Details of Drug Off-Target (DOT)

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

• DOT Name: Dipeptidase 2 (DPEP2)
• Synonyms: EC 3.4.13.19
• Gene Name: DPEP2
• Related Disease:
  Alzheimer disease
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
• UniProt ID: DPEP2_HUMAN
• EC Number: 3.4.13.19
• Pfam ID: PF01244
• Sequence:
  MQPSGLEGPGTFGRWPLLSLLLLLLLLQPVTCAYTTPGPPRALTTLGAPRAHTMPGTYAP
  STTLSSPSTQGLQEQARALMRDFPLVDGHNDLPLVLRQVYQKGLQDVNLRNFSYGQTSLD
  RLRDGLVGAQFWSAYVPCQTQDRDALRLTLEQIDLIRRMCASYSELELVTSAKALNDTQK
  LACLIGVEGGHSLDNSLSILRTFYMLGVRYLTLTHTCNTPWAESSAKGVHSFYNNISGLT
  DFGEKVVAEMNRLGMMVDLSHVSDAVARRALEVSQAPVIFSHSAARGVCNSARNVPDDIL
  QLLKKNGGVVMVSLSMGVIQCNPSANVSTVADHFDHIKAVIGSKFIGIGGDYDGAGKFPQ
  GLEDVSTYPVLIEELLSRGWSEEELQGVLRGNLLRVFRQVEKVQEENKWQSPLEDKFPDE
  QLSSSCHSDLSRLRQRQSLTSGQELTEIPIHWTAKLPAKWSVSESSPHMAPVLAVVATFP
  VLILWL
• Function: Dipeptidase that hydrolyzes leukotriene D4 (LTD4) into leukotriene E4 (LTE4). Hydrolyzes cystinyl-bis-glycine ; Independently of its dipeptidase activity can also modulate macrophage inflammatory response by acting as a regulator of NF-kappaB inflammatory signaling pathway.
• Reactome Pathway:
  Aflatoxin activation and detoxification (R-HSA-5423646)
  LTC4-CYSLTR mediated IL4 production (R-HSA-9664535)
  Synthesis of Leukotrienes (LT) and Eoxins (EX) (R-HSA-2142691)
• BioCyc Pathway: MetaCyc:HS09532-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[2]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[2]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Dipeptidase 2 (DPEP2).	[3]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Dipeptidase 2 (DPEP2).	[4]

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 affects the methylation of Dipeptidase 2 (DPEP2).	[5]

References

• [1] Effects of anti-inflammatory and adaptogenic herbal extracts on gene expression of eicosanoids signaling pathways in isolated brain cells.Phytomedicine. 2019 Jul;60:152881. doi: 10.1016/j.phymed.2019.152881. Epub 2019 Mar 10.
• [2] CNDP2 Acts as an Activator for Human Ovarian Cancer Growth and Metastasis via the PI3K/AKT Pathway.Technol Cancer Res Treat. 2019 Jan 1;18:1533033819874773. doi: 10.1177/1533033819874773.
• [3] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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.