Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3FT91Y)

• DOT Name: Mitochondrial import receptor subunit TOM40B (TOMM40L)
• Synonyms: Protein TOMM40-like
• Gene Name: TOMM40L
• UniProt ID: TM40L_HUMAN
• Pfam ID: PF01459
• Sequence:
  MGNTLGLAPMGTLPRRSPRREEPLPNPGSFDELHRLCKDVFPAQMEGVKLVVNKVLSSHF
  QVAHTIHMSALGLPGYHLHAAYAGDWQLSPTEVFPTVVGDMDSSGSLNAQVLLLLAERLR
  AKAVFQTQQAKFLTWQFDGEYRGDDYTATLTLGNPDLIGESVIMVAHFLQSLTHRLVLGG
  ELVYHRRPGEEGAILTLAGKYSAVHWVATLNVGSGGAHASYYHRANEQVQVGVEFEANTR
  LQDTTFSFGYHLTLPQANMVFRGLVDSNWCVGAVLEKKMPPLPVTLALGAFLNHWRNRFH
  CGFSITVG
• Function: Potential channel-forming protein implicated in import of protein precursors into mitochondria.
• KEGG Pathway:
  Mitophagy - animal (hsa04137)
  Amyotrophic lateral sclerosis (hsa05014)
  Pathways of neurodegeneration - multiple diseases (hsa05022)

Molecular Interaction Atlas (MIA) of This DOT

10 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 Mitochondrial import receptor subunit TOM40B (TOMM40L).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Mitochondrial import receptor subunit TOM40B (TOMM40L).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Mitochondrial import receptor subunit TOM40B (TOMM40L).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mitochondrial import receptor subunit TOM40B (TOMM40L).	[4]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Mitochondrial import receptor subunit TOM40B (TOMM40L).	[5]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Mitochondrial import receptor subunit TOM40B (TOMM40L).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Mitochondrial import receptor subunit TOM40B (TOMM40L).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Mitochondrial import receptor subunit TOM40B (TOMM40L).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Mitochondrial import receptor subunit TOM40B (TOMM40L).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Mitochondrial import receptor subunit TOM40B (TOMM40L).	[11]

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 affects the methylation of Mitochondrial import receptor subunit TOM40B (TOMM40L).	[8]

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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [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] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [10] 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.
• [11] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.