Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9YEJXS)

• DOT Name: Inositol 1,4,5-trisphosphate receptor-interacting protein (ITPRIP)
• Synonyms: Protein DANGER
• Gene Name: ITPRIP
• Related Disease:
  Hepatitis C virus infection
  Plasma cell myeloma
  Lupus nephritis
  Advanced cancer
• UniProt ID: IPRI_HUMAN
• Pfam ID: PF20266
• Sequence:
  MAMGLFRVCLVVVTAIINHPLLFPRENATVPENEEEIIRKMQAHQEKLQLEQLRLEEEVA
  RLAAEKEALEQVAEEGRQQNETRVAWDLWSTLCMILFLMIEVWRQDHQEGPSPECLGGEE
  DELPGLGGAPLQGLTLPNKATLGHFYERCIRGATADAARTREFLEGFVDDLLEALRSLCN
  RDTDMEVEDFIGVDSMYENWQVDRPLLCHLFVPFTPPEPYRFHPELWCSGRSVPLDRQGY
  GQIKVVRADGDTLSCICGKTKLGEDMLCLLHGRNSMAPPCGDMENLLCATDSLYLDTMQV
  MKWFQTALTRAWKGIAHKYEFDLAFGQLDSPGSLKIKFRSGKFMPFNLIPVIQCDDSDLY
  FVSHLPREPSEGTPASSTDWLLSFAVYERHFLRTTLKALPEGACHLSCLQIASFLLSKQS
  RLTGPSGLSSYHLKTALLHLLLLRQAADWKAGQLDARLHELLCFLEKSLLQKKLHHFFIG
  NRKVPEAMGLPEAVLRAEPLNLFRPFVLQRSLYRKTLDSFYEMLKNAPALISEYSLHVPS
  DQPTPKS
• Function: Enhances Ca(2+)-mediated inhibition of inositol 1,4,5-triphosphate receptor (ITPR) Ca(2+) release.
• Tissue Specificity: Detected in brain where it is concentrated in cerebellar Purkinje cells (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[1]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[2]
Lupus nephritis	DISCVGPZ	moderate	Biomarker	[3]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[4]

19 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 1,4,5-trisphosphate receptor-interacting protein (ITPRIP).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein (ITPRIP).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein (ITPRIP).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein (ITPRIP).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein (ITPRIP).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein (ITPRIP).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein (ITPRIP).	[11]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein (ITPRIP).	[12]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein (ITPRIP).	[13]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein (ITPRIP).	[14]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein (ITPRIP).	[15]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein (ITPRIP).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein (ITPRIP).	[17]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein (ITPRIP).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein (ITPRIP).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein (ITPRIP).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein (ITPRIP).	[21]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein (ITPRIP).	[22]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein (ITPRIP).	[23]

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 Inositol 1,4,5-trisphosphate receptor-interacting protein (ITPRIP).	[16]

References

• [1] Long Noncoding RNA ITPRIP-1 Positively Regulates the Innate Immune Response through Promotion of Oligomerization and Activation of MDA5.J Virol. 2018 Aug 16;92(17):e00507-18. doi: 10.1128/JVI.00507-18. Print 2018 Sep 1.
• [2] Early tumor-cell gene expression changes may predict the response to first-line bortezomib-based therapy in patients with newly diagnosed multiple myeloma.J BUON. 2015 Sep-Oct;20(5):1314-21.
• [3] Elevated expressions of myeloid-related proteins-8 and -14 are danger biomarkers for lupus nephritis.Lupus. 2016 Jan;25(1):38-45. doi: 10.1177/0961203315598015. Epub 2015 Jul 29.
• [4] Exploiting scavenger receptors in cancer immunotherapy: Lessons from CD5 and SR-B1.Eur J Immunol. 2017 Jul;47(7):1108-1118. doi: 10.1002/eji.201646903. Epub 2017 Jun 12.
• [5] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [6] 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.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [12] Estrogenic GPR30 signalling induces proliferation and migration of breast cancer cells through CTGF. EMBO J. 2009 Mar 4;28(5):523-32.
• [13] 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.
• [14] 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.
• [15] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [16] 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.
• [17] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [18] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [23] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.