Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXE3X5J)

• DOT Name: Manganese-dependent ADP-ribose/CDP-alcohol diphosphatase (ADPRM)
• Synonyms: EC 3.6.1.13; EC 3.6.1.16; EC 3.6.1.53; ADPRibase-Mn; CDP-choline phosphohydrolase
• Gene Name: ADPRM
• UniProt ID: ADPRM_HUMAN
• EC Number: 3.6.1.13; 3.6.1.16; 3.6.1.53
• Pfam ID: PF00149
• Sequence:
  MDDKPNPEALSDSSERLFSFGVIADVQFADLEDGFNFQGTRRRYYRHSLLHLQGAIEDWN
  NESSMPCCVLQLGDIIDGYNAQYNASKKSLELVMDMFKRLKVPVHHTWGNHEFYNFSREY
  LTHSKLNTKFLEDQIVHHPETMPSEDYYAYHFVPFPKFRFILLDAYDLSVLGVDQSSPKY
  EQCMKILREHNPNTELNSPQGLSEPQFVQFNGGFSQEQLNWLNEVLTFSDTNQEKVVIVS
  HLPIYPDASDNVCLAWNYRDALAVIWSHECVVCFFAGHTHDGGYSEDPFGVYHVNLEGVI
  ETAPDSQAFGTVHVYPDKMMLKGRGRVPDRIMNYKKERAFHC
• Function: Hydrolyzes ADP-ribose, IDP-ribose, CDP-glycerol, CDP-choline and CDP-ethanolamine, but not other non-reducing ADP-sugars or CDP-glucose. May be involved in immune cell signaling as suggested by the second-messenger role of ADP-ribose, which activates TRPM2 as a mediator of oxidative/nitrosative stress.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Glycerophospholipid metabolism (hsa00564)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Phosphate bond hydrolysis by NUDT proteins (R-HSA-2393930)

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 Manganese-dependent ADP-ribose/CDP-alcohol diphosphatase (ADPRM).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Manganese-dependent ADP-ribose/CDP-alcohol diphosphatase (ADPRM).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Manganese-dependent ADP-ribose/CDP-alcohol diphosphatase (ADPRM).	[3]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Manganese-dependent ADP-ribose/CDP-alcohol diphosphatase (ADPRM).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Manganese-dependent ADP-ribose/CDP-alcohol diphosphatase (ADPRM).	[6]
Enzalutamide	DMGL19D	Approved	Enzalutamide decreases the expression of Manganese-dependent ADP-ribose/CDP-alcohol diphosphatase (ADPRM).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Manganese-dependent ADP-ribose/CDP-alcohol diphosphatase (ADPRM).	[8]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Manganese-dependent ADP-ribose/CDP-alcohol diphosphatase (ADPRM).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Manganese-dependent ADP-ribose/CDP-alcohol diphosphatase (ADPRM).	[9]
CH-223191	DMMJZYC	Investigative	CH-223191 increases the expression of Manganese-dependent ADP-ribose/CDP-alcohol diphosphatase (ADPRM).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Manganese-dependent ADP-ribose/CDP-alcohol diphosphatase (ADPRM).	[4]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] 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] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] 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.
• [6] 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.
• [7] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.