Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCGBS3H)

• DOT Name: Actin-binding protein IPP (IPP)
• Synonyms: Intracisternal A particle-promoted polypeptide; IPP; Kelch-like protein 27
• Gene Name: IPP
• Related Disease:
  Colorectal carcinoma
  Colorectal neoplasm
  Precocious puberty
  Bone disease
  Colon cancer
  Colon carcinoma
  Epithelial neoplasm
  Myocardial infarction
  Keratitis
  Plasma cell myeloma
• UniProt ID: IPP_HUMAN
• Pfam ID: PF07707 ; PF00651 ; PF01344
• Sequence:
  MANEDCPKAADSPFSSDKHAQLILAQINKMRNGQHFCDVQLQVGQESFKAHRLVLAASSP
  YFAALFTGGMKESSKDVVPILGIEAGIFQILLDFIYTGIVNIGVNNVQELIIAADMLQLT
  EVVHLCCEFLKGQIDPLNCIGIFQFSEQIACHDLLEFSENYIHVHFLEVHSGEEFLALTK
  DQLIKILRSEELSIEDEYQVFLAAMQWILKDLGKRRKHVVEVLDPIRFPLLPPQRLLKYI
  EGVSDFNLRVALQTLLKEYCEVCKSPKENKFCSFLQTSKVRPRKKARKYLYAVGGYTRLQ
  GGRWSDSRALSCVERFDTFSQYWTTVSSLHQARSGLGVTVLGGMVYAIGGEKDSMIFDCT
  ECYDPVTKQWTTVASMNHPRCGLGVCVCYGAIYALGGWVGAEIGNTIERFDPDENKWEVV
  GNMAVSRYYFGCCEMQGLIYVIGGISNEGIELRSFEVYDPLSKRWSPLPPMGTRRAYLGV
  AALNDCIYSVGGWNETQDALHTVEKYSFEEEKWVEVASMKVPRAGMCVVAVNGLLYVSGG
  RSSSHDFLAPGTLDSVEVYNPHSDTWTEIGNMITSRCEGGVAVL
• Function: May play a role in organizing the actin cytoskeleton.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Definitive	Biomarker	[1]
Colorectal neoplasm	DISR1UCN	Definitive	Biomarker	[1]
Precocious puberty	DISYI2XZ	Definitive	Biomarker	[2]
Bone disease	DISE1F82	Strong	Biomarker	[3]
Colon cancer	DISVC52G	Strong	Biomarker	[4]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[4]
Epithelial neoplasm	DIS0T594	Strong	Biomarker	[5]
Myocardial infarction	DIS655KI	Strong	Biomarker	[6]
Keratitis	DISMFOEI	moderate	Biomarker	[7]
Plasma cell myeloma	DIS0DFZ0	Limited	Biomarker	[8]

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 Actin-binding protein IPP (IPP).	[9]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Actin-binding protein IPP (IPP).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Actin-binding protein IPP (IPP).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Actin-binding protein IPP (IPP).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Actin-binding protein IPP (IPP).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Actin-binding protein IPP (IPP).	[14]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Actin-binding protein IPP (IPP).	[15]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Actin-binding protein IPP (IPP).	[16]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Actin-binding protein IPP (IPP).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Actin-binding protein IPP (IPP).	[18]

References

• [1] Highly Expressed Genes in Rapidly Proliferating Tumor Cells as New Targets for Colorectal Cancer Treatment.Clin Cancer Res. 2015 Aug 15;21(16):3695-704. doi: 10.1158/1078-0432.CCR-14-2457. Epub 2015 May 5.
• [2] Improved final predicted height with the injection of leuprolide in children with earlier puberty: A retrospective cohort study.PLoS One. 2017 Oct 3;12(10):e0185080. doi: 10.1371/journal.pone.0185080. eCollection 2017.
• [3] Macrophage migration inhibitory factor (MIF) inhibitor 4-IPP suppresses osteoclast formation and promotes osteoblast differentiation through the inhibition of the NF-B signaling pathway.FASEB J. 2019 Jun;33(6):7667-7683. doi: 10.1096/fj.201802364RR. Epub 2019 Mar 20.
• [4] PINCH-2 presents functional copy number variation and suppresses migration of colon cancer cells by paracrine activity.Int J Cancer. 2015 May 15;136(10):2273-83. doi: 10.1002/ijc.29273. Epub 2014 Oct 30.
• [5] Quantitative chemical proteomics profiling differentiates erlotinib from gefitinib in EGFR wild-type non-small cell lung carcinoma cell lines.Mol Cancer Ther. 2013 Apr;12(4):520-9. doi: 10.1158/1535-7163.MCT-12-0880. Epub 2013 Jan 31.
• [6] Long-Term Risk Factor Control After Myocardial Infarction-A Need for Better Prevention Programmes.J Clin Med. 2019 Jul 27;8(8):1114. doi: 10.3390/jcm8081114.
• [7] Expression of macrophage migration inhibitory factor in Aspergillus fumigatus keratitis.Int J Ophthalmol. 2019 May 18;12(5):711-716. doi: 10.18240/ijo.2019.05.03. eCollection 2019.
• [8] Macrophage Inhibitory Factor-1 (MIF-1) controls the plasticity of multiple myeloma tumor cells.PLoS One. 2018 Nov 1;13(11):e0206368. doi: 10.1371/journal.pone.0206368. eCollection 2018.
• [9] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [10] 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.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [13] 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.
• [14] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [17] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [18] 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.