Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3T9HAX)

• DOT Name: Acyl-CoA dehydrogenase family member 11 (ACAD11)
• Synonyms: ACAD-11; EC 1.3.8.-
• Gene Name: ACAD11
• UniProt ID: ACD11_HUMAN
• PDB ID: 2WBI
• EC Number: 1.3.8.-
• Pfam ID: PF00441 ; PF02770 ; PF02771 ; PF01636
• Sequence:
  MKPGATGESDLAEVLPQHKFDSKSLEAYLNQHLSGFGAEREATLTIAQYRAGKSNPTFYL
  QKGFQTYVLRKKPPGSLLPKAHQIDREFKVQKALFSIGFPVPKPILYCSDTSVIGTEFYV
  MEHVQGRIFRDLTIPGLSPAERSAIYVATVETLAQLHSLNIQSLQLEGYGIGAGYCKRQV
  STWTKQYQAAAHQDIPAMQQLSEWLMKNLPDNDNEENLIHGDFRLDNIVFHPKECRVIAV
  LDWELSTIGHPLSDLAHFSLFYFWPRTVPMINQGSYSENSGIPSMEELISIYCRCRGINS
  ILPNWNFFLALSYFKMAGIAQGVYSRYLLGNNSSEDSFLFANIVQPLAETGLQLSKRTFS
  TVLPQIDTTGQLFVQTRKGQEVLIKVKHFMKQHILPAEKEVTEFYVQNENSVDKWGKPLV
  IDKLKEMAKVEGLWNLFLPAVSGLSHVDYALIAEETGKCFFAPDVFNCQAPDTGNMEVLH
  LYGSEEQKKQWLEPLLQGNITSCFCMTEPDVASSDATNIECSIQRDEDSYVINGKKWWSS
  GAGNPKCKIAIVLGRTQNTSLSRHKQHSMILVPMNTPGVKIIRPLSVFGYTDNFHGGHFE
  IHFNQVRVPATNLILGEGRGFEISQGRLGPGRIHHCMRTVGLAERALQIMCERATQRIAF
  KKKLYAHEVVAHWIAESRIAIEKIRLLTLKAAHSMDTLGSAGAKKEIAMIKVAAPRAVSK
  IVDWAIQVCGGAGVSQDYPLANMYAITRVLRLADGPDEVHLSAIATMELRDQAKRLTAKI
• Function: Acyl-CoA dehydrogenase, that exhibits maximal activity towards saturated C22-CoA. Probably participates in beta-oxydation and energy production but could also play a role in the metabolism of specific fatty acids to control fatty acids composition of cellular lipids in brain (Probable).
• Tissue Specificity: Widely expressed with highest levels in brain followed by liver, heart and kidney.
• 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 Acyl-CoA dehydrogenase family member 11 (ACAD11).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Acyl-CoA dehydrogenase family member 11 (ACAD11).	[12]

15 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 dehydrogenase family member 11 (ACAD11).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Acyl-CoA dehydrogenase family member 11 (ACAD11).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Acyl-CoA dehydrogenase family member 11 (ACAD11).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Acyl-CoA dehydrogenase family member 11 (ACAD11).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Acyl-CoA dehydrogenase family member 11 (ACAD11).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Acyl-CoA dehydrogenase family member 11 (ACAD11).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Acyl-CoA dehydrogenase family member 11 (ACAD11).	[4]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Acyl-CoA dehydrogenase family member 11 (ACAD11).	[8]
Chenodiol	DMQ8JIK	Approved	Chenodiol decreases the expression of Acyl-CoA dehydrogenase family member 11 (ACAD11).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Acyl-CoA dehydrogenase family member 11 (ACAD11).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Acyl-CoA dehydrogenase family member 11 (ACAD11).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Acyl-CoA dehydrogenase family member 11 (ACAD11).	[2]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Acyl-CoA dehydrogenase family member 11 (ACAD11).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Acyl-CoA dehydrogenase family member 11 (ACAD11).	[13]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Acyl-CoA dehydrogenase family member 11 (ACAD11).	[7]

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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [9] Chenodeoxycholic acid significantly impacts the expression of miRNAs and genes involved in lipid, bile acid and drug metabolism in human hepatocytes. Life Sci. 2016 Jul 1;156:47-56.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [12] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [13] 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.