Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS64ZTB)

• DOT Name: Adenosine deaminase-like protein (ADAL)
• Synonyms: EC 3.5.4.-; Adenosine deaminase-like protein isoform 1; N6-mAMP deaminase; HsMAPDA; N6-methyl-AMP aminohydrolase
• Gene Name: ADAL
• UniProt ID: ADAL_HUMAN
• EC Number: 3.5.4.-
• Pfam ID: PF00962
• Sequence:
  MIEAEEQQPCKTDFYSELPKVELHAHLNGSISSHTMKKLIAQKPDLKIHDQMTVIDKGKK
  RTLEECFQMFQTIHQLTSSPEDILMVTKDVIKEFADDGVKYLELRSTPRRENATGMTKKT
  YVESILEGIKQSKQENLDIDVRYLIAVDRRGGPLVAKETVKLAEEFFLSTEGTVLGLDLS
  GDPTVGQAKDFLEPLLEAKKAGLKLALHLSEIPNQKKETQILLDLLPDRIGHGTFLNSGE
  GGSLDLVDFVRQHRIPLELCLTSNVKSQTVPSYDQHHFGFWYSIAHPSVICTDDKGVFAT
  HLSQEYQLAAETFNLTQSQVWDLSYESINYIFASDSTRSELRKKWNHLKPRVLHI
• Function: Catalyzes the hydrolysis of the free cytosolic methylated adenosine nucleotide N(6)-methyl-AMP (N6-mAMP) to produce inositol monophosphate (IMP) and methylamine. Is required for the catabolism of cytosolic N6-mAMP, which is derived from the degradation of mRNA containing N6-methylated adenine (m6A). Catalyzes the removal of different alkyl groups not only from N6-substituted purine or 2-aminopurine nucleoside monophosphates but also from O6-substituted compounds in vitro.
• Reactome Pathway:
  Purine salvage (R-HSA-74217)
  Abacavir metabolism (R-HSA-2161541)
• BioCyc Pathway: MetaCyc:ENSG00000168803-MONOMER

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 Adenosine deaminase-like protein (ADAL).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Adenosine deaminase-like protein (ADAL).	[8]

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 Adenosine deaminase-like protein (ADAL).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Adenosine deaminase-like protein (ADAL).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Adenosine deaminase-like protein (ADAL).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Adenosine deaminase-like protein (ADAL).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Adenosine deaminase-like protein (ADAL).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Adenosine deaminase-like protein (ADAL).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Adenosine deaminase-like protein (ADAL).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Adenosine deaminase-like protein (ADAL).	[10]

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] 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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] 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.
• [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] 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.
• [10] 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.