Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3HXP6N)

• DOT Name: Cytidine deaminase (CDA)
• Synonyms: EC 3.5.4.5; Cytidine aminohydrolase
• Gene Name: CDA
• UniProt ID: CDD_HUMAN
• PDB ID: 1MQ0
• EC Number: 3.5.4.5
• Pfam ID: PF00383
• Sequence:
  MAQKRPACTLKPECVQQLLVCSQEAKKSAYCPYSHFPVGAALLTQEGRIFKGCNIENACY
  PLGICAERTAIQKAVSEGYKDFRAIAIASDMQDDFISPCGACRQVMREFGTNWPVYMTKP
  DGTYIVMTVQELLPSSFGPEDLQKTQ
• Function: This enzyme scavenges exogenous and endogenous cytidine and 2'-deoxycytidine for UMP synthesis.
• Tissue Specificity: Highly expressed in granulocytes while expression is very low in fibroblasts, chondrocytes, monocytes, and T- as well as B-cell lines.
• KEGG Pathway:
  Pyrimidine metabolism (hsa00240)
  Drug metabolism - other enzymes (hsa00983)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
• Reactome Pathway:
  Pyrimidine salvage (R-HSA-73614)
  Neutrophil degranulation (R-HSA-6798695)
• BioCyc Pathway: MetaCyc:HS08334-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Cytidine deaminase (CDA) increases the degradation of Decitabine.	[21]

This DOT Affected the Drug Response of 5 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Cytidine deaminase (CDA) affects the response to substance of Paclitaxel.	[22]
Gemcitabine	DMSE3I7	Approved	Cytidine deaminase (CDA) affects the response to substance of Gemcitabine.	[22]
Melphalan	DMOLNHF	Approved	Cytidine deaminase (CDA) decreases the response to substance of Melphalan.	[23]
Chlorambucil	DMRKE63	Approved	Cytidine deaminase (CDA) decreases the response to substance of Chlorambucil.	[23]
Tegafur	DM31ZQM	Approved	Cytidine deaminase (CDA) affects the response to substance of Tegafur.	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Cytidine deaminase (CDA).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cytidine deaminase (CDA).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cytidine deaminase (CDA).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cytidine deaminase (CDA).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Cytidine deaminase (CDA).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cytidine deaminase (CDA).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Cytidine deaminase (CDA).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Cytidine deaminase (CDA).	[8]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Cytidine deaminase (CDA).	[9]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol increases the expression of Cytidine deaminase (CDA).	[10]
Crizotinib	DM4F29C	Approved	Crizotinib decreases the expression of Cytidine deaminase (CDA).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cytidine deaminase (CDA).	[12]
Tetrahydrouridine	DMR5GSB	Phase 2	Tetrahydrouridine decreases the activity of Cytidine deaminase (CDA).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cytidine deaminase (CDA).	[15]
Celastrol	DMWQIJX	Preclinical	Celastrol increases the expression of Cytidine deaminase (CDA).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Cytidine deaminase (CDA).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Cytidine deaminase (CDA).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Cytidine deaminase (CDA).	[19]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Cytidine deaminase (CDA).	[20]

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 increases the methylation of Cytidine deaminase (CDA).	[14]

References

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• [10] Dihydropyrimidine dehydrogenases and cytidine-deaminase gene polymorphisms as outcome predictors in resected gastric cancer patients treated with fluoropyrimidine adjuvant chemotherapy. J Surg Oncol. 2008 Aug 1;98(2):130-4.
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• [23] Coexpression of rat glutathione S-transferase A3 and human cytidine deaminase by a bicistronic retroviral vector confers in vitro resistance to nitrogen mustards and cytosine arabinoside in murine fibroblasts. Cancer Gene Ther. 2000 May;7(5):757-65. doi: 10.1038/sj.cgt.7700169.