Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBB799S)

• DOT Name: Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2)
• Synonyms: EC 6.2.1.2
• Gene Name: ACSF2
• UniProt ID: ACSF2_HUMAN
• EC Number: 6.2.1.2
• Pfam ID: PF00501 ; PF13193
• Sequence:
  MAVYVGMLRLGRLCAGSSGVLGARAALSRSWQEARLQGVRFLSSREVDRMVSTPIGGLSY
  VQGCTKKHLNSKTVGQCLETTAQRVPEREALVVLHEDVRLTFAQLKEEVDKAASGLLSIG
  LCKGDRLGMWGPNSYAWVLMQLATAQAGIILVSVNPAYQAMELEYVLKKVGCKALVFPKQ
  FKTQQYYNVLKQICPEVENAQPGALKSQRLPDLTTVISVDAPLPGTLLLDEVVAAGSTRQ
  HLDQLQYNQQFLSCHDPINIQFTSGTTGSPKGATLSHYNIVNNSNILGERLKLHEKTPEQ
  LRMILPNPLYHCLGSVAGTMMCLMYGATLILASPIFNGKKALEAISRERGTFLYGTPTMF
  VDILNQPDFSSYDISTMCGGVIAGSPAPPELIRAIINKINMKDLVVAYGTTENSPVTFAH
  FPEDTVEQKAESVGRIMPHTEARIMNMEAGTLAKLNTPGELCIRGYCVMLGYWGEPQKTE
  EAVDQDKWYWTGDVATMNEQGFCKIVGRSKDMIIRGGENIYPAELEDFFHTHPKVQEVQV
  VGVKDDRMGEEICACIRLKDGEETTVEEIKAFCKGKISHFKIPKYIVFVTNYPLTISGKI
  QKFKLREQMERHLNL
• Function: Acyl-CoA synthases catalyze the initial reaction in fatty acid metabolism, by forming a thioester with CoA. Has some preference toward medium-chain substrates. Plays a role in adipocyte differentiation.
• Reactome Pathway: Mitochondrial Fatty Acid Beta-Oxidation (R-HSA-77289)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2).	[16]

19 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 Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2).	[10]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2).	[11]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2).	[12]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2).	[14]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2).	[19]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2).	[20]

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] 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.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] 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.
• [10] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] Proteomic analysis of hepatic effects of phenobarbital in mice with humanized liver. Arch Toxicol. 2022 Oct;96(10):2739-2754. doi: 10.1007/s00204-022-03338-7. Epub 2022 Jul 26.
• [13] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [16] 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.
• [17] 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.
• [18] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [19] 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.
• [20] 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.