Details of Drug Off-Target (DOT)

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

• DOT Name: Catechol O-methyltransferase domain-containing protein 1 (COMTD1)
• Synonyms: EC 2.1.1.-
• Gene Name: COMTD1
• Related Disease: Schizophrenia
• UniProt ID: CMTD1_HUMAN
• PDB ID: 2AVD
• EC Number: 2.1.1.-
• Pfam ID: PF01596
• Sequence:
  MTQPVPRLSVPAALALGSAALGAAFATGLFLGRRCPPWRGRREQCLLPPEDSRLWQYLLS
  RSMREHPALRSLRLLTLEQPQGDSMMTCEQAQLLANLARLIQAKKALDLGTFTGYSALAL
  ALALPADGRVVTCEVDAQPPELGRPLWRQAEAEHKIDLRLKPALETLDELLAAGEAGTFD
  VAVVDADKENCSAYYERCLQLLRPGGILAVLRVLWRGKVLQPPKGDVAAECVRNLNERIR
  RDVRVYISLLPLGDGLTLAFKI
• Function: Putative O-methyltransferase.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Catechol O-methyltransferase domain-containing protein 1 (COMTD1).	[2]

12 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Catechol O-methyltransferase domain-containing protein 1 (COMTD1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Catechol O-methyltransferase domain-containing protein 1 (COMTD1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Catechol O-methyltransferase domain-containing protein 1 (COMTD1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Catechol O-methyltransferase domain-containing protein 1 (COMTD1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Catechol O-methyltransferase domain-containing protein 1 (COMTD1).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Catechol O-methyltransferase domain-containing protein 1 (COMTD1).	[8]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Catechol O-methyltransferase domain-containing protein 1 (COMTD1).	[9]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Catechol O-methyltransferase domain-containing protein 1 (COMTD1).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Catechol O-methyltransferase domain-containing protein 1 (COMTD1).	[9]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Catechol O-methyltransferase domain-containing protein 1 (COMTD1).	[11]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Catechol O-methyltransferase domain-containing protein 1 (COMTD1).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Catechol O-methyltransferase domain-containing protein 1 (COMTD1).	[12]

References

• [1] Comprehensive DNA methylation analysis of peripheral blood cells derived from patients with first-episode schizophrenia.J Hum Genet. 2013 Feb;58(2):91-7. doi: 10.1038/jhg.2012.140. Epub 2012 Dec 13.
• [2] 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.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] 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.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [12] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.