Details of Drug Off-Target (DOT)

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

DOT Name	Trefoil factor 3 (TFF3)
Synonyms	Intestinal trefoil factor; hITF; Polypeptide P1.B; hP1.B
Gene Name	TFF3
Related Disease	Acute kidney injury ( ) Adenoma ( ) Advanced cancer ( ) Alzheimer disease ( ) B-cell lymphoma ( ) Barrett esophagus ( ) Breast carcinoma ( ) Carcinoma ( ) Carcinoma of esophagus ( ) Colon cancer ( ) Colon carcinoma ( ) Colorectal neoplasm ( ) Depression ( ) Endometrial carcinoma ( ) Endometriosis ( ) Estrogen-receptor positive breast cancer ( ) Fatty liver disease ( ) Gastric cancer ( ) Gastroesophageal reflux disease ( ) Glioma ( ) Hepatocellular carcinoma ( ) Lung adenocarcinoma ( ) Lung cancer ( ) Lung carcinoma ( ) Metastatic malignant neoplasm ( ) Mucositis ( ) Nephropathy ( ) Retinoblastoma ( ) Rheumatoid arthritis ( ) Stomach cancer ( ) Thyroid cancer ( ) Thyroid gland carcinoma ( ) Thyroid gland papillary carcinoma ( ) Thyroid tumor ( ) Type-1/2 diabetes ( ) Non-alcoholic fatty liver disease ( ) Obesity ( ) Pancreatic cancer ( ) Adenocarcinoma ( ) Breast neoplasm ( ) Chronic kidney disease ( ) Colitis ( ) Crohn disease ( ) Fetal growth restriction ( ) Hepatitis C virus infection ( ) Inflammatory bowel disease ( ) Melanoma ( ) Osteoarthritis ( ) Ulcerative colitis ( )
UniProt ID	TFF3_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1E9T; 1PE3; 6V1C
Pfam ID	PF00088
Sequence	MAARALCMLGLVLALLSSSSAEEYVGLSANQCAVPAKDRVDCGYPHVTPKECNNRGCCFD SRIPGVPWCFKPLQEAECTF
Function	Involved in the maintenance and repair of the intestinal mucosa. Promotes the mobility of epithelial cells in healing processes (motogen).
Tissue Specificity	Expressed in goblet cells of the intestines and colon (at protein level). Expressed by goblet cells of small and large intestinal epithelia and also by the uterus. Also expressed in the hypothalamus where it is detected in paraventricular, periventricular and supraoptic nuclei (at protein level).
Reactome Pathway	Estrogen-dependent gene expression (R-HSA-9018519 )

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Acute kidney injury	DISXZG0T	Strong	Biomarker	[1]
Adenoma	DIS78ZEV	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
B-cell lymphoma	DISIH1YQ	Strong	Altered Expression	[5]
Barrett esophagus	DIS416Y7	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[7]
Carcinoma	DISH9F1N	Strong	Biomarker	[8]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[9]
Colon cancer	DISVC52G	Strong	Altered Expression	[3]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[3]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[10]
Depression	DIS3XJ69	Strong	Biomarker	[4]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[11]
Endometriosis	DISX1AG8	Strong	Altered Expression	[12]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Biomarker	[13]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[14]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[15]
Gastroesophageal reflux disease	DISQ8G5S	Strong	Biomarker	[16]
Glioma	DIS5RPEH	Strong	Biomarker	[17]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[18]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[19]
Lung cancer	DISCM4YA	Strong	Altered Expression	[20]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[20]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[21]
Mucositis	DIS3FXDI	Strong	Therapeutic	[22]
Nephropathy	DISXWP4P	Strong	Biomarker	[23]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[24]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[25]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[15]
Thyroid cancer	DIS3VLDH	Strong	Altered Expression	[26]
Thyroid gland carcinoma	DISMNGZ0	Strong	Altered Expression	[26]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Biomarker	[27]
Thyroid tumor	DISLVKMD	Strong	Altered Expression	[26]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[14]
Non-alcoholic fatty liver disease	DISDG1NL	moderate	Biomarker	[14]
Obesity	DIS47Y1K	moderate	Altered Expression	[14]
Pancreatic cancer	DISJC981	moderate	Altered Expression	[28]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[29]
Breast neoplasm	DISNGJLM	Limited	Altered Expression	[30]
Chronic kidney disease	DISW82R7	Limited	Biomarker	[31]
Colitis	DISAF7DD	Limited	Altered Expression	[32]
Crohn disease	DIS2C5Q8	Limited	Altered Expression	[33]
Fetal growth restriction	DIS5WEJ5	Limited	Biomarker	[34]
Hepatitis C virus infection	DISQ0M8R	Limited	Altered Expression	[35]
Inflammatory bowel disease	DISGN23E	Limited	Biomarker	[33]
Melanoma	DIS1RRCY	Limited	Biomarker	[36]
Osteoarthritis	DIS05URM	Limited	Altered Expression	[25]
Ulcerative colitis	DIS8K27O	Limited	Altered Expression	[33]
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⏷ Show the Full List of 49 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Trefoil factor 3 (TFF3) affects the response to substance of Etoposide.	[49]
Mitomycin	DMH0ZJE	Approved	Trefoil factor 3 (TFF3) affects the response to substance of Mitomycin.	[49]
Mitoxantrone	DMM39BF	Approved	Trefoil factor 3 (TFF3) affects the response to substance of Mitoxantrone.	[49]
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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 3 (TFF3).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Trefoil factor 3 (TFF3).	[48]
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14 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Trefoil factor 3 (TFF3).	[38]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Trefoil factor 3 (TFF3).	[39]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Trefoil factor 3 (TFF3).	[40]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Trefoil factor 3 (TFF3).	[41]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Trefoil factor 3 (TFF3).	[41]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Trefoil factor 3 (TFF3).	[39]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Trefoil factor 3 (TFF3).	[42]
Gamolenic acid	DMQN30Z	Approved	Gamolenic acid decreases the expression of Trefoil factor 3 (TFF3).	[43]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Trefoil factor 3 (TFF3).	[44]
Fenretinide	DMRD5SP	Phase 3	Fenretinide decreases the expression of Trefoil factor 3 (TFF3).	[45]
Coprexa	DMA0WEK	Phase 3	Coprexa decreases the expression of Trefoil factor 3 (TFF3).	[46]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Trefoil factor 3 (TFF3).	[47]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Trefoil factor 3 (TFF3).	[47]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Trefoil factor 3 (TFF3).	[44]
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⏷ Show the Full List of 14 Drug(s)

References

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11	Hypomethylation associated enhanced transcription of trefoil factor-3 mediates tamoxifen-stimulated oncogenicity of ER+ endometrial carcinoma cells.Oncotarget. 2017 Aug 24;8(44):77268-77291. doi: 10.18632/oncotarget.20461. eCollection 2017 Sep 29.
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18	The predictive powers of plasma trefoil factor 3 or its related micro RNAs for patients with hepatocellular carcinoma.BMC Cancer. 2018 Nov 13;18(1):1110. doi: 10.1186/s12885-018-5017-y.
19	A novel small-molecule inhibitor of trefoil factor 3 (TFF3) potentiates MEK1/2 inhibition in lung adenocarcinoma.Oncogenesis. 2019 Nov 4;8(11):65. doi: 10.1038/s41389-019-0173-8.
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22	Phase II, randomized, double-blind, placebo-controlled study of recombinant human intestinal trefoil factor oral spray for prevention of oral mucositis in patients with colorectal cancer who are receiving fluorouracil-based chemotherapy.J Clin Oncol. 2009 Sep 10;27(26):4333-8. doi: 10.1200/JCO.2008.21.2381. Epub 2009 Jul 27.
23	Identification of urinary miRNA biomarkers for detecting cisplatin-induced proximal tubular injury in rats.Toxicology. 2014 Oct 3;324:158-68. doi: 10.1016/j.tox.2014.05.004. Epub 2014 May 24.
24	p53, miR-34a and EMP1-Newly Identified Targets of TFF3 Signaling in Y79 Retinoblastoma Cells.Int J Mol Sci. 2019 Aug 24;20(17):4129. doi: 10.3390/ijms20174129.
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.
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33	Serum trefoil factor 3 predicts disease activity in patients with ulcerative colitis.Eur Rev Med Pharmacol Sci. 2019 Jan;23(2):788-794. doi: 10.26355/eurrev_201901_16893.
34	Intrauterine growth restriction alters postnatal colonic barrier maturation in rats.Pediatr Res. 2009 Jul;66(1):47-52. doi: 10.1203/PDR.0b013e3181a2047e.
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