Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC647SQ)

• DOT Name: Cocaine esterase (CES2)
• Synonyms: EC 3.1.1.84; Carboxylesterase 2; CE-2; hCE-2; EC 3.1.1.1; Methylumbelliferyl-acetate deacetylase 2; EC 3.1.1.56
• Gene Name: CES2
• UniProt ID: EST2_HUMAN
• EC Number: 3.1.1.1; 3.1.1.56; 3.1.1.84
• Pfam ID: PF00135
• Sequence:
  MRLHRLRARLSAVACGLLLLLVRGQGQDSASPIRTTHTGQVLGSLVHVKGANAGVQTFLG
  IPFAKPPLGPLRFAPPEPPESWSGVRDGTTHPAMCLQDLTAVESEFLSQFNMTFPSDSMS
  EDCLYLSIYTPAHSHEGSNLPVMVWIHGGALVFGMASLYDGSMLAALENVVVVIIQYRLG
  VLGFFSTGDKHATGNWGYLDQVAALRWVQQNIAHFGGNPDRVTIFGESAGGTSVSSLVVS
  PISQGLFHGAIMESGVALLPGLIASSADVISTVVANLSACDQVDSEALVGCLRGKSKEEI
  LAINKPFKMIPGVVDGVFLPRHPQELLASADFQPVPSIVGVNNNEFGWLIPKVMRIYDTQ
  KEMDREASQAALQKMLTLLMLPPTFGDLLREEYIGDNGDPQTLQAQFQEMMADSMFVIPA
  LQVAHFQCSRAPVYFYEFQHQPSWLKNIRPPHMKADHGDELPFVFRSFFGGNYIKFTEEE
  EQLSRKMMKYWANFARNGNPNGEGLPHWPLFDQEEQYLQLNLQPAVGRALKAHRLQFWKK
  ALPQKIQELEEPEERHTEL
• Function: Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Shows high catalytic efficiency for hydrolysis of cocaine, 4-methylumbelliferyl acetate, heroin and 6-monoacetylmorphine. Hydrolyzes aspirin, substrates with large alcohol group and small acyl group and endogenous lipids such as triacylglycerol. Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes of 2-arachidonoylglycerol and prostaglandins.
• Tissue Specificity: Preferentially expressed in intestine with moderate expression in liver. Within the intestine, highest expression is found in small intestine with lower expression in colon and rectum.
• KEGG Pathway: Drug metabolism - other enzymes (hsa00983)
• Reactome Pathway:
  Aspirin ADME (R-HSA-9749641)
  Phase I - Functionalization of compounds (R-HSA-211945)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Biotransformations of 11 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Aspirin	DM672AH	Approved	Cocaine esterase (CES2) increases the hydrolysis of Aspirin.	[27]
Permethrin	DMZ0Q1G	Approved	Cocaine esterase (CES2) increases the hydrolysis of Permethrin.	[28]
Morphine	DMRMS0L	Approved	Cocaine esterase (CES2) increases the chemical synthesis of Morphine.	[31]
Heroin diacetylmorphine	DMDBWHY	Approved	Cocaine esterase (CES2) increases the hydrolysis of Heroin diacetylmorphine.	[32]
Procaine	DM4LSNE	Approved	Cocaine esterase (CES2) increases the hydrolysis of Procaine.	[33]
Codeine	DMJX6ZG	Approved	Cocaine esterase (CES2) increases the hydrolysis of Codeine.	[32]
Aniracetam	DMOIFW0	Approved	Cocaine esterase (CES2) increases the hydrolysis of Aniracetam.	[27]
PGF2alpha	DM4XAU7	Clinical trial	Cocaine esterase (CES2) increases the hydrolysis of PGF2alpha.	[34]
Dibutyl phthalate	DMEDGKO	Investigative	Cocaine esterase (CES2) increases the hydrolysis of Dibutyl phthalate.	[35]
2-arachidonoylglycerol	DMM0KOJ	Investigative	Cocaine esterase (CES2) increases the hydrolysis of 2-arachidonoylglycerol.	[34]
Oxybutynine	DMJPBAX	Investigative	Cocaine esterase (CES2) increases the hydrolysis of Oxybutynine.	[27]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	Cocaine esterase (CES2) affects the response to substance of Mitoxantrone.	[29]
Capecitabine	DMTS85L	Approved	Cocaine esterase (CES2) increases the response to substance of Capecitabine.	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Cocaine esterase (CES2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cocaine esterase (CES2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cocaine esterase (CES2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Cocaine esterase (CES2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cocaine esterase (CES2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cocaine esterase (CES2).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Cocaine esterase (CES2).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Cocaine esterase (CES2).	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Cocaine esterase (CES2).	[9]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Cocaine esterase (CES2).	[4]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Cocaine esterase (CES2).	[9]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Cocaine esterase (CES2).	[10]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Cocaine esterase (CES2).	[11]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Cocaine esterase (CES2).	[12]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Cocaine esterase (CES2).	[13]
Cantharidin	DMBP5N3	Approved	Cantharidin decreases the expression of Cocaine esterase (CES2).	[14]
Methoxsalen	DME8FZ9	Approved	Methoxsalen increases the expression of Cocaine esterase (CES2).	[13]
Tacrine	DM51FY6	Approved	Tacrine decreases the activity of Cocaine esterase (CES2).	[15]
Rivastigmine	DMG629M	Approved	Rivastigmine decreases the activity of Cocaine esterase (CES2).	[15]
Galantamine	DMEO794	Approved	Galantamine decreases the activity of Cocaine esterase (CES2).	[15]
Ibrolipim	DMOPWSX	Phase 2	Ibrolipim increases the expression of Cocaine esterase (CES2).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cocaine esterase (CES2).	[19]
Physostigmine	DM2N0TO	Discontinued in Phase 2	Physostigmine decreases the activity of Cocaine esterase (CES2).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cocaine esterase (CES2).	[21]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal increases the activity of Cocaine esterase (CES2).	[22]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos decreases the activity of Cocaine esterase (CES2).	[23]
Paraoxon	DMN4ZKC	Investigative	Paraoxon decreases the activity of Cocaine esterase (CES2).	[24]
Sanggenon C	DMSF5DW	Investigative	Sanggenon C decreases the activity of Cocaine esterase (CES2).	[25]
Org-231295	DMTFGYH	Investigative	Org-231295 decreases the activity of Cocaine esterase (CES2).	[26]
S 3025	DMZN0RW	Investigative	S 3025 decreases the activity of Cocaine esterase (CES2).	[24]
TOLSERINE	DMPTM6V	Investigative	TOLSERINE decreases the activity of Cocaine esterase (CES2).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Dextropropoxyphene	DM23HCX	Approved	Dextropropoxyphene affects the binding of Cocaine esterase (CES2).	[16]

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 Cocaine esterase (CES2).	[18]

References

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