Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBUVW1Z)

DOT Name	Inositol monophosphatase 1 (IMPA1)
Synonyms	IMP 1; IMPase 1; EC 3.1.3.25; D-galactose 1-phosphate phosphatase; EC 3.1.3.94; Inositol-1(or 4)-monophosphatase 1; Lithium-sensitive myo-inositol monophosphatase A1
Gene Name	IMPA1
Related Disease	Bacteremia ( ) Cryptosporidium infection ( ) Lewy body dementia ( ) Mycoses ( ) Bipolar disorder ( ) Breast neoplasm ( ) Cardiac disease ( ) Cerebral infarction ( ) Chromosomal disorder ( ) Colon cancer ( ) Colon carcinoma ( ) Glioma ( ) Glycogen storage disease VII ( ) Lung cancer ( ) Lung carcinoma ( ) Muscular dystrophy ( ) Neoplasm ( ) Neuralgia ( ) Ovarian cancer ( ) Pseudomonas infection ( ) Retinitis pigmentosa ( ) Advanced cancer ( ) Alcohol dependence ( ) Alzheimer disease ( ) Blast phase chronic myelogenous leukemia, BCR-ABL1 positive ( ) Conjunctivitis ( ) Cystitis ( ) Epithelial ovarian cancer ( ) High blood pressure ( ) Intellectual disability, autosomal recessive 59 ( ) Non-insulin dependent diabetes ( ) Ovarian neoplasm ( ) Sickle-cell anaemia ( ) Systemic primary carnitine deficiency disease ( )
UniProt ID	IMPA1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1AWB; 1IMA; 1IMB; 1IMC; 1IMD; 1IME; 1IMF; 2HHM; 4AS4; 6GIU; 6GJ0; 6ZK0; 7VCE
EC Number	3.1.3.25; 3.1.3.94
Pfam ID	PF00459
Sequence	MADPWQECMDYAVTLARQAGEVVCEAIKNEMNVMLKSSPVDLVTATDQKVEKMLISSIKE KYPSHSFIGEESVAAGEKSILTDNPTWIIDPIDGTTNFVHRFPFVAVSIGFAVNKKIEFG VVYSCVEGKMYTARKGKGAFCNGQKLQVSQQEDITKSLLVTELGSSRTPETVRMVLSNME KLFCIPVHGIRSVGTAAVNMCLVATGGADAYYEMGIHCWDVAGAGIIVTEAGGVLMDVTG GPFDLMSRRVIAANNRILAERIAKEIQVIPLQRDDED
Function	Responsible for the provision of inositol required for synthesis of phosphatidylinositol and polyphosphoinositides and has been implicated as the pharmacological target for lithium action in brain. Has broad substrate specificity and can use myo-inositol monophosphates, myo-inositol 1,3-diphosphate, myo-inositol 1,4-diphosphate, scyllo-inositol-phosphate, D-galactose 1-phosphate, glucose-1-phosphate, glucose-6-phosphate, fructose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates.
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:HS05783-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Bacteremia	DIS6N9RZ	Definitive	Biomarker	[1]
Cryptosporidium infection	DISLBTU2	Definitive	Biomarker	[2]
Lewy body dementia	DISAE66J	Definitive	Biomarker	[3]
Mycoses	DIS9K7PB	Definitive	Biomarker	[4]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[6]
Cardiac disease	DISVO1I5	Strong	Biomarker	[7]
Cerebral infarction	DISR1WNP	Strong	Biomarker	[8]
Chromosomal disorder	DISM5BB5	Strong	Biomarker	[9]
Colon cancer	DISVC52G	Strong	Biomarker	[10]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[11]
Glioma	DIS5RPEH	Strong	Biomarker	[12]
Glycogen storage disease VII	DISWZUF2	Strong	Altered Expression	[13]
Lung cancer	DISCM4YA	Strong	Altered Expression	[14]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[14]
Muscular dystrophy	DISJD6P7	Strong	Biomarker	[15]
Neoplasm	DISZKGEW	Strong	Biomarker	[16]
Neuralgia	DISWO58J	Strong	Biomarker	[17]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[18]
Pseudomonas infection	DIS9WYLA	Strong	Biomarker	[19]
Retinitis pigmentosa	DISCGPY8	Strong	Biomarker	[20]
Advanced cancer	DISAT1Z9	moderate	Genetic Variation	[21]
Alcohol dependence	DIS4ZSCO	moderate	Biomarker	[22]
Alzheimer disease	DISF8S70	Limited	Biomarker	[3]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	Limited	Altered Expression	[23]
Conjunctivitis	DISGOZ4P	Limited	Biomarker	[24]
Cystitis	DIS2D4B9	Limited	Biomarker	[24]
Epithelial ovarian cancer	DIS56MH2	Limited	Biomarker	[18]
High blood pressure	DISY2OHH	Limited	Biomarker	[25]
Intellectual disability, autosomal recessive 59	DIS1HFXK	Limited	Autosomal recessive	[26]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[27]
Ovarian neoplasm	DISEAFTY	Limited	Biomarker	[18]
Sickle-cell anaemia	DIS5YNZB	Limited	Biomarker	[28]
Systemic primary carnitine deficiency disease	DIS9OPZ4	Limited	Biomarker	[28]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas 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 Inositol monophosphatase 1 (IMPA1).	[29]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Inositol monophosphatase 1 (IMPA1).	[30]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Inositol monophosphatase 1 (IMPA1).	[31]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Inositol monophosphatase 1 (IMPA1).	[32]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Inositol monophosphatase 1 (IMPA1).	[33]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Inositol monophosphatase 1 (IMPA1).	[34]
Marinol	DM70IK5	Approved	Marinol affects the expression of Inositol monophosphatase 1 (IMPA1).	[35]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Inositol monophosphatase 1 (IMPA1).	[36]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Inositol monophosphatase 1 (IMPA1).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Inositol monophosphatase 1 (IMPA1).	[38]
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⏷ Show the Full List of 10 Drug(s)

References

1	Molecular and epidemiological characterization of IMP-type metallo--lactamase-producing Enterobacter cloacae in a Large tertiary care hospital in Japan.Antimicrob Agents Chemother. 2014 Jun;58(6):3441-50. doi: 10.1128/AAC.02652-13. Epub 2014 Apr 7.
2	Validation of IMP dehydrogenase inhibitors in a mouse model of cryptosporidiosis.Antimicrob Agents Chemother. 2014;58(3):1603-14. doi: 10.1128/AAC.02075-13. Epub 2013 Dec 23.
3	The Cingulate Island Sign on FDG-PET vs. IMP-SPECT to Assess Mild Cognitive Impairment in Alzheimer's Disease vs. Dementia with Lewy Bodies.J Neuroimaging. 2019 Nov;29(6):712-720. doi: 10.1111/jon.12643. Epub 2019 Jun 14.
4	Molecular and epidemiological analysis of IMP-1 metallo--lactamase-producing Klebsiella pneumoniae in a tertiary care hospital in Japan.J Infect Chemother. 2019 Apr;25(4):240-246. doi: 10.1016/j.jiac.2018.11.012. Epub 2019 Jan 2.
5	A homozygous loss-of-function mutation in inositol monophosphatase 1 (IMPA1) causes severe intellectual disability. Mol Psychiatry. 2016 Aug;21(8):1125-9. doi: 10.1038/mp.2015.150. Epub 2015 Sep 29.
6	IMP3 promotes TNBC stem cell property through miRNA-34a regulation.Eur Rev Med Pharmacol Sci. 2018 May;22(9):2688-2696. doi: 10.26355/eurrev_201805_14965.
7	Patterns of Multimorbidity in a Population-Based Cohort of Older People: Sociodemographic, Lifestyle, Clinical, and Functional Differences.J Gerontol A Biol Sci Med Sci. 2020 Mar 9;75(4):798-805. doi: 10.1093/gerona/glz137.
8	pSY153-MDR, a p12969-DIM-related mega plasmid carrying bla(IMP-45) and armA, from clinical Pseudomonas putida.Oncotarget. 2017 Jul 22;8(40):68439-68447. doi: 10.18632/oncotarget.19496. eCollection 2017 Sep 15.
9	ITPA protein, an enzyme that eliminates deaminated purine nucleoside triphosphates in cells.Mutat Res. 2010 Nov 28;703(1):43-50. doi: 10.1016/j.mrgentox.2010.06.009. Epub 2010 Jun 22.
10	Antimicrobial susceptibilities of specific syndromes created with organ-specific weighted incidence antibiograms (OSWIA) in patients with intra-abdominal infections.BMC Infect Dis. 2018 Nov 19;18(1):584. doi: 10.1186/s12879-018-3494-x.
11	IMP-1 displays cross-talk with K-Ras and modulates colon cancer cell survival through the novel proapoptotic protein CYFIP2.Cancer Res. 2011 Mar 15;71(6):2172-82. doi: 10.1158/0008-5472.CAN-10-3295. Epub 2011 Jan 20.
12	Autophagy suppression sensitizes glioma cells to IMP dehydrogenase inhibition-induced apoptotic death.Exp Cell Res. 2017 Jan 1;350(1):32-40. doi: 10.1016/j.yexcr.2016.11.001. Epub 2016 Nov 4.
13	The contribution of Ca+ calmodulin activation of human erythrocyte AMP deaminase (isoform E) to the erythrocyte metabolic dysregulation of familial phosphofructokinase deficiency.Haematologica. 2006 May;91(5):652-5.
14	Increased expression of insulin-like growth factor-II messenger RNA-binding protein 1 is associated with tumor progression in patients with lung cancer.Clin Cancer Res. 2007 Jan 15;13(2 Pt 1):434-42. doi: 10.1158/1078-0432.CCR-06-1297.
15	Fine mapping of the muscular dystrophy (AM) gene on chicken chromosome 2q.Anim Genet. 2004 Oct;35(5):397-400. doi: 10.1111/j.1365-2052.2004.01171.x.
16	Immuno-PET quantitation of de2-7 epidermal growth factor receptor expression in glioma using 124I-IMP-R4-labeled antibody ch806.J Nucl Med. 2010 Jun;51(6):967-72. doi: 10.2967/jnumed.109.068395. Epub 2010 May 19.
17	Altered cerebral blood flow in the anterior cingulate cortex is associated with neuropathic pain.J Neurol Neurosurg Psychiatry. 2018 Oct;89(10):1082-1087. doi: 10.1136/jnnp-2017-316601. Epub 2018 Apr 7.
18	Let-7 modulates acquired resistance of ovarian cancer to Taxanes via IMP-1-mediated stabilization of multidrug resistance 1.Int J Cancer. 2012 Apr 15;130(8):1787-97. doi: 10.1002/ijc.26190. Epub 2011 Aug 16.
19	Nosocomial infections caused by multidrug-resistant isolates of pseudomonas putida producing VIM-1 metallo-beta-lactamase.J Clin Microbiol. 2002 Nov;40(11):4051-5. doi: 10.1128/JCM.40.11.4051-4055.2002.
20	IMP dehydrogenase-linked retinitis pigmentosa.Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):839-49. doi: 10.1080/15257770802146486.
21	IMP-6 Carbapenemase-Producing Enterobacteriaceae Bacteremia Successfully Treated with Amikacin-Meropenem in Two Patients.Pharmacotherapy. 2017 Oct;37(10):e96-e102. doi: 10.1002/phar.1984. Epub 2017 Aug 23.
22	Genetic and environmental influences on externalizing behavior and alcohol problems in adolescence: a female twin study.Pharmacol Biochem Behav. 2009 Sep;93(3):313-21. doi: 10.1016/j.pbb.2009.03.011. Epub 2009 Mar 31.
23	Tiazofurin effects on IMP-dehydrogenase activity and expression in the leukemia cells of patients with CML blast crisis.Anticancer Res. 1996 Nov-Dec;16(6A):3349-51.
24	Analysis of IMP-1 type metallo--lactamase-producing Acinetobacter radioresistens isolated from companion animals.J Infect Chemother. 2017 Sep;23(9):655-657. doi: 10.1016/j.jiac.2017.03.011. Epub 2017 Apr 10.
25	Inositol monophosphatase 1 as a novel interacting partner of RAGE in pulmonary hypertension.Am J Physiol Lung Cell Mol Physiol. 2019 Mar 1;316(3):L428-L444. doi: 10.1152/ajplung.00393.2018. Epub 2019 Jan 3.
26	Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
27	IGF2 mRNA-binding protein 2: biological function and putative role in type 2 diabetes.J Mol Endocrinol. 2009 Nov;43(5):187-95. doi: 10.1677/JME-09-0016. Epub 2009 May 8.
28	Arterial spin labeling MR imaging for the clinical detection of cerebellar hypoperfusion in patients with spinocerebellar degeneration.J Neurol Sci. 2018 Nov 15;394:58-62. doi: 10.1016/j.jns.2018.09.007. Epub 2018 Sep 6.
29	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
30	Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
31	Expression Profiling of Human Pluripotent Stem Cell-Derived Cardiomyocytes Exposed to Doxorubicin-Integration and Visualization of Multi-Omics Data. Toxicol Sci. 2018 May 1;163(1):182-195. doi: 10.1093/toxsci/kfy012.
32	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
33	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.
34	The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
35	JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
36	Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
37	New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
38	Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.