Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNFB9YN)

• DOT Name: Inositol monophosphatase 2 (IMPA2)
• Synonyms: IMP 2; IMPase 2; EC 3.1.3.25; Inositol-1(or 4)-monophosphatase 2; Myo-inositol monophosphatase A2
• Gene Name: IMPA2
• UniProt ID: IMPA2_HUMAN
• PDB ID: 2CZH; 2CZI; 2CZK; 2DDK; 2FVZ
• EC Number: 3.1.3.25
• Pfam ID: PF00459
• Sequence:
  MKPSGEDQAALAAGPWEECFQAAVQLALRAGQIIRKALTEEKRVSTKTSAADLVTETDHL
  VEDLIISELRERFPSHRFIAEEAAASGAKCVLTHSPTWIIDPIDGTCNFVHRFPTVAVSI
  GFAVRQELEFGVIYHCTEERLYTGRRGRGAFCNGQRLRVSGETDLSKALVLTEIGPKRDP
  ATLKLFLSNMERLLHAKAHGVRVIGSSTLALCHLASGAADAYYQFGLHCWDLAAATVIIR
  EAGGIVIDTSGGPLDLMACRVVAASTREMAMLIAQALQTINYGRDDEK
• Function: Can use myo-inositol monophosphates, scylloinositol 1,4-diphosphate, glucose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates. Has been implicated as the pharmacological target for lithium Li(+) action in brain.
• KEGG Pathway:
  Inositol phosphate metabolism (hsa00562)
  Metabolic pathways (hsa01100)
  Phosphatidylinositol sig.ling system (hsa04070)
• Reactome Pathway: Synthesis of IP2, IP, and Ins in the cytosol (R-HSA-1855183)
• BioCyc Pathway: MetaCyc:HS06822-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitomycin	DMH0ZJE	Approved	Inositol monophosphatase 2 (IMPA2) affects the response to substance of Mitomycin.	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Inositol monophosphatase 2 (IMPA2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Inositol monophosphatase 2 (IMPA2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Inositol monophosphatase 2 (IMPA2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Inositol monophosphatase 2 (IMPA2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Inositol monophosphatase 2 (IMPA2).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Inositol monophosphatase 2 (IMPA2).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Inositol monophosphatase 2 (IMPA2).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Inositol monophosphatase 2 (IMPA2).	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Inositol monophosphatase 2 (IMPA2).	[9]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Inositol monophosphatase 2 (IMPA2).	[10]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Inositol monophosphatase 2 (IMPA2).	[11]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Inositol monophosphatase 2 (IMPA2).	[12]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Inositol monophosphatase 2 (IMPA2).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Inositol monophosphatase 2 (IMPA2).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Inositol monophosphatase 2 (IMPA2).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Inositol monophosphatase 2 (IMPA2).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Inositol monophosphatase 2 (IMPA2).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Inositol monophosphatase 2 (IMPA2).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Inositol monophosphatase 2 (IMPA2).	[18]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Inositol monophosphatase 2 (IMPA2).	[19]

References

• [1] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [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] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] 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.
• [8] A comprehensive analysis of Wnt/beta-catenin signaling pathway-related genes and crosstalk pathways in the treatment of As2O3 in renal cancer. Ren Fail. 2018 Nov;40(1):331-339.
• [9] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [10] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [11] Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [16] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [17] 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.
• [18] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [19] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [20] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.