Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTMF541)

• DTT Name: Liver carboxylesterase (CES1)
• Synonyms: Serine esterase 1; Monocyte/macrophage serine esterase; Human carboxylesterase 1; HMSE; HCE1; CES1; Brain carboxylesterase hBr1; Acyl coenzyme A:cholesterol acyltransferase
• Gene Name: CES1
• DTT Type: Successful target; [1]
• BioChemical Class: Carboxylic ester hydrolase
• UniProt ID: EST1_HUMAN
• TTD ID: T76369
• EC Number: EC 3.1.1.1
• 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.
• KEGG Pathway:
  Drug metabolism - other enzymes (hsa00983)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Phase I - Functionalization of compounds (R-HSA-211945)
  Aspirin ADME (R-HSA-9749641)
  Metabolism of Angiotensinogen to Angiotensins (R-HSA-2022377)
• BioCyc Pathway: MetaCyc:HS11616-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cholic Acid	DM7OKQV	Cholelithiasis	DC11	Approved	[1]

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PACTIMIBE	DM0NZDT	Arteriosclerosis	BD40	Phase 2/3	[2]
Eldacimibe	DML7WP0	Hyperlipidaemia	5C80	Phase 2	[3]
K-604	DMQVN6P	Arteriosclerosis	BD40	Phase 2	[4]
GR148672X	DM7W6YN	Acute lymphoblastic leukaemia	2A85	Clinical trial	[5]

21 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Avasimibe	DMFG4OM	Peripheral vascular disease	BD4Z	Discontinued in Phase 3	[6]
CI-976	DMBO28J	Hyperlipidaemia	5C80	Discontinued in Phase 2	[7]
CL-283796	DM7LIDT	Hyperlipidaemia	5C80	Discontinued in Phase 2	[8]
E-5324	DM562BM	Hyperlipidaemia	5C80	Discontinued in Phase 2	[9]
Eflucimibe	DMZXRF2	Hyperlipidaemia	5C80	Discontinued in Phase 2	[3]
RP-64477	DMTQ3BS	Hyperlipidaemia	5C80	Discontinued in Phase 2	[10]
447C88	DMC7M3K	Hyperlipidaemia	5C80	Discontinued in Phase 1	[11]
CL-277082	DMSB7WV	Arteriosclerosis	BD40	Discontinued in Phase 1	[12]
F-1394	DMPC9K3	Arteriosclerosis	BD40	Discontinued in Phase 1	[13]
YM-17E	DM0FSA9	Hyperlipidaemia	5C80	Discontinued in Phase 1	[14]
YM-750	DMLD2R0	Hyperlipidaemia	5C80	Discontinued in Phase 1	[15]
CEB-925	DMNJXRG	Hypercholesterolaemia	5C80.0	Terminated	[17]
CI-999	DMV1J0P	Arteriosclerosis	BD40	Terminated	[18]
DuP-129	DMJGCYO	Hypercholesterolaemia	5C80.0	Terminated	[5]
FR-129169	DM9V6AU	Arteriosclerosis	BD40	Terminated	[19]
FR-145237	DMHV43M	Arteriosclerosis	BD40	Terminated	[20]
Lecimibide	DMFEMTG	Hyperlipidaemia	5C80	Terminated	[21]
NTE-122	DMU3D1K	Arteriosclerosis	BD40	Terminated	[22]
RP-70676	DMHO5AG	Hyperlipidaemia	5C80	Terminated	[23]
RP-73163	DMO3FYI	Arteriosclerosis	BD40	Terminated	[24]
TEI-6522	DMHS5DX	Arteriosclerosis	BD40	Terminated	[25]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
HL-004	DMRE52S	Arteriosclerosis	BD40	Preclinical	[16]

113 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(1r)-1,2,2-trimethylpropyl (r)-methylphosphinate	DMVE34H	Discovery agent	N.A.	Investigative	[26]
(E)-Octadec-9-enoic acid phenylamide	DMP7TK0	Discovery agent	N.A.	Investigative	[27]
1,1,1-trifluoro-3-(hexylsulfinyl)propan-2-one	DMJ0ZMT	Discovery agent	N.A.	Investigative	[28]
1,1,1-trifluoro-3-(hexylsulfonyl)propan-2-one	DMWDUCH	Discovery agent	N.A.	Investigative	[28]
1,1,1-trifluoro-3-(hexylthio)propan-2-one	DMWGSP6	Discovery agent	N.A.	Investigative	[28]
1,1,1-trifluoro-3-(octylsulfinyl)propan-2-one	DMLBT0E	Discovery agent	N.A.	Investigative	[28]
1,1,1-trifluoro-3-(octylsulfonyl)propan-2-one	DMT29SN	Discovery agent	N.A.	Investigative	[28]
1,1,1-trifluoro-3-(octylthio)propan-2-one	DMU4EJW	Discovery agent	N.A.	Investigative	[28]
1,1,1-trifluorododecan-2-one	DMW6CQV	Discovery agent	N.A.	Investigative	[28]
1,10-phenanthroline-5,6-dione	DM5LVD2	Discovery agent	N.A.	Investigative	[29]
1,2-bis(2,3,4-trifluorophenyl)-2-hydroxyethanone	DMZSL7H	Discovery agent	N.A.	Investigative	[30]
1,2-bis(2,3,4-trifluorophenyl)ethane-1,2-dione	DML5ECR	Discovery agent	N.A.	Investigative	[30]
1,2-bis(2,3,5-trifluorophenyl)-2-hydroxyethanone	DMD9HP8	Discovery agent	N.A.	Investigative	[30]
1,2-bis(2,3,5-trifluorophenyl)ethane-1,2-dione	DMZHWAV	Discovery agent	N.A.	Investigative	[30]
1,2-bis(2,3,6-trifluorophenyl)ethane-1,2-dione	DMWS2HL	Discovery agent	N.A.	Investigative	[30]
1,2-bis(2,3-difluorophenyl)-2-hydroxyethanone	DMZ0D5W	Discovery agent	N.A.	Investigative	[30]
1,2-bis(2,3-fluorophenyl)ethane-1,2-dione	DM9Z1NY	Discovery agent	N.A.	Investigative	[30]
1,2-bis(2,4-difluorophenyl)-2-hydroxyethanone	DMLMCBW	Discovery agent	N.A.	Investigative	[30]
1,2-bis(2,4-difluorophenyl)ethane-1,2-dione	DMUZHPS	Discovery agent	N.A.	Investigative	[30]
1,2-bis(2,5-difluorophenyl)-2-hydroxyethanone	DM9EW2F	Discovery agent	N.A.	Investigative	[30]
1,2-bis(2,5-difluorophenyl)ethane-1,2-dione	DMVLMBQ	Discovery agent	N.A.	Investigative	[30]
1,2-bis(2,6-difluorophenyl)-2-hydroxyethanone	DMSMVCH	Discovery agent	N.A.	Investigative	[30]
1,2-bis(2,6-difluorophenyl)ethane-1,2-dione	DM351EA	Discovery agent	N.A.	Investigative	[30]
1,2-bis(2-fluorophenyl)-2-hydroxyethanone	DMNWM5S	Discovery agent	N.A.	Investigative	[30]
1,2-bis(2-fluorophenyl)ethane-1,2-dione	DM9FMUE	Discovery agent	N.A.	Investigative	[30]
1,2-bis(3,4,5-trifluorophenyl)-2-hydroxyethanone	DM0LWAV	Discovery agent	N.A.	Investigative	[30]
1,2-bis(3,4,5-trifluorophenyl)ethane-1,2-dione	DMPJT3V	Discovery agent	N.A.	Investigative	[30]
1,2-bis(3,4-difluorophenyl)-2-hydroxyethanone	DMRCUKJ	Discovery agent	N.A.	Investigative	[30]
1,2-bis(3,4-difluorophenyl)ethane-1,2-dione	DMBZ5RN	Discovery agent	N.A.	Investigative	[30]
1,2-bis(3,5-difluorophenyl)-2-hydroxyethanone	DMQTPX2	Discovery agent	N.A.	Investigative	[30]
1,2-bis(3,5-difluorophenyl)ethane-1,2-dione	DM3K5RI	Discovery agent	N.A.	Investigative	[30]
1,2-bis(3-fluorophenyl)-2-hydroxyethanon	DM8XGD0	Discovery agent	N.A.	Investigative	[30]
1,2-bis(3-fluorophenyl)ethane-1,2-dione	DMM3I1P	Discovery agent	N.A.	Investigative	[30]
1,2-bis(4-fluorophenyl)ethane-1,2-dione	DM38Q7W	Discovery agent	N.A.	Investigative	[30]
1,2-Bis-(2-chloro-phenyl)-ethane-1,2-dione	DMZF4IC	Discovery agent	N.A.	Investigative	[31]
1,2-Bis-(3-methoxy-phenyl)-ethane-1,2-dione	DMWY1QN	Discovery agent	N.A.	Investigative	[31]
1,2-Bis-(3-nitro-phenyl)-ethane-1,2-dione	DMGSTKZ	Discovery agent	N.A.	Investigative	[31]
1,2-Bis-(4-bromo-phenyl)-ethane-1,2-dione	DMUW2EJ	Discovery agent	N.A.	Investigative	[31]
1,2-Bis-(4-chloro-phenyl)-ethane-1,2-dione	DM0E5FH	Discovery agent	N.A.	Investigative	[31]
1,2-Bis-(4-methoxy-phenyl)-ethane-1,2-dione	DMCGRV7	Discovery agent	N.A.	Investigative	[31]
1,2-Di-naphthalen-2-yl-ethane-1,2-dione	DMGXMF0	Discovery agent	N.A.	Investigative	[32]
1,2-Di-p-tolyl-ethane-1,2-dione	DMFXB21	Discovery agent	N.A.	Investigative	[31]
1,2-dicyclohexylethane-1,2-dione	DM75OR8	Discovery agent	N.A.	Investigative	[29]
1,2-indanedione	DMV275G	Discovery agent	N.A.	Investigative	[29]
1,2-NAPHTHOQUINONE	DMYXELH	Discovery agent	N.A.	Investigative	[29]
1-(2-bromoethyl)-1H-indole-2,3-dione	DMYF8ES	Discovery agent	N.A.	Investigative	[33]
1-(2-iodoethyl)-1H-indole-2,3-dione	DM1MSAC	Discovery agent	N.A.	Investigative	[33]
1-(3,4-dichlorobenzyl)-1H-indole-2,3-dione	DMX71K9	Discovery agent	N.A.	Investigative	[33]
1-(3,4-Dimethyl-phenyl)-2-phenyl-ethane-1,2-dione	DMCHILK	Discovery agent	N.A.	Investigative	[31]
1-(4-Chloro-phenyl)-2-p-tolyl-ethane-1,2-dione	DMOGVZ2	Discovery agent	N.A.	Investigative	[31]
1-(4-Chloro-phenyl)-2-phenyl-ethane-1,2-dione	DMCDV1O	Discovery agent	N.A.	Investigative	[31]
1-(4-chlorobenzyl)-1H-indole-2,3-dione	DMOUPNT	Discovery agent	N.A.	Investigative	[33]
1-(4-Methoxy-phenyl)-2-phenyl-ethane-1,2-dione	DM5R8KU	Discovery agent	N.A.	Investigative	[31]
1-(4-Nitro-phenyl)-2-phenyl-ethane-1,2-dione	DMOC67J	Discovery agent	N.A.	Investigative	[31]
1-benzyl-1H-indole-2,3-dione	DM2UFXE	Discovery agent	N.A.	Investigative	[33]
1-butyryl-1H-indole-2,3-dione	DMVFCLO	Discovery agent	N.A.	Investigative	[33]
1-dodecyl-1H-indole-2,3-dione	DMK6BWV	Discovery agent	N.A.	Investigative	[33]
1-hexadecyl-1H-indole-2,3-dione	DM4OWM6	Discovery agent	N.A.	Investigative	[33]
1-methyl-1H-indole-2,3-dione	DMPW75L	Discovery agent	N.A.	Investigative	[33]
1-phenyl-1H-indole-2,3-dione	DM74RMP	Discovery agent	N.A.	Investigative	[33]
1-Phenyl-2-p-tolyl-ethane-1,2-dione	DMW9CRT	Discovery agent	N.A.	Investigative	[31]
1-Phenyl-propane-1,2-dione	DM04SWY	Discovery agent	N.A.	Investigative	[31]
1-propionyl-1H-indole-2,3-dione	DM1TNWG	Discovery agent	N.A.	Investigative	[33]
11,12-dihydro-dibenzo[a,e]cyclooctene-5,6-dione	DME0OGM	Discovery agent	N.A.	Investigative	[29]
2,2-Dimethoxy-1,2-diphenyl-ethanone	DM34IX5	Discovery agent	N.A.	Investigative	[31]
2,2-dimethyl-3-methyleneheptadecane	DM7BL04	Discovery agent	N.A.	Investigative	[28]
2-methoxy-3,4-methylenedioxybenzophenone	DM93DYT	Discovery agent	N.A.	Investigative	[34]
3,4,5,6-Tetrachloro-[1,2]benzoquinone	DMSV6K5	Discovery agent	N.A.	Investigative	[31]
3,5-Di-tert-butyl-[1,2]benzoquinone	DMWOB7Q	Discovery agent	N.A.	Investigative	[31]
3-(butylsulfinyl)-1,1,1-trifluoropropan-2-one	DM8PM0E	Discovery agent	N.A.	Investigative	[28]
3-(butylthio)-1,1,1-trifluoropropan-2-one	DM8T2OX	Discovery agent	N.A.	Investigative	[28]
3-(decylsulfinyl)-1,1,1-trifluoropropan-2-one	DMWJ6UD	Discovery agent	N.A.	Investigative	[28]
3-(decylsulfonyl)-1,1,1-trifluoropropan-2-one	DMF27YT	Discovery agent	N.A.	Investigative	[28]
3-(decylthio)-1,1,1-trifluoropropan-2-one	DM1Y6L8	Discovery agent	N.A.	Investigative	[28]
3-(dodecylsulfinyl)-1,1,1-trifluoropropan-2-one	DM7AG6Y	Discovery agent	N.A.	Investigative	[28]
3-(dodecylsulfonyl)-1,1,1-trifluoropropan-2-one	DMPRCS0	Discovery agent	N.A.	Investigative	[28]
4,5-dichloro-1H-indole-2,3-dione	DMX94EK	Discovery agent	N.A.	Investigative	[33]
4,6-dichloro-1H-indole-2,3-dione	DMHBO17	Discovery agent	N.A.	Investigative	[33]
4,7-dichloro-1H-indole-2,3-dione	DMEVK5F	Discovery agent	N.A.	Investigative	[33]
4-(2-Oxo-2-phenyl-acetyl)-benzoic acid	DMFPNQ9	Discovery agent	N.A.	Investigative	[31]
4-chloro-1H-indole-2,3-dione	DM9HXPR	Discovery agent	N.A.	Investigative	[33]
4-chloro-7-methyl-1H-indole-2,3-dione	DM16P3N	Discovery agent	N.A.	Investigative	[33]
4-Piperidino-Piperidine	DMONGDX	Discovery agent	N.A.	Investigative	[26]
5,6-dinitroacenaphthoquinone	DM07HYA	Discovery agent	N.A.	Investigative	[29]
5,7-dichloro-1H-indole-2,3-dione	DMFHDWG	Discovery agent	N.A.	Investigative	[33]
5-(trifluoromethoxy)-1H-indole-2,3-dione	DMK3TEV	Discovery agent	N.A.	Investigative	[33]
5-chloro-1H-indole-2,3-dione	DMQ350F	Discovery agent	N.A.	Investigative	[33]
6,7-dichloro-1H-indole-2,3-dione	DMZHDFM	Discovery agent	N.A.	Investigative	[33]
6-bromo-5-methyl-1H-indole-2,3-dione	DMFZ2PI	Discovery agent	N.A.	Investigative	[33]
7-(trifluoromethyl)-1H-indole-2,3-dione	DM46VT2	Discovery agent	N.A.	Investigative	[33]
7-chloro-1H-indole-2,3-dione	DMCZLKA	Discovery agent	N.A.	Investigative	[33]
Acenanthrene-9,10-dione	DMU9O7K	Discovery agent	N.A.	Investigative	[29]
ACENAPHTHOQUINONE	DMU3DMH	Discovery agent	N.A.	Investigative	[29]
Alpha-D-Mannose	DMF5DLW	Discovery agent	N.A.	Investigative	[1]
BENZIL	DM5Y2M8	Discovery agent	N.A.	Investigative	[28]
Benzoin	DM50QMB	Discovery agent	N.A.	Investigative	[30]
CHLORANIL	DMCHGF1	Discovery agent	N.A.	Investigative	[31]
Dibutyl 2,2,2-trifluoro-1-phenylethyl phosphate	DM2G8ON	Discovery agent	N.A.	Investigative	[35]
Diethyl 2,2,2-trifluoro-1-phenylethyl phosphate	DMDJ9QA	Discovery agent	N.A.	Investigative	[35]
Dimethyl 2,2,2-trifluoro-1-phenylethyl phosphate	DMTVA49	Discovery agent	N.A.	Investigative	[35]
Heptane-2,3-dione	DMCFTB8	Discovery agent	N.A.	Investigative	[31]
KY-382	DMA9VBD	Arteriosclerosis	BD40	Investigative	[5]
N-Methylnaloxonium	DMXSJH0	Discovery agent	N.A.	Investigative	[36]
NSC-23180	DMJ91Y7	Discovery agent	N.A.	Investigative	[29]
O-Sialic Acid	DMCAR7B	Discovery agent	N.A.	Investigative	[26]
Oleic acid anilide	DMXCSVH	Discovery agent	N.A.	Investigative	[34]
Phenanthrene-9,10-dione	DMG8KS9	Discovery agent	N.A.	Investigative	[29]
PYRIPYROPENE A	DMCTJAM	Discovery agent	N.A.	Investigative	[27]
SCH-48375	DM0J937	Discovery agent	N.A.	Investigative	[37]
SMP-797	DMSI95J	Discovery agent	N.A.	Investigative	[38]
Thenoyltrifluoroacetone	DM54OKX	Discovery agent	N.A.	Investigative	[39]
Thieno[3,2-e][1]benzothiophene-4,5-dione	DMT74N6	Discovery agent	N.A.	Investigative	[29]
VULM-1457	DMWRX4T	Arteriosclerosis	BD40	Investigative	[5]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Coronary artery disease	BA80-BA8Z	Peripheral blood	1.13E-01	-0.03	-0.06
Familial hypercholesterolemia	5A11	Whole blood	3.82E-08	1.86	1.9

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Carboxylesterase 1 (CES1) DME Info
• Gene Name: CES1

9 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Candesartan	DMRK8OT	Chronic heart failure	BD1Z	Approved	[40]
Dexmethylphenidate	DMUQE2A	Attention deficit hyperactivity disorder	6A05.Z	Approved	[41]
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[42]
Fenofibrate	DMFKXDY	Coronary atherosclerosis		Approved	[]
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[43]
Methylphenidate	DM7SJD6	Attention deficit hyperactivity disorder	6A05.Z	Approved	[44]
PSI-7977	DMLSUWZ	HCV 1-6 infection	1E51	Approved	[45]
Rufinamide	DMWE60C	Epilepsy	8A60-8A68	Approved	[46]
Salbutamol	DMN9CWF	Acute asthma	CA23	Approved	[47]

5 Clinical Trial Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dabigatran etexilate	DMRDZ4X	Venous thromboembolism	BD72	Phase 3	[48]
MK-4827	DMLYGH4	Ovarian cancer	2C73	Phase 3	[49]
Pradaxa	DM2ZYX9	Stroke	8B20	Phase 3	[50]
TA-6366	DMR32KN	N. A.	N. A.	Phase 3	[51]
E6005	DM1S489	Atopic dermatitis	EA80	Phase 2	[52]

1 Investigative Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nitrophenyl acetate	DMHSD8A	N. A.	N. A.	Investigative	[53]

References

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