Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYARA94)

• DOT Name: POU domain, class 3, transcription factor 1 (POU3F1)
• Synonyms: Octamer-binding protein 6; Oct-6; Octamer-binding transcription factor 6; OTF-6; POU domain transcription factor SCIP
• Gene Name: POU3F1
• Related Disease:
  Neural tube defect
  Bipolar disorder
  Hepatocellular carcinoma
  leukaemia
  Leukemia
  Mental disorder
  Mood disorder
  Neoplasm
  Non-small-cell lung cancer
  Peripheral neuropathy
  Schizophrenia
  Lung cancer
  Lung carcinoma
  Non-insulin dependent diabetes
  Rheumatoid arthritis
  Venous thromboembolism
• UniProt ID: PO3F1_HUMAN
• Pfam ID: PF00046 ; PF00157
• Sequence:
  MATTAQYLPRGPGGGAGGTGPLMHPDAAAAAAAAAAAERLHAGAAYREVQKLMHHEWLGA
  GAGHPVGLAHPQWLPTGGGGGGDWAGGPHLEHGKAGGGGTGRADDGGGGGGFHARLVHQG
  AAHAGAAWAQGSTAHHLGPAMSPSPGASGGHQPQPLGLYAQAAYPGGGGGGLAGMLAAGG
  GGAGPGLHHALHEDGHEAQLEPSPPPHLGAHGHAHGHAHAGGLHAAAAHLHPGAGGGGSS
  VGEHSDEDAPSSDDLEQFAKQFKQRRIKLGFTQADVGLALGTLYGNVFSQTTICRFEALQ
  LSFKNMCKLKPLLNKWLEETDSSSGSPTNLDKIAAQGRKRKKRTSIEVGVKGALESHFLK
  CPKPSAHEITGLADSLQLEKEVVRVWFCNRRQKEKRMTPAAGAGHPPMDDVYAPGELGPG
  GGGASPPSAPPPPPPAALHHHHHHTLPGSVQ
• Function: Transcription factor that binds to the octamer motif (5'-ATTTGCAT-3'). Acts as a transcriptional activator when binding cooperatively with SOX4, SOX11, or SOX12 to gene promoters. Acts as a transcriptional repressor of myelin-specific genes.
• Tissue Specificity: Expressed in embryonal stem cells and in the developing brain.
• Reactome Pathway:
  Formation of the anterior neural plate (R-HSA-9823739)
  Formation of the posterior neural plate (R-HSA-9832991)
  EGR2 and SOX10-mediated initiation of Schwann cell myelination (R-HSA-9619665)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neural tube defect	DIS5J95E	Definitive	Genetic Variation	[1]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Posttranslational Modification	[3]
leukaemia	DISS7D1V	Strong	Biomarker	[4]
Leukemia	DISNAKFL	Strong	Biomarker	[4]
Mental disorder	DIS3J5R8	Strong	Biomarker	[2]
Mood disorder	DISLVMWO	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[6]
Peripheral neuropathy	DIS7KN5G	Strong	Biomarker	[7]
Schizophrenia	DISSRV2N	Strong	Biomarker	[8]
Lung cancer	DISCM4YA	moderate	Altered Expression	[9]
Lung carcinoma	DISTR26C	moderate	Altered Expression	[9]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[10]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[11]
Venous thromboembolism	DISUR7CR	Limited	Biomarker	[12]

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 POU domain, class 3, transcription factor 1 (POU3F1).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of POU domain, class 3, transcription factor 1 (POU3F1).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of POU domain, class 3, transcription factor 1 (POU3F1).	[14]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of POU domain, class 3, transcription factor 1 (POU3F1).	[15]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of POU domain, class 3, transcription factor 1 (POU3F1).	[16]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of POU domain, class 3, transcription factor 1 (POU3F1).	[17]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of POU domain, class 3, transcription factor 1 (POU3F1).	[18]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of POU domain, class 3, transcription factor 1 (POU3F1).	[19]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of POU domain, class 3, transcription factor 1 (POU3F1).	[18]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of POU domain, class 3, transcription factor 1 (POU3F1).	[20]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of POU domain, class 3, transcription factor 1 (POU3F1).	[21]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of POU domain, class 3, transcription factor 1 (POU3F1).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of POU domain, class 3, transcription factor 1 (POU3F1).	[23]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of POU domain, class 3, transcription factor 1 (POU3F1).	[24]

References

• [1] Dysregulation of the SIRT1/OCT6 Axis Contributes to Environmental Stress-Induced Neural Induction Defects.Stem Cell Reports. 2017 May 9;8(5):1270-1286. doi: 10.1016/j.stemcr.2017.03.017. Epub 2017 Apr 20.
• [2] Expression of POU-domain transcription factor, Oct-6, in schizophrenia, bipolar disorder and major depression.BMC Psychiatry. 2005 Oct 24;5:38. doi: 10.1186/1471-244X-5-38.
• [3] Aberrant CpG island hypermethylation and down-regulation of Oct-6 mRNA expression in human hepatocellular carcinoma.Dig Dis Sci. 2011 Oct;56(10):3072-7. doi: 10.1007/s10620-011-1686-y. Epub 2011 Mar 30.
• [4] Identification of OCT6 as a novel organic cation transporter preferentially expressed in hematopoietic cells and leukemias. Exp Hematol. 2002 Oct;30(10):1162-9.
• [5] Screening for bipolar disorder among migraineurs: the impact of migraine-bipolar disorder comorbidity on disease characteristics.Neuropsychiatr Dis Treat. 2017 Mar 1;13:631-641. doi: 10.2147/NDT.S121448. eCollection 2017.
• [6] The POU-Domain Transcription Factor Oct-6/POU3F1 as a Regulator of Cellular Response to Genotoxic Stress.Cancers (Basel). 2019 Jun 11;11(6):810. doi: 10.3390/cancers11060810.
• [7] Misexpression of Pou3f1 results in peripheral nerve hypomyelination and axonal loss.J Neurosci. 2007 Oct 24;27(43):11552-9. doi: 10.1523/JNEUROSCI.5497-06.2007.
• [8] Oct-6 transcription factor.Int Rev Neurobiol. 2004;59:471-89. doi: 10.1016/S0074-7742(04)59018-9.
• [9] Organic cation transporter OCT6 mediates cisplatin uptake and resistance to cisplatin in lung cancer.Cancer Chemother Pharmacol. 2015 May;75(5):985-91. doi: 10.1007/s00280-015-2723-x. Epub 2015 Mar 14.
• [10] Discovery of novel 5-oxa-2,6-diazaspiro[3.4]oct-6-ene derivatives as potent, selective, and orally available somatostatin receptor subtype 5 (SSTR5) antagonists for treatment of type 2 diabetes mellitus.Bioorg Med Chem. 2017 Aug 1;25(15):4175-4193. doi: 10.1016/j.bmc.2017.06.007. Epub 2017 Jun 9.
• [11] High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis.Nat Genet. 2012 Dec;44(12):1336-40. doi: 10.1038/ng.2462. Epub 2012 Nov 11.
• [12] Multi-institution Evaluation of Adherence to Comprehensive Postoperative VTE Chemoprophylaxis.Ann Surg. 2020 Jun;271(6):1072-1079. doi: 10.1097/SLA.0000000000003124.
• [13] 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.
• [14] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [15] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [16] 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.
• [17] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [18] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [19] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [20] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [21] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [22] 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.
• [23] 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.
• [24] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.