Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKXKUT8)

• DOT Name: Protein NipSnap homolog 1 (NIPSNAP1)
• Synonyms: NipSnap1
• Gene Name: NIPSNAP1
• Related Disease:
  Neoplasm
  Prostate cancer
  Prostate carcinoma
• UniProt ID: NIPS1_HUMAN
• Pfam ID: PF07978
• Sequence:
  MAPRLCSISVTARRLLGGPGPRAGDVASAAAARFYSKDNEGSWFRSLFVHKVDPRKDAHS
  TLLSKKETSNLYKIQFHNVKPEYLDAYNSLTEAVLPKLHLDEDYPCSLVGNWNTWYGEQD
  QAVHLWRFSGGYPALMDCMNKLKNNKEYLEFRRERSQMLLSRRNQLLLEFSFWNEPQPRM
  GPNIYELRTYKLKPGTMIEWGNNWARAIKYRQENQEAVGGFFSQIGELYVVHHLWAYKDL
  QSREETRNAAWRKRGWDENVYYTVPLVRHMESRIMIPLKISPLQ
• Tissue Specificity: Ubiquitous. Highest expression in liver.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	moderate	Biomarker	[1]
Prostate cancer	DISF190Y	moderate	Biomarker	[1]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Protein NipSnap homolog 1 (NIPSNAP1).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Protein NipSnap homolog 1 (NIPSNAP1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein NipSnap homolog 1 (NIPSNAP1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein NipSnap homolog 1 (NIPSNAP1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein NipSnap homolog 1 (NIPSNAP1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein NipSnap homolog 1 (NIPSNAP1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein NipSnap homolog 1 (NIPSNAP1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein NipSnap homolog 1 (NIPSNAP1).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Protein NipSnap homolog 1 (NIPSNAP1).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Protein NipSnap homolog 1 (NIPSNAP1).	[11]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Protein NipSnap homolog 1 (NIPSNAP1).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein NipSnap homolog 1 (NIPSNAP1).	[13]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Protein NipSnap homolog 1 (NIPSNAP1).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein NipSnap homolog 1 (NIPSNAP1).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein NipSnap homolog 1 (NIPSNAP1).	[16]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Protein NipSnap homolog 1 (NIPSNAP1).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein NipSnap homolog 1 (NIPSNAP1).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein NipSnap homolog 1 (NIPSNAP1).	[19]

References

• [1] Chromosomal structural variations during progression of a prostate epithelial cell line to a malignant metastatic state inactivate the NF2, NIPSNAP1, UGT2B17, and LPIN2 genes.Cancer Biol Ther. 2013 Sep;14(9):840-52. doi: 10.4161/cbt.25329. Epub 2013 Jul 26.
• [2] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [3] 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.
• [4] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [5] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [10] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [11] Gene induction and apoptosis in human hepatocellular carci-noma cells SMMC-7721 exposed to 5-aza-2'-deoxycytidine. Chin Med J (Engl). 2007 Sep 20;120(18):1626-31.
• [12] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [15] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [16] 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.
• [17] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [18] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [19] 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.