Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVR7MLK)

• DOT Name: Acyl-CoA-binding domain-containing protein 4 (ACBD4)
• Gene Name: ACBD4
• UniProt ID: ACBD4_HUMAN
• PDB ID: 2WH5
• Pfam ID: PF00887
• Sequence:
  MGTEKESPEPDCQKQFQAAVSVIQNLPKNGSYRPSYEEMLRFYSYYKQATMGPCLVPRPG
  FWDPIGRYKWDAWNSLGKMSREEAMSAYITEMKLVAQKVIDTVPLGEVAEDMFGYFEPLY
  QVIPDMPRPPETFLRRVTGWKEQVVNGDVGAVSEPPCLPKEPAPPSPESHSPRDLDSEVF
  CDSLEQLEPELSSGQHLEESVIPGTAPCPPQRKRGCGAARRGPRSWTCGCWGQFEHYRRA
  CRRCRRGCRAWRACPGPLSSLTLSVRLE
• Function: Binds medium- and long-chain acyl-CoA esters and may function as an intracellular carrier of acyl-CoA esters.
• Reactome Pathway: Peroxisomal lipid metabolism (R-HSA-390918)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Acyl-CoA-binding domain-containing protein 4 (ACBD4).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Acyl-CoA-binding domain-containing protein 4 (ACBD4).	[2]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Acyl-CoA-binding domain-containing protein 4 (ACBD4).	[3]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Acyl-CoA-binding domain-containing protein 4 (ACBD4).	[3]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Acyl-CoA-binding domain-containing protein 4 (ACBD4).	[4]
Liothyronine	DM6IR3P	Approved	Liothyronine decreases the expression of Acyl-CoA-binding domain-containing protein 4 (ACBD4).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Acyl-CoA-binding domain-containing protein 4 (ACBD4).	[6]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Acyl-CoA-binding domain-containing protein 4 (ACBD4).	[8]

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 decreases the methylation of Acyl-CoA-binding domain-containing protein 4 (ACBD4).	[7]

References

• [1] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [2] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [4] 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.
• [5] Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells. Arch Toxicol. 2013 Jun;87(6):1103-13. doi: 10.1007/s00204-013-1018-4. Epub 2013 Feb 10.
• [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] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.