Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV20NGX)

DOT Name	Forkhead box protein F2 (FOXF2)
Synonyms	Forkhead-related activator 2; FREAC-2; Forkhead-related protein FKHL6; Forkhead-related transcription factor 2
Gene Name	FOXF2
Related Disease	Advanced cancer ( ) Benign prostatic hyperplasia ( ) Breast neoplasm ( ) Bronchopulmonary dysplasia ( ) Cerebral infarction ( ) Cervical cancer ( ) Cervical carcinoma ( ) Colorectal carcinoma ( ) Disorder of sexual differentiation ( ) Esophageal squamous cell carcinoma ( ) Hepatocellular carcinoma ( ) HER2/NEU overexpressing breast cancer ( ) Neoplasm ( ) Non-small-cell lung cancer ( ) Prostate cancer ( ) Prostate carcinoma ( ) Stroke ( ) Gastroparesis ( ) Metastatic malignant neoplasm ( ) Rhabdomyosarcoma ( ) Sensorineural hearing loss disorder ( ) Breast cancer ( ) Breast carcinoma ( ) Cleft palate ( ) Gastric cancer ( ) Isolated cleft palate ( ) Stomach cancer ( )
UniProt ID	FOXF2_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF00250
Sequence	MTTEGGPPPAPLRRACSPVPGALQAALMSPPPAAAAAAAAAPETTSSSSSSSSASCASSS SSSNSASAPSAACKSAGGGGAGAGSGGAKKASSGLRRPEKPPYSYIALIVMAIQSSPSKR LTLSEIYQFLQARFPFFRGAYQGWKNSVRHNLSLNECFIKLPKGLGRPGKGHYWTIDPAS EFMFEEGSFRRRPRGFRRKCQALKPMYHRVVSGLGFGASLLPQGFDFQAPPSAPLGCHSQ GGYGGLDMMPAGYDAGAGAPSHAHPHHHHHHHVPHMSPNPGSTYMASCPVPAGPGGVGAA GGGGGGDYGPDSSSSPVPSSPAMASAIECHSPYTSPAAHWSSPGASPYLKQPPALTPSSN PAASAGLHSSMSSYSLEQSYLHQNAREDLSVGLPRYQHHSTPVCDRKDFVLNFNGISSFH PSASGSYYHHHHQSVCQDIKPCVM
Function	Probable transcription activator for a number of lung-specific genes. Mediates up-regulation of the E3 ligase IRF2BPL and drives ubiquitination and degradation of CTNNB1.
Tissue Specificity	Lung and placenta . Predominantly expressed in gastrointestinal tract including stomach .

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[2]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[3]
Bronchopulmonary dysplasia	DISO0BY5	Strong	Altered Expression	[4]
Cerebral infarction	DISR1WNP	Strong	Biomarker	[5]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[6]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Disorder of sexual differentiation	DISRMAEZ	Strong	Genetic Variation	[8]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[10]
HER2/NEU overexpressing breast cancer	DISYKID5	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[11]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[12]
Prostate cancer	DISF190Y	Strong	Altered Expression	[2]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[2]
Stroke	DISX6UHX	Strong	Biomarker	[13]
Gastroparesis	DISDW0SR	moderate	Altered Expression	[14]
Metastatic malignant neoplasm	DIS86UK6	moderate	Altered Expression	[15]
Rhabdomyosarcoma	DISNR7MS	moderate	Altered Expression	[16]
Sensorineural hearing loss disorder	DISJV45Z	moderate	Biomarker	[17]
Breast cancer	DIS7DPX1	Limited	Biomarker	[18]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[18]
Cleft palate	DIS6G5TF	Limited	Biomarker	[19]
Gastric cancer	DISXGOUK	Limited	Biomarker	[11]
Isolated cleft palate	DISV80CD	Limited	Biomarker	[19]
Stomach cancer	DISKIJSX	Limited	Biomarker	[11]
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⏷ Show the Full List of 27 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Forkhead box protein F2 (FOXF2) affects the response to substance of Temozolomide.	[29]
Etoposide	DMNH3PG	Approved	Forkhead box protein F2 (FOXF2) affects the response to substance of Etoposide.	[30]
DTI-015	DMXZRW0	Approved	Forkhead box protein F2 (FOXF2) affects the response to substance of DTI-015.	[29]
Mitoxantrone	DMM39BF	Approved	Forkhead box protein F2 (FOXF2) affects the response to substance of Mitoxantrone.	[30]
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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 Forkhead box protein F2 (FOXF2).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Forkhead box protein F2 (FOXF2).	[27]
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8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Forkhead box protein F2 (FOXF2).	[21]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Forkhead box protein F2 (FOXF2).	[22]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Forkhead box protein F2 (FOXF2).	[23]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Forkhead box protein F2 (FOXF2).	[24]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Forkhead box protein F2 (FOXF2).	[25]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Forkhead box protein F2 (FOXF2).	[26]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Forkhead box protein F2 (FOXF2).	[25]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Forkhead box protein F2 (FOXF2).	[28]
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⏷ Show the Full List of 8 Drug(s)

References

1	Reciprocal transrepression between FOXF2 and FOXQ1 controls basal-like breast cancer aggressiveness.FASEB J. 2019 May;33(5):6564-6573. doi: 10.1096/fj.201801916R. Epub 2019 Feb 26.
2	Gene expression of forkhead transcription factors in the normal and diseased human prostate.BJU Int. 2009 Jun;103(11):1574-80. doi: 10.1111/j.1464-410X.2009.08351.x. Epub 2009 Feb 11.
3	The dual role of FOXF2 in regulation of DNA replication and the epithelial-mesenchymal transition in breast cancer progression.Cell Signal. 2016 Oct;28(10):1502-19. doi: 10.1016/j.cellsig.2016.06.021. Epub 2016 Jul 1.
4	Gene Expression Signatures Point to a Male Sex-Specific Lung Mesenchymal Cell PDGF Receptor Signaling Defect in Infants Developing Bronchopulmonary Dysplasia.Sci Rep. 2018 Nov 20;8(1):17070. doi: 10.1038/s41598-018-35256-z.
5	Identification of additional risk loci for stroke and small vessel disease: a meta-analysis of genome-wide association studies.Lancet Neurol. 2016 Jun;15(7):695-707. doi: 10.1016/S1474-4422(16)00102-2. Epub 2016 Apr 7.
6	FOXF2 inhibits proliferation, migration, and invasion of Hela cells by regulating Wnt signaling pathway.Biosci Rep. 2018 Oct 17;38(5):BSR20180747. doi: 10.1042/BSR20180747. Print 2018 Oct 31.
7	MicroRNA-130a is upregulated in colorectal cancer and promotes cell growth and motility by directly targeting forkhead box F2.Mol Med Rep. 2017 Oct;16(4):5241-5248. doi: 10.3892/mmr.2017.7257. Epub 2017 Aug 16.
8	Mutation analysis of FOXF2 in patients with disorders of sex development (DSD) in combination with cleft palate.Sex Dev. 2008;2(6):302-8. doi: 10.1159/000195679. Epub 2009 Mar 10.
9	FOXF2 promoter methylation is associated with prognosis in esophageal squamous cell carcinoma.Tumour Biol. 2017 Feb;39(2):1010428317692230. doi: 10.1177/1010428317692230.
10	FOXF2 deficiency promotes hepatocellular carcinoma metastasis by inducing mesenchymal-epithelial transition.Cancer Biomark. 2017 Jul 4;19(4):447-454. doi: 10.3233/CBM-170139.
11	Forkhead Box F2 Suppresses Gastric Cancer through a Novel FOXF2-IRF2BPL--Catenin Signaling Axis.Cancer Res. 2018 Apr 1;78(7):1643-1656. doi: 10.1158/0008-5472.CAN-17-2403. Epub 2018 Jan 26.
12	Polymorphisms in Epithelial-Mesenchymal Transition-Related Genes and the Prognosis of Surgically Treated Non-small Cell Lung Cancer.Ann Surg Oncol. 2017 Oct;24(11):3386-3395. doi: 10.1245/s10434-017-6002-4. Epub 2017 Aug 1.
13	Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.Nat Genet. 2018 Apr;50(4):524-537. doi: 10.1038/s41588-018-0058-3. Epub 2018 Mar 12.
14	Gastroparesis is associated with decreased FOXF1 and FOXF2 in humans, and loss of FOXF1 and FOXF2 results in gastroparesis in mice.Neurogastroenterol Motil. 2019 Mar;31(3):e13528. doi: 10.1111/nmo.13528. Epub 2018 Dec 19.
15	MiR-200c inhibits metastasis of breast tumor via the downregulation of Foxf2.Genet Mol Res. 2017 Aug 17;16(3). doi: 10.4238/gmr16038971.
16	FoxF1 and FoxF2 transcription factors synergistically promote rhabdomyosarcoma carcinogenesis by repressing transcription of p21(Cip1) CDK inhibitor.Oncogene. 2017 Feb 9;36(6):850-862. doi: 10.1038/onc.2016.254. Epub 2016 Jul 18.
17	FOXF2 is required for cochlear development in humans and mice.Hum Mol Genet. 2019 Apr 15;28(8):1286-1297. doi: 10.1093/hmg/ddy431.
18	FOXF2 reprograms breast cancer cells into bone metastasis seeds.Nat Commun. 2019 Jun 20;10(1):2707. doi: 10.1038/s41467-019-10379-7.
19	A Shh-Foxf-Fgf18-Shh Molecular Circuit Regulating Palate Development.PLoS Genet. 2016 Jan 8;12(1):e1005769. doi: 10.1371/journal.pgen.1005769. eCollection 2016 Jan.
20	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.
21	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
22	Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
23	Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
24	Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
25	Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
26	Gene expression profiling identifies activating transcription factor 3 as a novel contributor to the proapoptotic effect of curcumin. Mol Cancer Ther. 2005 Feb;4(2):233-41.
27	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.
28	Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
29	Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006 Jan 10;24(2):274-87. doi: 10.1200/JCO.2005.02.9405. Epub 2005 Dec 19.
30	Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.