Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBRFQF8)

• DOT Name: Probable imidazolonepropionase (AMDHD1)
• Synonyms: EC 3.5.2.7; Amidohydrolase domain-containing protein 1
• Gene Name: AMDHD1
• Related Disease: Esophageal squamous cell carcinoma
• UniProt ID: HUTI_HUMAN
• EC Number: 3.5.2.7
• Pfam ID: PF01979
• Sequence:
  MASGHSLLLENAQQVVLVCARGERFLARDALRSLAVLEGASLVVGKDGFIKAIGPADVIQ
  RQFSGETFEEIIDCSGKCILPGLVDAHTHPVWAGERVHEFAMKLAGATYMEIHQAGGGIH
  FTVERTRQATEEELFRSLQQRLQCMMRAGTTLVECKSGYGLDLETELKMLRVIERARREL
  DIGISATYCGAHSVPKGKTATEAADDIINNHLPKLKELGRNGEIHVDNIDVFCEKGVFDL
  DSTRRILQRGKDIGLQINFHGDELHPMKAAELGAELGAQAISHLEEVSDEGIVAMATARC
  SAILLPTTAYMLRLKQPRARKMLDEGVIVALGSDFNPNAYCFSMPMVMHLACVNMRMSMP
  EALAAATINAAYALGKSHTHGSLEVGKQGDLIIINSSRWEHLIYQFGGHHELIEYVIAKG
  KLIYKT
• KEGG Pathway:
  Histidine metabolism (hsa00340)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Histidine catabolism (R-HSA-70921)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Genetic Variation	[1]

9 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 Probable imidazolonepropionase (AMDHD1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Probable imidazolonepropionase (AMDHD1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Probable imidazolonepropionase (AMDHD1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Probable imidazolonepropionase (AMDHD1).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Probable imidazolonepropionase (AMDHD1).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Probable imidazolonepropionase (AMDHD1).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Probable imidazolonepropionase (AMDHD1).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Probable imidazolonepropionase (AMDHD1).	[11]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Probable imidazolonepropionase (AMDHD1).	[6]

2 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 increases the methylation of Probable imidazolonepropionase (AMDHD1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Probable imidazolonepropionase (AMDHD1).	[9]

References

• [1] Pathway, in silico and tissue-specific expression quantitative analyses of oesophageal squamous cell carcinoma genome-wide association studies data.Int J Epidemiol. 2016 Feb;45(1):206-20. doi: 10.1093/ije/dyv294. Epub 2015 Dec 3.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] 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.
• [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.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.