Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6S3EB0)

• DOT Name: Forkhead box protein Q1 (FOXQ1)
• Synonyms: HNF-3/forkhead-like protein 1; HFH-1; Hepatocyte nuclear factor 3 forkhead homolog 1
• Gene Name: FOXQ1
• UniProt ID: FOXQ1_HUMAN
• Pfam ID: PF00250
• Sequence:
  MKLEVFVPRAAHGDKQGSDLEGAGGSDAPSPLSAAGDDSLGSDGDCAANSPAAGGGARDT
  QGDGEQSAGGGPGAEEAIPAAAAAAVVAEGAEAGAAGPGAGGAGSGEGARSKPYTRRPKP
  PYSYIALIAMAIRDSAGGRLTLAEINEYLMGKFPFFRGSYTGWRNSVRHNLSLNDCFVKV
  LRDPSRPWGKDNYWMLNPNSEYTFADGVFRRRRKRLSHRAPVPAPGLRPEEAPGLPAAPP
  PAPAAPASPRMRSPARQEERASPAGKFSSSFAIDSILRKPFRSRRLRDTAPGTTLQWGAA
  PCPPLPAFPALLPAAPCRALLPLCAYGAGEPARLGAREAEVPPTAPPLLLAPLPAAAPAK
  PLRGPAAGGAHLYCPLRLPAALQAASVRRPGPHLPYPVETLLA
• Function: Plays a role in hair follicle differentiation.
• Tissue Specificity: Expressed predominantly in the stomach, trachea, bladder and salivary gland.

Molecular Interaction Atlas (MIA) of This DOT

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 Forkhead box protein Q1 (FOXQ1).	[1]

16 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Forkhead box protein Q1 (FOXQ1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Forkhead box protein Q1 (FOXQ1).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Forkhead box protein Q1 (FOXQ1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Forkhead box protein Q1 (FOXQ1).	[2]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Forkhead box protein Q1 (FOXQ1).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Forkhead box protein Q1 (FOXQ1).	[6]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Forkhead box protein Q1 (FOXQ1).	[7]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Forkhead box protein Q1 (FOXQ1).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Forkhead box protein Q1 (FOXQ1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Forkhead box protein Q1 (FOXQ1).	[2]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Forkhead box protein Q1 (FOXQ1).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Forkhead box protein Q1 (FOXQ1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Forkhead box protein Q1 (FOXQ1).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Forkhead box protein Q1 (FOXQ1).	[13]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Forkhead box protein Q1 (FOXQ1).	[14]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Forkhead box protein Q1 (FOXQ1).	[15]

References

• [1] 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.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [6] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [7] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [8] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [13] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [14] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [15] In vitro effects of aldehydes present in tobacco smoke on gene expression in human lung alveolar epithelial cells. Toxicol In Vitro. 2013 Apr;27(3):1072-81.