Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT80RRQJ)

• DOT Name: CDKN2A-interacting protein (CDKN2AIP)
• Synonyms: Collaborator of ARF
• Gene Name: CDKN2AIP
• Related Disease:
  Advanced cancer
  Neoplasm
• UniProt ID: CARF_HUMAN
• Pfam ID: PF11952
• Sequence:
  MAQEVSEYLSQNPRVAAWVEALRCDGETDKHWRHRRDFLLRNAGDLAPAGGAASASTDEA
  ADAESGTRNRQLQQLISFSMAWANHVFLGCRYPQKVMDKILSMAEGIKVTDAPTYTTRDE
  LVAKVKKRGISSSNEGVEEPSKKRVIEGKNSSAVEQDHAKTSAKTERASAQQENSSTCIG
  SAIKSESGNSARSSGISSQNSSTSDGDRSVSSQSSSSVSSQVTTAGSGKASEAEAPDKHG
  SASFVSLLKSSVNSHMTQSTDSRQQSGSPKKSALEGSSASASQSSSEIEVPLLGSSGSSE
  VELPLLSSKPSSETASSGLTSKTSSEASVSSSVAKNSSSSGTSLLTPKSSSSTNTSLLTS
  KSTSQVAASLLASKSSSQTSGSLVSKSTSLASVSQLASKSSSQTSTSQLPSKSTSQSSES
  SVKFSCKLTNEDVKQKQPFFNRLYKTVAWKLVAVGGFSPNVNHGELLNAAIEALKATLDV
  FFVPLKELADLPQNKSSQESIVCELRCKSVYLGTGCGKSKENAKAVASREALKLFLKKKV
  VVKICKRKYRGSEIEDLVLLDEESRPVNLPPALKHPQELL
• Function: Regulates DNA damage response in a dose-dependent manner through a number of signaling pathways involved in cell proliferation, apoptosis and senescence.
• Tissue Specificity: Ubiquitously expressed.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	CDKN2A-interacting protein (CDKN2AIP) affects the response to substance of Fluorouracil.	[18]

14 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 CDKN2A-interacting protein (CDKN2AIP).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of CDKN2A-interacting protein (CDKN2AIP).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of CDKN2A-interacting protein (CDKN2AIP).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of CDKN2A-interacting protein (CDKN2AIP).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of CDKN2A-interacting protein (CDKN2AIP).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of CDKN2A-interacting protein (CDKN2AIP).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of CDKN2A-interacting protein (CDKN2AIP).	[9]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of CDKN2A-interacting protein (CDKN2AIP).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of CDKN2A-interacting protein (CDKN2AIP).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of CDKN2A-interacting protein (CDKN2AIP).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of CDKN2A-interacting protein (CDKN2AIP).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of CDKN2A-interacting protein (CDKN2AIP).	[15]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of CDKN2A-interacting protein (CDKN2AIP).	[16]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of CDKN2A-interacting protein (CDKN2AIP).	[17]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of CDKN2A-interacting protein (CDKN2AIP).	[13]

References

• [1] Molecular characterization of apoptosis induced by CARF silencing in human cancer cells.Cell Death Differ. 2011 Apr;18(4):589-601. doi: 10.1038/cdd.2010.129. Epub 2010 Nov 5.
• [2] Tumor suppressor activity of miR-451: Identification of CARF as a new target.Sci Rep. 2018 Jan 10;8(1):375. doi: 10.1038/s41598-017-18559-5.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 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.
• [9] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [10] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] 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.
• [13] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [17] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [18] 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.