Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3UQXXV)

• DOT Name: Aspartyl aminopeptidase (DNPEP)
• Synonyms: EC 3.4.11.21
• Gene Name: DNPEP
• UniProt ID: DNPEP_HUMAN
• PDB ID: 4DYO
• EC Number: 3.4.11.21
• Pfam ID: PF02127
• Sequence:
  MSGHSPTRGAMQVAMNGKARKEAVQTAAKELLKFVNRSPSPFHAVAECRNRLLQAGFSEL
  KETEKWNIKPESKYFMTRNSSTIIAFAVGGQYVPGNGFSLIGAHTDSPCLRVKRRSRRSQ
  VGFQQVGVETYGGGIWSTWFDRDLTLAGRVIVKCPTSGRLEQQLVHVERPILRIPHLAIH
  LQRNINENFGPNTEMHLVPILATAIQEELEKGTPEPGPLNAVDERHHSVLMSLLCAHLGL
  SPKDIVEMELCLADTQPAVLGGAYDEFIFAPRLDNLHSCFCALQALIDSCAGPGSLATEP
  HVRMVTLYDNEEVGSESAQGAQSLLTELVLRRISASCQHPTAFEEAIPKSFMISADMAHA
  VHPNYLDKHEENHRPLFHKGPVIKVNSKQRYASNAVSEALIREVANKVKVPLQDLMVRND
  TPCGTTIGPILASRLGLRVLDLGSPQLAMHSIREMACTTGVLQTLTLFKGFFELFPSLSH
  NLLVD
• Function: Aminopeptidase with specificity towards an acidic amino acid at the N-terminus. Likely to play an important role in intracellular protein and peptide metabolism.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

8 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 Aspartyl aminopeptidase (DNPEP).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Aspartyl aminopeptidase (DNPEP).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Aspartyl aminopeptidase (DNPEP).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Aspartyl aminopeptidase (DNPEP).	[4]
Selenium	DM25CGV	Approved	Selenium increases the expression of Aspartyl aminopeptidase (DNPEP).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Aspartyl aminopeptidase (DNPEP).	[6]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Aspartyl aminopeptidase (DNPEP).	[7]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Aspartyl aminopeptidase (DNPEP).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Aspartyl aminopeptidase (DNPEP).	[8]

References

• [1] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [8] 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.
• [9] Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway. J Biochem Mol Toxicol. 2010 Mar-Apr;24(2):73-88.