Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTODDR21)

• DOT Name: Alpha-tocopherol transfer protein-like
• Gene Name: TTPAL
• UniProt ID: TTPAL_HUMAN
• Pfam ID: PF00650 ; PF03765
• Sequence:
  MSEESDSLRTSPSVASLSENELPPPPEPPGYVCSLTEDLVTKAREELQEKPEWRLRDVQA
  LRDMVRKEYPNLSTSLDDAFLLRFLRARKFDYDRALQLLVNYHSCRRSWPEVFNNLKPSA
  LKDVLASGFLTVLPHTDPRGCHVVCIRPDRWIPSNYPITENIRAIYLTLEKLIQSEETQV
  NGIVILADYKGVSLSKASHFGPFIAKKVIGILQDGFPIRIKAVHVVNEPRIFKGIFAIIK
  PFLKEKIANRFFLHGSDLNSLHTNLPRSILPKEYGGTAGELDTATWNAVLLASEDDFVKE
  FCQPVPACDSILGQTLLPEGLTSDAQCDDSLRAVKSQLYSCY
• Function: May act as a protein that binds a hydrophobic ligand.

Molecular Interaction Atlas (MIA) of This DOT

9 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 Alpha-tocopherol transfer protein-like.	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Alpha-tocopherol transfer protein-like.	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Alpha-tocopherol transfer protein-like.	[3]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Alpha-tocopherol transfer protein-like.	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Alpha-tocopherol transfer protein-like.	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Alpha-tocopherol transfer protein-like.	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Alpha-tocopherol transfer protein-like.	[9]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Alpha-tocopherol transfer protein-like.	[10]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Alpha-tocopherol transfer protein-like.	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Alpha-tocopherol transfer protein-like.	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Alpha-tocopherol transfer protein-like.	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [10] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
• [11] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.