Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKS4P2T)

• DOT Name: Inositol hexakisphosphate kinase 1 (IP6K1)
• Synonyms: InsP6 kinase 1; EC 2.7.4.21; Inositol hexaphosphate kinase 1
• Gene Name: IP6K1
• Related Disease:
  Anal intraepithelial neoplasia
  Bacterial pneumonia
  Fatty liver disease
  Type-1/2 diabetes
  Non-insulin dependent diabetes
  Obesity
• UniProt ID: IP6K1_HUMAN
• EC Number: 2.7.4.21
• Pfam ID: PF03770
• Sequence:
  MCVCQTMEVGQYGKNASRAGDRGVLLEPFIHQVGGHSSMMRYDDHTVCKPLISREQRFYE
  SLPPEMKEFTPEYKGVVSVCFEGDSDGYINLVAYPYVESETVEQDDTTEREQPRRKHSRR
  SLHRSGSGSDHKEEKASLSLETSESSQEAKSPKVELHSHSEVPFQMLDGNSGLSSEKISH
  NPWSLRCHKQQLSRMRSESKDRKLYKFLLLENVVHHFKYPCVLDLKMGTRQHGDDASAEK
  AARQMRKCEQSTSATLGVRVCGMQVYQLDTGHYLCRNKYYGRGLSIEGFRNALYQYLHNG
  LDLRRDLFEPILSKLRGLKAVLERQASYRFYSSSLLVIYDGKECRAESCLDRRSEMRLKH
  LDMVLPEVASSCGPSTSPSNTSPEAGPSSQPKVDVRMIDFAHSTFKGFRDDPTVHDGPDR
  GYVFGLENLISIMEQMRDENQ
• Function: Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5). Converts 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4.
• KEGG Pathway: Phosphatidylinositol sig.ling system (hsa04070)
• Reactome Pathway:
  Synthesis of IPs in the nucleus (R-HSA-1855191)
  Synthesis of pyrophosphates in the cytosol (R-HSA-1855167)
• BioCyc Pathway: MetaCyc:HS10997-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anal intraepithelial neoplasia	DISJ0JW3	Strong	Biomarker	[1]
Bacterial pneumonia	DISPW7PH	Strong	Biomarker	[2]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[3]
Type-1/2 diabetes	DISIUHAP	Disputed	Biomarker	[4]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[5]
Obesity	DIS47Y1K	Limited	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Inositol hexakisphosphate kinase 1 (IP6K1).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Inositol hexakisphosphate kinase 1 (IP6K1).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Inositol hexakisphosphate kinase 1 (IP6K1).	[9]
LY294002	DMY1AFS	Phase 1	LY294002 decreases the activity of Inositol hexakisphosphate kinase 1 (IP6K1).	[10]

References

• [1] Deletion of inositol hexakisphosphate kinase 1 (IP6K1) reduces cell migration and invasion, conferring protection from aerodigestive tract carcinoma in mice.Cell Signal. 2016 Aug;28(8):1124-36. doi: 10.1016/j.cellsig.2016.04.011. Epub 2016 Apr 30.
• [2] Inhibition of IP6K1 suppresses neutrophil-mediated pulmonary damage in bacterial pneumonia.Sci Transl Med. 2018 Apr 4;10(435):eaal4045. doi: 10.1126/scitranslmed.aal4045.
• [3] Global IP6K1 deletion enhances temperature modulated energy expenditure which reduces carbohydrate and fat induced weight gain.Mol Metab. 2016 Nov 28;6(1):73-85. doi: 10.1016/j.molmet.2016.11.010. eCollection 2017 Jan.
• [4] Inositol hexakisphosphate kinase 1 is a metabolic sensor in pancreatic -cells.Cell Signal. 2018 Jun;46:120-128. doi: 10.1016/j.cellsig.2018.03.001. Epub 2018 Mar 6.
• [5] The IHPK1 gene is disrupted at the 3p21.31 breakpoint of t(3;9) in a family with type 2 diabetes mellitus.J Hum Genet. 2004;49(7):360-365. doi: 10.1007/s10038-004-0158-z. Epub 2004 Jun 18.
• [6] Akt activation: A potential strategy to ameliorate insulin resistance.Diabetes Res Clin Pract. 2019 Oct;156:107092. doi: 10.1016/j.diabres.2017.10.004. Epub 2017 Oct 28.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Protein kinase- and lipase inhibitors of inositide metabolism deplete IP(7) indirectly in pancreatic -cells: Off-target effects on cellular bioenergetics and direct effects on IP6K activity. Cell Signal. 2018 Jan;42:127-133. doi: 10.1016/j.cellsig.2017.10.008. Epub 2017 Oct 16.