Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5SP1KJ)

• DOT Name: AMP deaminase 3 (AMPD3)
• Synonyms: EC 3.5.4.6; AMP deaminase isoform E; Erythrocyte AMP deaminase
• Gene Name: AMPD3
• Related Disease:
  Neoplasm
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Depression
  Epithelial ovarian cancer
  Glycogen storage disease VII
  Ovarian cancer
  Ovarian neoplasm
  Bipolar disorder
  Gastrointestinal stromal tumour
  Major depressive disorder
  Mental disorder
  Psychotic disorder
  Adenosine monophosphate deaminase deficiency
• UniProt ID: AMPD3_HUMAN
• EC Number: 3.5.4.6
• Pfam ID: PF19326
• Sequence:
  MPRQFPKLNISEVDEQVRLLAEKVFAKVLREEDSKDALSLFTVPEDCPIGQKEAKERELQ
  KELAEQKSVETAKRKKSFKMIRSQSLSLQMPPQQDWKGPPAASPAMSPTTPVVTGATSLP
  TPAPYAMPEFQRVTISGDYCAGITLEDYEQAAKSLAKALMIREKYARLAYHRFPRITSQY
  LGHPRADTAPPEEGLPDFHPPPLPQEDPYCLDDAPPNLDYLVHMQGGILFVYDNKKMLEH
  QEPHSLPYPDLETYTVDMSHILALITDGPTKTYCHRRLNFLESKFSLHEMLNEMSEFKEL
  KSNPHRDFYNVRKVDTHIHAAACMNQKHLLRFIKHTYQTEPDRTVAEKRGRKITLRQVFD
  GLHMDPYDLTVDSLDVHAGRQTFHRFDKFNSKYNPVGASELRDLYLKTENYLGGEYFARM
  VKEVARELEESKYQYSEPRLSIYGRSPEEWPNLAYWFIQHKVYSPNMRWIIQVPRIYDIF
  RSKKLLPNFGKMLENIFLPLFKATINPQDHRELHLFLKYVTGFDSVDDESKHSDHMFSDK
  SPNPDVWTSEQNPPYSYYLYYMYANIMVLNNLRRERGLSTFLFRPHCGEAGSITHLVSAF
  LTADNISHGLLLKKSPVLQYLYYLAQIPIAMSPLSNNSLFLEYSKNPLREFLHKGLHVSL
  STDDPMQFHYTKEALMEEYAIAAQVWKLSTCDLCEIARNSVLQSGLSHQEKQKFLGQNYY
  KEGPEGNDIRKTNVAQIRMAFRYETLCNELSFLSDAMKSEEITALTN
• Function: AMP deaminase plays a critical role in energy metabolism.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
  Cytoskeleton in muscle cells (hsa04820)
• Reactome Pathway:
  Purine salvage (R-HSA-74217)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Colon cancer	DISVC52G	Strong	Biomarker	[2]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[2]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[2]
Depression	DIS3XJ69	Strong	Altered Expression	[3]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[4]
Glycogen storage disease VII	DISWZUF2	Strong	Biomarker	[5]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[4]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[4]
Bipolar disorder	DISAM7J2	moderate	Genetic Variation	[6]
Gastrointestinal stromal tumour	DIS6TJYS	moderate	Biomarker	[7]
Major depressive disorder	DIS4CL3X	moderate	Genetic Variation	[6]
Mental disorder	DIS3J5R8	moderate	Genetic Variation	[6]
Psychotic disorder	DIS4UQOT	moderate	Genetic Variation	[6]
Adenosine monophosphate deaminase deficiency	DISY0LK9	Supportive	Autosomal recessive	[8]

3 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 AMP deaminase 3 (AMPD3).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of AMP deaminase 3 (AMPD3).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of AMP deaminase 3 (AMPD3).	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of AMP deaminase 3 (AMPD3).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of AMP deaminase 3 (AMPD3).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of AMP deaminase 3 (AMPD3).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of AMP deaminase 3 (AMPD3).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of AMP deaminase 3 (AMPD3).	[14]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of AMP deaminase 3 (AMPD3).	[15]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of AMP deaminase 3 (AMPD3).	[16]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of AMP deaminase 3 (AMPD3).	[17]
Selenium	DM25CGV	Approved	Selenium decreases the expression of AMP deaminase 3 (AMPD3).	[18]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of AMP deaminase 3 (AMPD3).	[19]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate increases the expression of AMP deaminase 3 (AMPD3).	[20]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of AMP deaminase 3 (AMPD3).	[21]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of AMP deaminase 3 (AMPD3).	[17]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of AMP deaminase 3 (AMPD3).	[24]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of AMP deaminase 3 (AMPD3).	[25]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of AMP deaminase 3 (AMPD3).	[24]
acrolein	DMAMCSR	Investigative	acrolein increases the expression of AMP deaminase 3 (AMPD3).	[24]
1,6-hexamethylene diisocyanate	DMLB3RT	Investigative	1,6-hexamethylene diisocyanate increases the expression of AMP deaminase 3 (AMPD3).	[24]
NSC-1771	DMNXDGQ	Investigative	NSC-1771 increases the expression of AMP deaminase 3 (AMPD3).	[24]

References

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• [21] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [22] 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.
• [23] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [24] Gene expressions changes in bronchial epithelial cells: markers for respiratory sensitizers and exploration of the NRF2 pathway. Toxicol In Vitro. 2014 Mar;28(2):209-17.
• [25] Primary Human Hepatocyte Spheroids as Tools to Study the Hepatotoxic Potential of Non-Pharmaceutical Chemicals. Int J Mol Sci. 2021 Oct 12;22(20):11005. doi: 10.3390/ijms222011005.