Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMJF2RB)

• DOT Name: Probable aminopeptidase NPEPL1 (NPEPL1)
• Synonyms: EC 3.4.11.-; Aminopeptidase-like 1
• Gene Name: NPEPL1
• UniProt ID: PEPL1_HUMAN
• EC Number: 3.4.11.-
• Pfam ID: PF18295 ; PF00883
• Sequence:
  MANVGLQFQASAGDSDPQSRPLLLLGQLHHLHRVPWSHVRGKLQPRVTEELWQAALSTLN
  PNPTDSCPLYLNYATVAALPCRVSRHNSPSAAHFITRLVRTCLPPGAHRCIVMVCEQPEV
  FASACALARAFPLFTHRSGASRRLEKKTVTVEFFLVGQDNGPVEVSTLQCLANATDGVRL
  AARIVDTPCNEMNTDTFLEEINKVGKELGIIPTIIRDEELKTRGFGGIYGVGKAALHPPA
  LAVLSHTPDGATQTIAWVGKGIVYDTGGLSIKGKTTMPGMKRDCGGAAAVLGAFRAAIKQ
  GFKDNLHAVFCLAENSVGPNATRPDDIHLLYSGKTVEINNTDAEGRLVLADGVSYACKDL
  GADIILDMATLTGAQGIATGKYHAAVLTNSAEWEAACVKAGRKCGDLVHPLVYCPELHFS
  EFTSAVADMKNSVADRDNSPSSCAGLFIASHIGFDWPGVWVHLDIAAPVHAGERATGFGV
  ALLLALFGRASEDPLLNLVSPLGCEVDVEEGDLGRDSKRRRLV
• Function: Probably catalyzes the removal of unsubstituted N-terminal amino acids from various peptides.
• Tissue Specificity: Ubiquitously expressed.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Probable aminopeptidase NPEPL1 (NPEPL1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Probable aminopeptidase NPEPL1 (NPEPL1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Probable aminopeptidase NPEPL1 (NPEPL1).	[2]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Probable aminopeptidase NPEPL1 (NPEPL1).	[3]
Selenium	DM25CGV	Approved	Selenium increases the expression of Probable aminopeptidase NPEPL1 (NPEPL1).	[4]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Probable aminopeptidase NPEPL1 (NPEPL1).	[4]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Probable aminopeptidase NPEPL1 (NPEPL1).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Probable aminopeptidase NPEPL1 (NPEPL1).	[7]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Probable aminopeptidase NPEPL1 (NPEPL1).	[8]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [7] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [8] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.