Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5NWOZH)

• DOT Name: Indolethylamine N-methyltransferase (INMT)
• Synonyms: Indolamine N-methyltransferase; EC 2.1.1.49; EC 2.1.1.96; Aromatic alkylamine N-methyltransferase; Amine N-methyltransferase; Arylamine N-methyltransferase; Thioether S-methyltransferase; TEMT
• Gene Name: INMT
• Related Disease:
  Hepatocellular carcinoma
  Hirschsprung disease
• UniProt ID: INMT_HUMAN
• PDB ID: 2A14
• EC Number: 2.1.1.49; 2.1.1.96
• Pfam ID: PF01234
• Sequence:
  MKGGFTGGDEYQKHFLPRDYLATYYSFDGSPSPEAEMLKFNLECLHKTFGPGGLQGDTLI
  DIGSGPTIYQVLAACDSFQDITLSDFTDRNREELEKWLKKEPGAYDWTPAVKFACELEGN
  SGRWEEKEEKLRAAVKRVLKCDVHLGNPLAPAVLPLADCVLTLLAMECACCSLDAYRAAL
  CNLASLLKPGGHLVTTVTLRLPSYMVGKREFSCVALEKEEVEQAVLDAGFDIEQLLHSPQ
  SYSVTNAANNGVCFIVARKKPGP
• Function: Functions as a thioether S-methyltransferase and is active with a variety of thioethers and the corresponding selenium and tellurium compounds, including 3-methylthiopropionaldehyde, dimethyl selenide, dimethyl telluride, 2-methylthioethylamine, 2-methylthioethanol, methyl-n-propyl sulfide and diethyl sulfide. Plays an important role in the detoxification of selenium compounds. Catalyzes the N-methylation of tryptamine and structurally related compounds.
• Tissue Specificity: Widely expressed. The highest levels were in thyroid, adrenal gland, adult and fetal lung. Intermediate levels in heart, placenta, skeletal muscle, testis, small intestine, pancreas, stomach, spinal cord, lymph node and trachea. Very low levels in adult and fetal kidney and liver, in adult spleen, thymus, ovary, colon and bone marrow. Not expressed in peripheral blood leukocytes and brain.
• KEGG Pathway:
  Tryptophan metabolism (hsa00380)
  Selenocompound metabolism (hsa00450)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Methylation of MeSeH for excretion (R-HSA-2408552)
• BioCyc Pathway: MetaCyc:HS00305-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Hirschsprung disease	DISUUSM1	moderate	Genetic Variation	[2]

3 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 Indolethylamine N-methyltransferase (INMT).	[3]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Indolethylamine N-methyltransferase (INMT).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Indolethylamine N-methyltransferase (INMT).	[6]

1 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 Indolethylamine N-methyltransferase (INMT).	[5]

References

• [1] Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells initro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology. 2017 Jun;152(8):2022-2036.
• [2] Potential Association of INMT Nonsynonymous Variant (His46Pro) with Hirschsprung's Disease.Neonatology. 2015;108(3):164-71. doi: 10.1159/000435874. Epub 2015 Jul 15.
• [3] 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.
• [4] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [5] 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.
• [6] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.