Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9L0LR8)

• DOT Name: Liver carboxylesterase 1 (CES1)
• Synonyms: Acyl-coenzyme A:cholesterol acyltransferase; ACAT; Brain carboxylesterase hBr1; Carboxylesterase 1; CE-1; hCE-1; EC 3.1.1.1; Cholesteryl ester hydrolase; CEH; EC 3.1.1.13; Cocaine carboxylesterase; Egasyn; HMSE; Methylumbelliferyl-acetate deacetylase 1; EC 3.1.1.56; Monocyte/macrophage serine esterase; Retinyl ester hydrolase; REH; Serine esterase 1; Triacylglycerol hydrolase; TGH
• Gene Name: CES1
• UniProt ID: EST1_HUMAN
• PDB ID: 1MX1; 1MX5; 1MX9; 1YA4; 1YA8; 1YAH; 1YAJ; 2DQY; 2DQZ; 2DR0; 2H7C; 2HRQ; 2HRR; 3K9B; 4AB1; 5A7F; 5A7G; 5A7H; 8EOR
• EC Number: 3.1.1.1; 3.1.1.13; 3.1.1.56
• Pfam ID: PF00135
• Sequence:
  MWLRAFILATLSASAAWGHPSSPPVVDTVHGKVLGKFVSLEGFAQPVAIFLGIPFAKPPL
  GPLRFTPPQPAEPWSFVKNATSYPPMCTQDPKAGQLLSELFTNRKENIPLKLSEDCLYLN
  IYTPADLTKKNRLPVMVWIHGGGLMVGAASTYDGLALAAHENVVVVTIQYRLGIWGFFST
  GDEHSRGNWGHLDQVAALRWVQDNIASFGGNPGSVTIFGESAGGESVSVLVLSPLAKNLF
  HRAISESGVALTSVLVKKGDVKPLAEQIAITAGCKTTTSAVMVHCLRQKTEEELLETTLK
  MKFLSLDLQGDPRESQPLLGTVIDGMLLLKTPEELQAERNFHTVPYMVGINKQEFGWLIP
  MQLMSYPLSEGQLDQKTAMSLLWKSYPLVCIAKELIPEATEKYLGGTDDTVKKKDLFLDL
  IADVMFGVPSVIVARNHRDAGAPTYMYEFQYRPSFSSDMKPKTVIGDHGDELFSVFGAPF
  LKEGASEEEIRLSKMVMKFWANFARNGNPNGEGLPHWPEYNQKEGYLQIGANTQAAQKLK
  DKEVAFWTNLFAKKAVEKPPQTEHIEL
• Function: Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester. Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine. Catalyzes the transesterification of cocaine to form cocaethylene. Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate. Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes of 2-arachidonoylglycerol and prostaglandins. Hydrolyzes cellular cholesteryl esters to free cholesterols and promotes reverse cholesterol transport (RCT) by facilitating both the initial and final steps in the process. First of all, allows free cholesterol efflux from macrophages to extracellular cholesterol acceptors and secondly, releases free cholesterol from lipoprotein-delivered cholesteryl esters in the liver for bile acid synthesis or direct secretion into the bile.
• Tissue Specificity: Expressed predominantly in liver with lower levels in heart and lung . Expressed in macrophages .
• KEGG Pathway: Drug metabolism - other enzymes (hsa00983)
• Reactome Pathway:
  Phase I - Functionalization of compounds (R-HSA-211945)
  Physiological factors (R-HSA-5578768)
  Aspirin ADME (R-HSA-9749641)
  Metabolism of Angiotensinogen to Angiotensins (R-HSA-2022377)
• BioCyc Pathway: MetaCyc:HS11616-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Liver carboxylesterase 1 (CES1) increases the abundance of Decitabine.	[37]
Felbamate	DM1V5ZS	Approved	Liver carboxylesterase 1 (CES1) increases the metabolism of Felbamate.	[44]
Oseltamivir	DMGO72P	Approved	Liver carboxylesterase 1 (CES1) increases the metabolism of Oseltamivir.	[45]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Irinotecan	DMP6SC2	Approved	Liver carboxylesterase 1 (CES1) increases the response to substance of Irinotecan.	[38]
Simvastatin	DM30SGU	Approved	Liver carboxylesterase 1 (CES1) increases the Arteriosclerosis ADR of Simvastatin.	[41]
Pravastatin	DM6A0X7	Approved	Liver carboxylesterase 1 (CES1) increases the Arteriosclerosis ADR of Pravastatin.	[41]
Fluvastatin	DM4MDJY	Approved	Liver carboxylesterase 1 (CES1) increases the Arteriosclerosis ADR of Fluvastatin.	[41]
Atorvastatin	DMF28YC	Phase 3 Trial	Liver carboxylesterase 1 (CES1) increases the Arteriosclerosis ADR of Atorvastatin.	[41]

This DOT Affected the Biotransformations of 12 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Permethrin	DMZ0Q1G	Approved	Liver carboxylesterase 1 (CES1) increases the hydrolysis of Permethrin.	[39]
Cocaine	DMSOX7I	Approved	Liver carboxylesterase 1 (CES1) increases the hydrolysis of Cocaine.	[40]
Heroin diacetylmorphine	DMDBWHY	Approved	Liver carboxylesterase 1 (CES1) decreases the acetylation of Heroin diacetylmorphine.	[42]
Ramipril	DM2R68E	Approved	Liver carboxylesterase 1 (CES1) increases the hydrolysis of Ramipril.	[43]
Aniracetam	DMOIFW0	Approved	Liver carboxylesterase 1 (CES1) increases the hydrolysis of Aniracetam.	[46]
Temocapril hydrochloride	DM0JXFL	Approved	Liver carboxylesterase 1 (CES1) increases the hydrolysis of Temocapril hydrochloride.	[47]
Temocaprilate	DMNX2QI	Approved	Liver carboxylesterase 1 (CES1) increases the chemical synthesis of Temocaprilate.	[47]
Remdesivir	DMBFZ6L	Phase 3 Trial	Liver carboxylesterase 1 (CES1) increases the hydrolysis of Remdesivir.	[48]
PGF2alpha	DM4XAU7	Clinical trial	Liver carboxylesterase 1 (CES1) increases the hydrolysis of PGF2alpha.	[49]
Dibutyl phthalate	DMEDGKO	Investigative	Liver carboxylesterase 1 (CES1) increases the hydrolysis of Dibutyl phthalate.	[50]
Mononitrophenol	DM4QO9G	Investigative	Liver carboxylesterase 1 (CES1) increases the chemical synthesis of Mononitrophenol.	[51]
2-arachidonoylglycerol	DMM0KOJ	Investigative	Liver carboxylesterase 1 (CES1) increases the hydrolysis of 2-arachidonoylglycerol.	[49]

2 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 Liver carboxylesterase 1 (CES1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Liver carboxylesterase 1 (CES1).	[25]

44 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 Liver carboxylesterase 1 (CES1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Liver carboxylesterase 1 (CES1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Liver carboxylesterase 1 (CES1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Liver carboxylesterase 1 (CES1).	[5]
Selenium	DM25CGV	Approved	Selenium increases the expression of Liver carboxylesterase 1 (CES1).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Liver carboxylesterase 1 (CES1).	[7]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Liver carboxylesterase 1 (CES1).	[8]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Liver carboxylesterase 1 (CES1).	[9]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Liver carboxylesterase 1 (CES1).	[10]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Liver carboxylesterase 1 (CES1).	[11]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Liver carboxylesterase 1 (CES1).	[12]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Liver carboxylesterase 1 (CES1).	[7]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Liver carboxylesterase 1 (CES1).	[11]
Ampicillin	DMHWE7P	Approved	Ampicillin increases the expression of Liver carboxylesterase 1 (CES1).	[13]
Cantharidin	DMBP5N3	Approved	Cantharidin affects the expression of Liver carboxylesterase 1 (CES1).	[14]
Tacrine	DM51FY6	Approved	Tacrine decreases the activity of Liver carboxylesterase 1 (CES1).	[16]
Rivastigmine	DMG629M	Approved	Rivastigmine decreases the activity of Liver carboxylesterase 1 (CES1).	[18]
Penicillin V	DMKVOYF	Approved	Penicillin V increases the expression of Liver carboxylesterase 1 (CES1).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Liver carboxylesterase 1 (CES1).	[20]
Benzylpenicillin	DMS9503	Phase 3	Benzylpenicillin increases the expression of Liver carboxylesterase 1 (CES1).	[13]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Liver carboxylesterase 1 (CES1).	[2]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Liver carboxylesterase 1 (CES1).	[6]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Liver carboxylesterase 1 (CES1).	[21]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin increases the expression of Liver carboxylesterase 1 (CES1).	[22]
ANW-32821	DMMJOZD	Phase 2	ANW-32821 increases the expression of Liver carboxylesterase 1 (CES1).	[23]
Ibrolipim	DMOPWSX	Phase 2	Ibrolipim increases the expression of Liver carboxylesterase 1 (CES1).	[24]
PIRINIXIC ACID	DM82Y75	Preclinical	PIRINIXIC ACID decreases the expression of Liver carboxylesterase 1 (CES1).	[26]
Ciglitazone	DMAPO0T	Preclinical	Ciglitazone decreases the expression of Liver carboxylesterase 1 (CES1).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Liver carboxylesterase 1 (CES1).	[27]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Liver carboxylesterase 1 (CES1).	[28]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Liver carboxylesterase 1 (CES1).	[29]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the activity of Liver carboxylesterase 1 (CES1).	[30]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Liver carboxylesterase 1 (CES1).	[21]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos decreases the activity of Liver carboxylesterase 1 (CES1).	[31]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid decreases the activity of Liver carboxylesterase 1 (CES1).	[32]
2-tert-butylbenzene-1,4-diol	DMNXI1E	Investigative	2-tert-butylbenzene-1,4-diol increases the expression of Liver carboxylesterase 1 (CES1).	[33]
Paraoxon	DMN4ZKC	Investigative	Paraoxon decreases the activity of Liver carboxylesterase 1 (CES1).	[34]
27-hydroxycholesterol	DM2L6OZ	Investigative	27-hydroxycholesterol decreases the activity of Liver carboxylesterase 1 (CES1).	[32]
Chlorphrifos oxon	DMGBT68	Investigative	Chlorphrifos oxon decreases the activity of Liver carboxylesterase 1 (CES1).	[35]
PGJ2	DMR2LTC	Investigative	PGJ2 decreases the expression of Liver carboxylesterase 1 (CES1).	[26]
Org-231295	DMTFGYH	Investigative	Org-231295 decreases the activity of Liver carboxylesterase 1 (CES1).	[36]
S 3025	DMZN0RW	Investigative	S 3025 decreases the activity of Liver carboxylesterase 1 (CES1).	[34]
TOLSERINE	DMPTM6V	Investigative	TOLSERINE decreases the activity of Liver carboxylesterase 1 (CES1).	[18]
eicosatetranoic acid	DMAKP20	Investigative	eicosatetranoic acid decreases the expression of Liver carboxylesterase 1 (CES1).	[26]

3 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 Liver carboxylesterase 1 (CES1).	[15]
Naloxone	DM3FXMA	Approved	Naloxone affects the binding of Liver carboxylesterase 1 (CES1).	[17]
Dextropropoxyphene	DM23HCX	Approved	Dextropropoxyphene affects the binding of Liver carboxylesterase 1 (CES1).	[19]

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