Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAF63YV)

• DOT Name: Forkhead box protein D2 (FOXD2)
• Synonyms: Forkhead-related protein FKHL17; Forkhead-related transcription factor 9; FREAC-9
• Gene Name: FOXD2
• Related Disease:
  Advanced cancer
  Esophageal squamous cell carcinoma
  Glioma
  Neoplasm
  Non-small-cell lung cancer
  Prostate cancer
  Prostate carcinoma
• UniProt ID: FOXD2_HUMAN
• Pfam ID: PF00250
• Sequence:
  MTLGSCCCEIMSSESSPAALSEADADIDVVGGGSGGGELPARSGPRAPRDVLPHGHEPPA
  EEAEADLAEDEEESGGCSDGEPRALASRGAAAAAGSPGPGAAAARGAAGPGPGPPSGGAA
  TRSPLVKPPYSYIALITMAILQSPKKRLTLSEICEFISGRFPYYREKFPAWQNSIRHNLS
  LNDCFVKIPREPGNPGKGNYWTLDPESADMFDNGSFLRRRKRFKRQPLPPPHPHPHPHPE
  LLLRGGAAAAGDPGAFLPGFAAYGAYGYGYGLALPAYGAPPPGPAPHPHPHPHAFAFAAA
  AAAAPCQLSVPPGRAAAPPPGPPTASVFAGAGSAPAPAPASGSGPGPGPAGLPAFLGAEL
  GCAKAFYAASLSPPAAGTAAGLPTALLRQGLKTDAGGGAGGGGAGAGQRPSFSIDHIMGH
  GGGGAAPPGAGEGSPGPPFAAAAGPGGQAQVLAMLTAPALAPVAGHIRLSHPGDALLSSG
  SRFASKVAGLSGCHF
• Function: Probable transcription factor involved in embryogenesis and somatogenesis.
• Tissue Specificity: Kidney specific.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[2]
Glioma	DIS5RPEH	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[5]
Prostate cancer	DISF190Y	Strong	Altered Expression	[6]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[6]

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 D2 (FOXD2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Forkhead box protein D2 (FOXD2).	[12]

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 decreases the expression of Forkhead box protein D2 (FOXD2).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Forkhead box protein D2 (FOXD2).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Forkhead box protein D2 (FOXD2).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Forkhead box protein D2 (FOXD2).	[11]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Forkhead box protein D2 (FOXD2).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Forkhead box protein D2 (FOXD2).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Forkhead box protein D2 (FOXD2).	[13]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Forkhead box protein D2 (FOXD2).	[14]

References

• [1] Downregulation of the long noncoding RNA FOXD2AS1 inhibits cell proliferation, migration and invasion in osteosarcoma.Mol Med Rep. 2019 Jul;20(1):292-302. doi: 10.3892/mmr.2019.10254. Epub 2019 May 16.
• [2] Overexpression of the Long Noncoding RNA FOXD2-AS1 Promotes Cisplatin Resistance in Esophageal Squamous Cell Carcinoma Through the miR-195/Akt/mTOR Axis.Oncol Res. 2020 Feb 7;28(1):65-73. doi: 10.3727/096504019X15656904013079. Epub 2019 Sep 26.
• [3] FoxD2-AS1 is a prognostic factor in glioma and promotes temozolomide resistance in a O(6)-methylguanine-DNA methyltransferase-dependent manner.Korean J Physiol Pharmacol. 2019 Nov;23(6):475-482. doi: 10.4196/kjpp.2019.23.6.475. Epub 2019 Oct 24.
• [4] Long noncoding RNA FOXD2AS1/miR?50?p/PFN2 axis regulates breast cancer malignancy and tumorigenesis.Int J Oncol. 2019 Mar;54(3):1043-1052. doi: 10.3892/ijo.2019.4671. Epub 2019 Jan 3.
• [5] lncRNA FOXD2-AS1 confers cisplatin resistance of non-small-cell lung cancer via regulation of miR185-5p-SIX1 axis.Onco Targets Ther. 2019 Jul 30;12:6105-6117. doi: 10.2147/OTT.S197454. eCollection 2019.
• [6] 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.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [10] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [11] 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.
• [12] 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.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.