Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9EIUGH)

• DOT Name: Phytanoyl-CoA hydroxylase-interacting protein-like (PHYHIPL)
• Gene Name: PHYHIPL
• Related Disease:
  Glioblastoma multiforme
  Glioma
• UniProt ID: PHIPL_HUMAN
• Pfam ID: PF00041 ; PF19281
• Sequence:
  MEVPRLDHALNSPTSPCEEVIKNLSLEAIQLCDRDGNKSQDSGIAEMEELPVPHNIKISN
  ITCDSFKISWEMDSKSKDRITHYFIDLNKKENKNSNKFKHKDVPTKLVAKAVPLPMTVRG
  HWFLSPRTEYTVAVQTASKQVDGDYVVSEWSEIIEFCTADYSKVHLTQLLEKAEVIAGRM
  LKFSVFYRNQHKEYFDYVREHHGNAMQPSVKDNSGSHGSPISGKLEGIFFSCSTEFNTGK
  PPQDSPYGRYRFEIAAEKLFNPNTNLYFGDFYCMYTAYHYVILVIAPVGSPGDEFCKQRL
  PQLNSKDNKFLTCTEEDGVLVYHHAQDVILEVIYTDPVDLSVGTVAEITGHQLMSLSTAN
  AKKDPSCKTCNISVGR
• Function: May play a role in the development of the central system.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[1]
Glioma	DIS5RPEH	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Phytanoyl-CoA hydroxylase-interacting protein-like (PHYHIPL).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Phytanoyl-CoA hydroxylase-interacting protein-like (PHYHIPL).	[3]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Phytanoyl-CoA hydroxylase-interacting protein-like (PHYHIPL).	[4]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Phytanoyl-CoA hydroxylase-interacting protein-like (PHYHIPL).	[5]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Phytanoyl-CoA hydroxylase-interacting protein-like (PHYHIPL).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Phytanoyl-CoA hydroxylase-interacting protein-like (PHYHIPL).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Phytanoyl-CoA hydroxylase-interacting protein-like (PHYHIPL).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Phytanoyl-CoA hydroxylase-interacting protein-like (PHYHIPL).	[10]

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 Phytanoyl-CoA hydroxylase-interacting protein-like (PHYHIPL).	[8]

References

• [1] Phytanoyl-CoA 2-Hydroxylase-Interacting Protein-Like Gene Is a Therapeutic Target Gene for Glioblastoma Multiforme.Med Sci Monit. 2019 Apr 9;25:2583-2590. doi: 10.12659/MSM.913895.
• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [10] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.