Apr 19;9:372. doi: 10.3389/fphar.2018.00372. eCollection 2018.
9 Elevated Circulating Levels of Motilin are Associated with Diabetes in Individuals after Acute Pancreatitis.Exp Clin Endocrinol Diabetes. 2020 Jan;128(1):43-51. doi: 10.1055/a-0859-7168. Epub 2019 Mar 14.
10 Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. Pharmacogenet Genomics. 2006 Apr;16(4):297-306. doi: 10.1097/01.fpc.0000199500.46842.4a.
11 Motilin receptor expression in smooth muscle, myenteric plexus, and mucosa of human inflamed and noninflamed intestine.Inflamm Bowel Dis. 2008 May;14(5):612-9. doi: 10.1002/ibd.20364.
12 A correlation between gastrointestinal dysfunction and cirrhosis severity.Medicine (Baltimore). 2018 Sep;97(37):e12070. doi: 10.1097/MD.0000000000012070.
13 STORE-gastrointestinal functions and gastrointestinal hormones in patients with liver failure.Medicine (Baltimore). 2018 Nov;97(48):e13167. doi: 10.1097/MD.0000000000013167.
14 The motilin gene: subregional localisation, tissue expression, DNA polymorphisms and exclusion as a candidate gene for the HLA-associated immotile cilia syndrome.Hum Genet. 1994 Dec;94(6):671-4. doi: 10.1007/BF00206962.
15 Systematic analysis of G protein-coupled receptor gene expression in adrenocorticotropin-independent macronodular adrenocortical hyperplasia identifies novel targets for pharmacological control of adrenal Cushing's syndrome.J Clin Endocrinol Metab. 2010 Oct;95(10):E253-62. doi: 10.1210/jc.2009-2281. Epub 2010 Jul 21.
16 Gut Inflammation in Mice Triggers Proliferation and Function of Mucosal Foxp3+ Regulatory T Cells but Impairs Their Conversion from CD4+ T Cells.J Crohns Colitis. 2017 Jan;11(1):105-117. doi: 10.1093/ecco-jcc/jjw125. Epub 2016 Jun 30.
17 Associations between the severity of reflux esophagitis in children and changes in oxidative stress, serum inflammation, vasoactive intestinal peptide and motilin.Exp Ther Med. 2019 Nov;18(5):3509-3513. doi: 10.3892/etm.2019.7978. Epub 2019 Sep 6.
18 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.
19 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
20 Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
21 Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. Pharmacogenet Genomics. 2006 Apr;16(4):297-306. doi: 10.1097/01.fpc.0000199500.46842.4a.