Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRXB19X)

DOT Name Trefoil factor 2 (TFF2)
Synonyms Spasmolysin; Spasmolytic polypeptide; SP
Gene Name TFF2
Related Disease
Adenocarcinoma ( )
Advanced cancer ( )
Allergic asthma ( )
Bacteremia ( )
Barrett esophagus ( )
Breast neoplasm ( )
Carcinoma of esophagus ( )
Cholangiocarcinoma ( )
Chronic kidney disease ( )
Colitis ( )
Colon cancer ( )
Colon carcinoma ( )
Colonic neoplasm ( )
Colorectal carcinoma ( )
Congenital contractural arachnodactyly ( )
Crohn disease ( )
Gastritis ( )
Gastroesophageal reflux disease ( )
Hereditary diffuse gastric adenocarcinoma ( )
Inflammatory bowel disease ( )
Intestinal neoplasm ( )
Lung cancer ( )
Lung carcinoma ( )
Obesity ( )
Polyp ( )
Precancerous condition ( )
Pulmonary disease ( )
Retinoblastoma ( )
Ulcerative colitis ( )
Breast cancer ( )
Breast carcinoma ( )
Gastric neoplasm ( )
Pancreatic cancer ( )
Gastric ulcer ( )
Asthma ( )
Chronic pancreatitis ( )
Osteoarthritis ( )
Rheumatoid arthritis ( )
Streptococcal pneumonia ( )
UniProt ID
TFF2_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00088
Sequence
MGRRDAQLLAALLVLGLCALAGSEKPSPCQCSRLSPHNRTNCGFPGITSDQCFDNGCCFD
SSVTGVPWCFHPLPKQESDQCVMEVSDRRNCGYPGISPEECASRKCCFSNFIFEVPWCFF
PKSVEDCHY
Function
Inhibits gastrointestinal motility and gastric acid secretion. Could function as a structural component of gastric mucus, possibly by stabilizing glycoproteins in the mucus gel through interactions with carbohydrate side chains.
Tissue Specificity Stomach.

Molecular Interaction Atlas (MIA) of This DOT

39 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adenocarcinoma DIS3IHTY Strong Altered Expression [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Allergic asthma DISHF0H3 Strong Biomarker [3]
Bacteremia DIS6N9RZ Strong Biomarker [4]
Barrett esophagus DIS416Y7 Strong Biomarker [5]
Breast neoplasm DISNGJLM Strong Altered Expression [6]
Carcinoma of esophagus DISS6G4D Strong Altered Expression [7]
Cholangiocarcinoma DIS71F6X Strong Genetic Variation [8]
Chronic kidney disease DISW82R7 Strong Altered Expression [9]
Colitis DISAF7DD Strong Biomarker [2]
Colon cancer DISVC52G Strong Genetic Variation [10]
Colon carcinoma DISJYKUO Strong Genetic Variation [10]
Colonic neoplasm DISSZ04P Strong Biomarker [2]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [2]
Congenital contractural arachnodactyly DISOM1K7 Strong Biomarker [8]
Crohn disease DIS2C5Q8 Strong Biomarker [11]
Gastritis DIS8G07K Strong Altered Expression [12]
Gastroesophageal reflux disease DISQ8G5S Strong Biomarker [5]
Hereditary diffuse gastric adenocarcinoma DISUIBYS Strong Altered Expression [13]
Inflammatory bowel disease DISGN23E Strong Biomarker [14]
Intestinal neoplasm DISK0GUH Strong Biomarker [15]
Lung cancer DISCM4YA Strong Altered Expression [16]
Lung carcinoma DISTR26C Strong Altered Expression [16]
Obesity DIS47Y1K Strong Biomarker [17]
Polyp DISRSLYF Strong Biomarker [18]
Precancerous condition DISV06FL Strong Altered Expression [19]
Pulmonary disease DIS6060I Strong Biomarker [3]
Retinoblastoma DISVPNPB Strong Altered Expression [20]
Ulcerative colitis DIS8K27O Strong Biomarker [11]
Breast cancer DIS7DPX1 moderate Biomarker [21]
Breast carcinoma DIS2UE88 moderate Biomarker [21]
Gastric neoplasm DISOKN4Y moderate Posttranslational Modification [22]
Pancreatic cancer DISJC981 moderate Altered Expression [23]
Gastric ulcer DISBBGVO Disputed Altered Expression [19]
Asthma DISW9QNS Limited Genetic Variation [24]
Chronic pancreatitis DISBUOMJ Limited Biomarker [23]
Osteoarthritis DIS05URM Limited Altered Expression [25]
Rheumatoid arthritis DISTSB4J Limited Altered Expression [25]
Streptococcal pneumonia DIS2EKMJ Limited Biomarker [26]
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⏷ Show the Full List of 39 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 Trefoil factor 2 (TFF2). [27]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Trefoil factor 2 (TFF2). [32]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Estradiol DMUNTE3 Approved Estradiol increases the expression of Trefoil factor 2 (TFF2). [28]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Trefoil factor 2 (TFF2). [29]
Fulvestrant DM0YZC6 Approved Fulvestrant decreases the expression of Trefoil factor 2 (TFF2). [28]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of Trefoil factor 2 (TFF2). [30]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Trefoil factor 2 (TFF2). [31]
Belinostat DM6OC53 Phase 2 Belinostat decreases the expression of Trefoil factor 2 (TFF2). [31]
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⏷ Show the Full List of 6 Drug(s)

References

1 Trefoil factor family 2 protein: a potential immunohistochemical marker for aiding diagnosis of lobular endocervical glandular hyperplasia and gastric-type adenocarcinoma of the uterine cervix.Virchows Arch. 2019 Jan;474(1):79-86. doi: 10.1007/s00428-018-2469-z. Epub 2018 Oct 15.
2 Therapeutic potential of adenovirus-mediated TFF2-CTP-Flag peptide for treatment of colorectal cancer.Cancer Gene Ther. 2019 Feb;26(1-2):48-57. doi: 10.1038/s41417-018-0036-z. Epub 2018 Jul 25.
3 Trefoil factor 2 rapidly induces interleukin 33 to promote type 2 immunity during allergic asthma and hookworm infection.J Exp Med. 2012 Mar 12;209(3):607-22. doi: 10.1084/jem.20110079. Epub 2012 Feb 13.
4 Loss of Trefoil Factor 2 Sensitizes Rat Pups to Systemic Infection with the Neonatal Pathogen Escherichia coli K1.Infect Immun. 2019 Apr 23;87(5):e00878-18. doi: 10.1128/IAI.00878-18. Print 2019 Mar.
5 Possible application of trefoil factor family peptides in gastroesophageal reflux and Barrett's esophagus.Peptides. 2019 May;115:27-31. doi: 10.1016/j.peptides.2019.02.007. Epub 2019 Mar 1.
6 Expression and motogenic activity of TFF2 in human breast cancer cells.Peptides. 2004 May;25(5):865-72. doi: 10.1016/j.peptides.2003.12.024.
7 Differential expression of mucins and trefoil peptides in native epithelium, Barrett's metaplasia and squamous cell carcinoma of the oesophagus.J Cancer Res Clin Oncol. 1999;125(2):71-6. doi: 10.1007/s004320050244.
8 A novel TFF2 splice variant (EX2TFF2) correlates with longer overall survival time in cholangiocarcinoma.Oncol Rep. 2012 Apr;27(4):1207-12. doi: 10.3892/or.2011.1583. Epub 2011 Dec 7.
9 Increased trefoil factor 2 levels in patients with chronic kidney disease.PLoS One. 2017 Mar 29;12(3):e0174551. doi: 10.1371/journal.pone.0174551. eCollection 2017.
10 TFF2-CXCR4 Axis Is Associated with BRAF V600E Colon Cancer.Cancer Prev Res (Phila). 2015 Jul;8(7):614-9. doi: 10.1158/1940-6207.CAPR-14-0444. Epub 2015 Apr 21.
11 A variant form of the human deleted in malignant brain tumor 1 (DMBT1) gene shows increased expression in inflammatory bowel diseases and interacts with dimeric trefoil factor 3 (TFF3).PLoS One. 2013 May 15;8(5):e64441. doi: 10.1371/journal.pone.0064441. Print 2013.
12 Trefoil factor family 2 expression inhibits gastric cancer cell growth and invasion invitro via interactions with the transcription factor Sp3.Int J Mol Med. 2016 Nov;38(5):1474-1480. doi: 10.3892/ijmm.2016.2739. Epub 2016 Sep 19.
13 Spasmolytic polypeptide-expressing metaplasia associated with higher expressions of miR-21, 155, and 223 can be regressed by Helicobacter pylori eradication in the gastric cancer familial relatives.Helicobacter. 2019 Jun;24(3):e12578. doi: 10.1111/hel.12578. Epub 2019 Apr 16.
14 Immunoassays of human trefoil factors 1 and 2: measured on serum from patients with inflammatory bowel disease.Scand J Clin Lab Invest. 2004 Apr;64(2):146-56. doi: 10.1080/00365510410001176.
15 Involvement of trefoil factor family 2 in the enlargement of intestinal tumors in Apc(Min/+) mice.Biochem Biophys Res Commun. 2015 Aug 7;463(4):859-63. doi: 10.1016/j.bbrc.2015.06.025. Epub 2015 Jun 6.
16 Increased trefoil factor 3 levels in the serum of patients with three major histological subtypes of lung cancer.Oncol Rep. 2012 Apr;27(4):1277-83. doi: 10.3892/or.2012.1627. Epub 2012 Jan 11.
17 Energy and metabolic pathways in trefoil factor family member 2 (Tff2) KO mice beyond the protection from high-fat diet-induced obesity.Life Sci. 2018 Dec 15;215:190-197. doi: 10.1016/j.lfs.2018.11.006. Epub 2018 Nov 7.
18 Hyperplastic polyps: a cell lineage which both synthesizes and secretes trefoil-peptides and has phenotypic similarity with the ulcer-associated cell lineage.Am J Pathol. 1993 Mar;142(3):663-8.
19 Expression of trefoil factors 1 and 2 in precancerous condition and gastric cancer.World J Gastroenterol. 2006 May 21;12(19):3119-22. doi: 10.3748/wjg.v12.i19.3119.
20 Epigenetic control of trefoil factor family (TFF) peptide expression in human retinoblastoma cell lines.Cell Physiol Biochem. 2014;34(3):1001-14. doi: 10.1159/000366316. Epub 2014 Aug 29.
21 Serum TFF1 and TFF3 but not TFF2 are higher in women with breast cancer than in women without breast cancer.Sci Rep. 2017 Jul 7;7(1):4846. doi: 10.1038/s41598-017-05129-y.
22 Helicobacter pylori infection promotes methylation and silencing of trefoil factor 2, leading to gastric tumor development in mice and humans.Gastroenterology. 2010 Dec;139(6):2005-17. doi: 10.1053/j.gastro.2010.08.043. Epub 2010 Aug 27.
23 Trefoil factor(s) and CA19.9: A promising panel for early detection of pancreatic cancer.EBioMedicine. 2019 Apr;42:375-385. doi: 10.1016/j.ebiom.2019.03.056. Epub 2019 Apr 5.
24 Serum perfluoroalkyl substances (PFAS) and risk of asthma and various allergies in adolescents. The Troms study Fit Futures in Northern Norway.Environ Res. 2019 Feb;169:114-121. doi: 10.1016/j.envres.2018.11.005. Epub 2018 Nov 5.
25 Human Synovia Contains Trefoil Factor Family (TFF) Peptides 1-3 Although Synovial Membrane Only Produces TFF3: Implications in Osteoarthritis and Rheumatoid Arthritis.Int J Mol Sci. 2019 Dec 3;20(23):6105. doi: 10.3390/ijms20236105.
26 ASC and NLRP3 maintain innate immune homeostasis in the airway through an inflammasome-independent mechanism.Mucosal Immunol. 2019 Sep;12(5):1092-1103. doi: 10.1038/s41385-019-0181-1. Epub 2019 Jul 5.
27 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.
28 Mechanisms of estrogen receptor antagonism toward p53 and its implications in breast cancer therapeutic response and stem cell regulation. Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15081-6. doi: 10.1073/pnas.1009575107. Epub 2010 Aug 9.
29 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
30 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.
31 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.
32 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.