Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXV8NSR)

• DOT Name: Carbamoyl-phosphate synthase , mitochondrial (CPS1)
• Synonyms: EC 6.3.4.16; Carbamoyl-phosphate synthetase I; CPSase I
• Gene Name: CPS1
• Related Disease: Carbamoyl phosphate synthetase I deficiency disease
• UniProt ID: CPSM_HUMAN
• PDB ID: 2YVQ; 4UTR; 4UTV; 4UTX; 4UTZ; 4UU7; 4UU8; 4UUA; 4UUB; 5DOT; 5DOU; 5OJO; 6UEL; 6W2J
• EC Number: 6.3.4.16
• Pfam ID: PF02786 ; PF02787 ; PF00988 ; PF00117 ; PF02142
• Sequence:
  MTRILTAFKVVRTLKTGFGFTNVTAHQKWKFSRPGIRLLSVKAQTAHIVLEDGTKMKGYS
  FGHPSSVAGEVVFNTGLGGYPEAITDPAYKGQILTMANPIIGNGGAPDTTALDELGLSKY
  LESNGIKVSGLLVLDYSKDYNHWLATKSLGQWLQEEKVPAIYGVDTRMLTKIIRDKGTML
  GKIEFEGQPVDFVDPNKQNLIAEVSTKDVKVYGKGNPTKVVAVDCGIKNNVIRLLVKRGA
  EVHLVPWNHDFTKMEYDGILIAGGPGNPALAEPLIQNVRKILESDRKEPLFGISTGNLIT
  GLAAGAKTYKMSMANRGQNQPVLNITNKQAFITAQNHGYALDNTLPAGWKPLFVNVNDQT
  NEGIMHESKPFFAVQFHPEVTPGPIDTEYLFDSFFSLIKKGKATTITSVLPKPALVASRV
  EVSKVLILGSGGLSIGQAGEFDYSGSQAVKAMKEENVKTVLMNPNIASVQTNEVGLKQAD
  TVYFLPITPQFVTEVIKAEQPDGLILGMGGQTALNCGVELFKRGVLKEYGVKVLGTSVES
  IMATEDRQLFSDKLNEINEKIAPSFAVESIEDALKAADTIGYPVMIRSAYALGGLGSGIC
  PNRETLMDLSTKAFAMTNQILVEKSVTGWKEIEYEVVRDADDNCVTVCNMENVDAMGVHT
  GDSVVVAPAQTLSNAEFQMLRRTSINVVRHLGIVGECNIQFALHPTSMEYCIIEVNARLS
  RSSALASKATGYPLAFIAAKIALGIPLPEIKNVVSGKTSACFEPSLDYMVTKIPRWDLDR
  FHGTSSRIGSSMKSVGEVMAIGRTFEESFQKALRMCHPSIEGFTPRLPMNKEWPSNLDLR
  KELSEPSSTRIYAIAKAIDDNMSLDEIEKLTYIDKWFLYKMRDILNMEKTLKGLNSESMT
  EETLKRAKEIGFSDKQISKCLGLTEAQTRELRLKKNIHPWVKQIDTLAAEYPSVTNYLYV
  TYNGQEHDVNFDDHGMMVLGCGPYHIGSSVEFDWCAVSSIRTLRQLGKKTVVVNCNPETV
  STDFDECDKLYFEELSLERILDIYHQEACGGCIISVGGQIPNNLAVPLYKNGVKIMGTSP
  LQIDRAEDRSIFSAVLDELKVAQAPWKAVNTLNEALEFAKSVDYPCLLRPSYVLSGSAMN
  VVFSEDEMKKFLEEATRVSQEHPVVLTKFVEGAREVEMDAVGKDGRVISHAISEHVEDAG
  VHSGDATLMLPTQTISQGAIEKVKDATRKIAKAFAISGPFNVQFLVKGNDVLVIECNLRA
  SRSFPFVSKTLGVDFIDVATKVMIGENVDEKHLPTLDHPIIPADYVAIKAPMFSWPRLRD
  ADPILRCEMASTGEVACFGEGIHTAFLKAMLSTGFKIPQKGILIGIQQSFRPRFLGVAEQ
  LHNEGFKLFATEATSDWLNANNVPATPVAWPSQEGQNPSLSSIRKLIRDGSIDLVINLPN
  NNTKFVHDNYVIRRTAVDSGIPLLTNFQVTKLFAEAVQKSRKVDSKSLFHYRQYSAGKAA
• Function: Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell.
• Tissue Specificity: Primarily in the liver and small intestine.
• KEGG Pathway:
  Arginine biosynthesis (hsa00220)
  Alanine, aspartate and glutamate metabolism (hsa00250)
  Nitrogen metabolism (hsa00910)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  Biosynthesis of amino acids (hsa01230)
• Reactome Pathway: Urea cycle (R-HSA-70635)
• BioCyc Pathway: MetaCyc:HS00415-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carbamoyl phosphate synthetase I deficiency disease	DISSOMMH	Definitive	Autosomal recessive	[1]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Carbamoyl-phosphate synthase , mitochondrial (CPS1) affects the response to substance of Methotrexate.	[27]
Etoposide	DMNH3PG	Approved	Carbamoyl-phosphate synthase , mitochondrial (CPS1) affects the response to substance of Etoposide.	[27]
Mitomycin	DMH0ZJE	Approved	Carbamoyl-phosphate synthase , mitochondrial (CPS1) affects the response to substance of Mitomycin.	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Nitric Oxide	DM1RBYG	Approved	Carbamoyl-phosphate synthase , mitochondrial (CPS1) affects the abundance of Nitric Oxide.	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[2]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[22]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[10]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[14]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[15]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[16]
Bosentan	DMIOGBU	Approved	Bosentan decreases the expression of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[17]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[21]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[23]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[25]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[26]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Flucloxacillin	DMNUWST	Approved	Flucloxacillin affects the binding of Carbamoyl-phosphate synthase , mitochondrial (CPS1).	[18]

References

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