Details of Drug Off-Target (DOT)

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

• DOT Name: Protein PHTF2 (PHTF2)
• Gene Name: PHTF2
• UniProt ID: PHTF2_HUMAN
• Pfam ID: PF12129
• Sequence:
  MASKVTDAIVWYQKKEFLSVATTAPGPQQVLPGYCQCSLKDQGLFIQCLIGAYDQQIWEK
  SVEQREIKFIKLGLRNKPKKTAHVKPDLIDVDLVRGSAFAKAKPESPWTSLTRKGIVRVV
  FFPFFFRWWLQVTSKVIFFWLLVLYLLQVAAIVLFCSTSSPHSIPLTEVIGPIWLMLLLG
  TVHCQIVSTRTPKPPLSTGGKRRRKLRKAAHLEVHREGDGSSTTDNTQEGAVQNHGTSTS
  HSVGTVFRDLWHAAFFLSGSKKAKNSIDKSTETDNGYVSLDGKKTVKSGEDGIQNHEPQC
  ETIRPEETAWNTGTLRNGPSKDTQRTITNVSDEVSSEEGPETGYSLRRHVDRTSEGVLRN
  RKSHHYKKHYPNEDAPKSGTSCSSRCSSSRQDSESARPESETEDVLWEDLLHCAECHSSC
  TSETDVENHQINPCVKKEYRDDPFHQSHLPWLHSSHPGLEKISAIVWEGNDCKKADMSVL
  EISGMIMNRVNSHIPGIGYQIFGNAVSLILGLTPFVFRLSQATDLEQLTAHSASELYVIA
  FGSNEDVIVLSMVIISFVVRVSLVWIFFFLLCVAERTYKQRLLFAKLFGHLTSARRARKS
  EVPHFRLKKVQNIKMWLSLRSYLKRRGPQRSVDVIVSSAFLLTISVVFICCAQLLHVHEI
  FLDCHYNWELVIWCISLTLFLLRFVTLGSETSKKYSNTSILLTEQINLYLKMEKKPNKKE
  ELTLVNNVLKLATKLLKELDSPFRLYGLTMNPLLYNITQVVILSAVSGVISDLLGFNLKL
  WKIKS

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein PHTF2 (PHTF2).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein PHTF2 (PHTF2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein PHTF2 (PHTF2).	[3]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein PHTF2 (PHTF2).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Protein PHTF2 (PHTF2).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Protein PHTF2 (PHTF2).	[5]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Protein PHTF2 (PHTF2).	[6]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Protein PHTF2 (PHTF2).	[7]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Protein PHTF2 (PHTF2).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein PHTF2 (PHTF2).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Protein PHTF2 (PHTF2).	[9]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Protein PHTF2 (PHTF2).	[10]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Protein PHTF2 (PHTF2).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein PHTF2 (PHTF2).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein PHTF2 (PHTF2).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein PHTF2 (PHTF2).	[15]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Protein PHTF2 (PHTF2).	[10]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Protein PHTF2 (PHTF2).	[16]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein PHTF2 (PHTF2).	[11]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [5] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [6] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [7] Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [11] 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.
• [12] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [13] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [14] 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.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] 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.