CES1

Summary

CES1 (carboxylesterase 1, HGNC:1863) is a protein-coding gene on chromosome 16q12.2, encoding Liver carboxylesterase 1 (P23141). Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs.

This gene encodes a member of the carboxylesterase large family. The family members are responsible for the hydrolysis or transesterification of various xenobiotics, such as cocaine and heroin, and endogenous substrates with ester, thioester, or amide bonds. They may participate in fatty acyl and cholesterol ester metabolism, and may play a role in the blood-brain barrier system. This enzyme is the major liver enzyme and functions in liver drug clearance. Mutations of this gene cause carboxylesterase 1 deficiency. Three transcript variants encoding three different isoforms have been found for this gene.

Source: NCBI Gene 1066 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 126 total — 2 pathogenic
• Phenotypes (HPO): 2
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001025195

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1863
Approved symbol	CES1
Name	carboxylesterase 1
Location	16q12.2
Locus type	gene with protein product
Status	Approved
Aliases	HMSE, CES2, HMSE1, SES1, CEH, CES1A1, CES1A2
Ensembl gene	ENSG00000198848
Ensembl biotype	protein_coding
OMIM	114835
Entrez	1066

Gene structure

Transcript identifiers

Ensembl transcripts: 61 — 56 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000360526, ENST00000361503, ENST00000422046, ENST00000563005, ENST00000563241, ENST00000565403, ENST00000565568, ENST00000566555, ENST00000569260, ENST00000905467, ENST00000905468, ENST00000905469, ENST00000905470, ENST00000905471, ENST00000905472, ENST00000905473, ENST00000905474, ENST00000905475, ENST00000905476, ENST00000905477, ENST00000905478, ENST00000905479, ENST00000905480, ENST00000905481, ENST00000905482, ENST00000905483, ENST00000905484, ENST00000905485, ENST00000905486, ENST00000905487, ENST00000905488, ENST00000905489, ENST00000905490, ENST00000905491, ENST00000905492, ENST00000905493, ENST00000905494, ENST00000905495, ENST00000905496, ENST00000905497, ENST00000905498, ENST00000905499, ENST00000905500, ENST00000905501, ENST00000905502, ENST00000905503, ENST00000905504, ENST00000905505, ENST00000905506, ENST00000905507, ENST00000905508, ENST00000905509, ENST00000932715, ENST00000969253, ENST00000969254, ENST00000969255, ENST00000969256, ENST00000969257, ENST00000969258, ENST00000969259, ENST00000969260

RefSeq mRNA: 3 — MANE Select: NM_001025195 NM_001025194, NM_001025195, NM_001266

CCDS: CCDS32450, CCDS45488, CCDS45489

Canonical transcript exons

ENST00000360526 — 14 exons

Exon	Start	End
ENSE00001406175	55810517	55810664
ENSE00001411104	55833004	55833096
ENSE00001616061	55819535	55819639
ENSE00001643285	55816924	55816962
ENSE00001662852	55828767	55828974
ENSE00001740876	55812903	55813043
ENSE00001745793	55820372	55820479
ENSE00002577016	55802851	55803232
ENSE00003463713	55826151	55826295
ENSE00003519414	55806333	55806464
ENSE00003573347	55821368	55821521
ENSE00003576041	55823550	55823683
ENSE00003644140	55810927	55811010
ENSE00003664969	55803529	55803601

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 99.81.

FANTOM5 (CAGE): breadth broad, TPM avg 17.2911 / max 2428.3188, expressed in 467 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157456	16.7074	461
157455	0.5134	100
157457	0.0703	39

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.81	gold quality
liver	UBERON:0002107	99.77	gold quality
gall bladder	UBERON:0002110	99.46	gold quality
right lung	UBERON:0002167	99.27	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.23	gold quality
upper lobe of left lung	UBERON:0008952	98.40	gold quality
lower esophagus mucosa	UBERON:0035834	98.26	gold quality
lung	UBERON:0002048	97.80	gold quality
smooth muscle tissue	UBERON:0001135	97.57	gold quality
apex of heart	UBERON:0002098	97.14	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.74	gold quality
descending thoracic aorta	UBERON:0002345	96.51	gold quality
colonic epithelium	UBERON:0000397	96.45	gold quality
right atrium auricular region	UBERON:0006631	96.16	gold quality
prostate gland	UBERON:0002367	95.75	gold quality
popliteal artery	UBERON:0002250	95.65	gold quality
tibial artery	UBERON:0007610	95.64	gold quality
spleen	UBERON:0002106	95.53	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.28	gold quality
thoracic aorta	UBERON:0001515	95.26	gold quality
left uterine tube	UBERON:0001303	95.16	gold quality
ascending aorta	UBERON:0001496	95.14	gold quality
urinary bladder	UBERON:0001255	95.09	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.09	gold quality
fallopian tube	UBERON:0003889	94.64	gold quality
myometrium	UBERON:0001296	94.38	gold quality
lower esophagus	UBERON:0013473	94.38	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.36	gold quality
adipose tissue	UBERON:0001013	94.34	gold quality
left coronary artery	UBERON:0001626	94.34	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-126	yes	1400.80
E-GEOD-130473	yes	463.82
E-HCAD-9	yes	56.53
E-CURD-112	yes	14.83
E-HCAD-11	yes	10.13
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, NR1I2, SP1, TFCP2, VSX2

miRNA regulators (miRDB)

7 targeting CES1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-6772-3P	97.04	65.89	784
HSA-MIR-4448	97.04	66.22	752

Literature-anchored findings (GeneRIF, showing 40)

• crystal structure bound to analogs of cocaine and heroin (PMID:12679808)
• A serine esterase involved in both drug metabolism and activation. (PMID:12773168)
• Altered expression is associated with therapy failure and death in patients with multiple types of cancer. (PMID:15931389)
• Findings indicate that F417 but not L418, L420, or C390 participates in substrate hydrolysis by triacylglycerol hydrolase. (PMID:16282638)
• Using multisite promiscuity, carboxylesterase 1 appears structurally capable of assembling several catalytic events, depending upon the physiological state of the cellular environment. (PMID:16962139)
• Cholesteryl ester hydrolase expression in human macrophages is potential target for attenuation of foam cell formation and regression of atherosclerotic plaques. (PMID:16971496)
• IL-6 alters the cellular responsiveness to clopidogrel, irinotecan, and oseltamivir by suppressing the expression of CES1. (PMID:17537833)
• comparative analysis of CES1 and CES2 in liver and small intestine of humans, monkeys, dogs, rabbits and rats (PMID:17764701)
• Carboxylesterase 1A1 mRNA expression level is much higher than the expression of carboxylesterase 1A2 mRNA in the liver and lung. (PMID:18305377)
• SNP haplotype in the CES1A2 promoter affects the Sp1 binding and transcriptional regulation; it well agreed with the efficacy of the medication of imidapril. (PMID:18328811)
• In vitro functional studies demonstrated the catalytic functions of both p.Gly143Glu and p.Asp260fs are substantially impaired, resulting in a complete loss of hydrolytic activity toward methylphenidate. (PMID:18485328)
• hepatic CEH regulates the last step of RCT by promoting the flux of cholesterol entering the liver via SR-BI and increasing hepatic bile acid output [cholesteryl ester hydrolase] (PMID:18599737)
• pharmacogenomic characterization of human carboxylesterase 1A1, 1A2, and 1A3 genes (PMID:18794728)
• Carboxylesterases play critical roles in drug metabolism and insecticide detoxication; findings show large variability among different age groups or even within the same age group. (PMID:18983829)
• CES1 mutations Gly143Glu and Asp260fs are essentially dysfunctional enzymes with regard to the conversion of trandolapril to its more active metabolite trandolaprilat. (PMID:19185566)
• CES1 expression was linked to body fat and adipocyte fat content but not to lipolytic activity. (PMID:19332024)
• A comparison of the substrate specificity of CES1 versus CES2 reveals broad but distinct substrate preferences. (PMID:19508181)
• The high-resolution proteomic approach demonstrates that hCE1 is a good candidate for further validation as a serologic glycoprotein biomarker for HCC. (PMID:19658107)
• Luciferase assays revealed that the antioxidant response element (ARE) at -2025 in the CES1A1 gene was responsible for the transactivation by Nrf2 (PMID:19715681)
• We observed an association with the rare 143Glu-variant: 5 patients in the responder group carrying the Glu-allele required lower doses of MPH for symptom reduction. (PMID:19733552)
• Molecular dynamics results emphasize properties of the CES1 catalytic cavity, confirming that CES1 prefers substrates with relatively smaller and somewhat polar alkyl/aryl groups and larger hydrophobic acyl moieties. (PMID:19932971)
• The knockdown of CES1 with siRNA resulted in lower levels of HCV replication, and up-regulation of CES1 was observed to favor HCV propagation, implying an important role for this host cell protein. (PMID:20530478)
• Report CES1 mediated hydrolysis of heroin, cocaine and CPT-11. (PMID:20649590)
• Dysregulation of genes such as CES1 and APOE seems to be associated with some physiopathological markers of insulin resistance and cardiovascular risk factors in obesity. (PMID:20975297)
• High mRNA levels of CES1 is associated with adiposity and lipolysis, thereby contributing to the development of obesity-associated phenotypes. (PMID:21081832)
• The comparison of the genotyping results between this novel assay and those previously reported methods highlighted the necessity of applying the discriminative genotyping assay in pharmacogenetic studies involving CES1 gene. (PMID:22237548)
• tested the hypothesis that an individual’s CES phenotype can be characterized by reporter substrates/probes that interrogate native CES1 and CES2 activities in liver and immunoblotting methods (PMID:22525521)
• Genetic variability in Carboxylesterase 1 affects the pharmacokinetics of oseltamivir and indicate that CES1 plays an important role in the bioactivation of oseltamivir in humans. (PMID:22588607)
• An influence of carboxylesterase 1 -75 T>G polymorphism on the worsening of appetite reduction with MPH treatment in youths with ADHD. (PMID:22688218)
• This study provides the first evidence of functional compensation whereby increased expression of CES3 restores intracellular cholesteryl ester hydrolytic activity and free cholesterol efflux in CES1-deficient cells. (PMID:22700792)
• The CES1 SNP rs8192950 AC genotype and rs1968753 GG genotype might be the candidates for risk prediction of antituberculosis drug-induced hepatotoxicity. (PMID:22943824)
• Genetic variation in CES1 may be an important determinant of the efficacy of clopidogrel. (PMID:23111421)
• Deficient CES1 catalytic activity resulting from CES1 inhibition. (PMID:23275066)
• Carboxylesterase 1 gene duplication and mRNA expression in adipose tissue are linked to obesity and metabolic function. (PMID:23468884)
• carboxylesterase I controls RhoA methylation (PMID:23658012)
• PMPMEase overexpression in colorectal cancer and cancer cell death stemming from its inhibition is an indication of its possible role in cancer progression and a target for chemopreventive agents (PMID:23936796)
• CES1 plays a role in the metabolism of several drugs. (PMID:24141856)
• The conversion of 2-oxo-ticlopidine to M1 was further confirmed with recombinant paraoxonase 1 (PON1) and CES1. (PMID:24170778)
• After oral administration of dabigatran etexilate to humans, DABE is hydrolyzed by intestinal CES2 to the intermediate M2 metabolite followed by hydrolysis of M2 to DAB in the liver by CES1. (PMID:24212379)
• study found an association between two CES1 SNP markers and the occurrence of sadness as a side effect of short-acting methylphenidate (PMID:24350812)

Cross-species orthologs

62 orthologs

Organism	Symbol	Gene ID
danio_rerio	ces2a	ENSDARG00000041569
danio_rerio	ces3	ENSDARG00000041595
danio_rerio	si:ch73-89b15.3	ENSDARG00000053709
danio_rerio	si:dkey-30c15.17	ENSDARG00000058492
danio_rerio	nlgn3b	ENSDARG00000062376
danio_rerio	nlgn2b	ENSDARG00000079251
danio_rerio	si:ch211-71n6.4	ENSDARG00000102234
mus_musculus	Ces1d	ENSMUSG00000056973
mus_musculus	Ces1g	ENSMUSG00000057074
mus_musculus	Ces1c	ENSMUSG00000057400
mus_musculus	Ces1h	ENSMUSG00000074156
mus_musculus	Ces1b	ENSMUSG00000078964
rattus_norvegicus	Ces1e	ENSRNOG00000015438
rattus_norvegicus	Ces1dl1	ENSRNOG00000015519
rattus_norvegicus		ENSRNOG00000079343
rattus_norvegicus	Ces1f	ENSRNOG00000091108
drosophila_melanogaster	Est-6	FBGN0000592
drosophila_melanogaster	Est-P	FBGN0000594
drosophila_melanogaster	Glt	FBGN0001114
drosophila_melanogaster	Gli	FBGN0001987
drosophila_melanogaster	Jhe	FBGN0010052
drosophila_melanogaster	alpha-Est1	FBGN0015568
drosophila_melanogaster	alpha-Est10	FBGN0015569
drosophila_melanogaster	alpha-Est2	FBGN0015570
drosophila_melanogaster	alpha-Est3	FBGN0015571
drosophila_melanogaster	alpha-Est4	FBGN0015572
drosophila_melanogaster	alpha-Est6	FBGN0015574
drosophila_melanogaster	alpha-Est7	FBGN0015575
drosophila_melanogaster	alpha-Est8	FBGN0015576
drosophila_melanogaster	alpha-Est9	FBGN0015577
drosophila_melanogaster	CG4757	FBGN0027584
drosophila_melanogaster	CG9287	FBGN0032057
drosophila_melanogaster	CG9289	FBGN0032058
drosophila_melanogaster	CG3841	FBGN0032131
drosophila_melanogaster	CG4382	FBGN0032132
drosophila_melanogaster	Jhedup	FBGN0034076
drosophila_melanogaster	gas	FBGN0034736
drosophila_melanogaster	Nlg3	FBGN0083963
drosophila_melanogaster	alpha-Est5	FBGN0261393
caenorhabditis_elegans		WBGENE00000037
caenorhabditis_elegans		WBGENE00000038
caenorhabditis_elegans		WBGENE00001578
caenorhabditis_elegans		WBGENE00006412
caenorhabditis_elegans		WBGENE00007691
caenorhabditis_elegans		WBGENE00007692
caenorhabditis_elegans		WBGENE00007693
caenorhabditis_elegans		WBGENE00007695
caenorhabditis_elegans		WBGENE00008451
caenorhabditis_elegans		WBGENE00011362
caenorhabditis_elegans		WBGENE00011364
caenorhabditis_elegans		WBGENE00013873
caenorhabditis_elegans		WBGENE00013874
caenorhabditis_elegans		WBGENE00013875
caenorhabditis_elegans		WBGENE00015067
caenorhabditis_elegans		WBGENE00015071
caenorhabditis_elegans		WBGENE00015279
caenorhabditis_elegans		WBGENE00015284
caenorhabditis_elegans		WBGENE00016595
caenorhabditis_elegans		WBGENE00016862
caenorhabditis_elegans		WBGENE00016863
caenorhabditis_elegans	cest-27	WBGENE00018958
caenorhabditis_elegans		WBGENE00020688

Paralogs (13): TG (ENSG00000042832), ACHE (ENSG00000087085), BCHE (ENSG00000114200), NLGN4X (ENSG00000146938), CES5A (ENSG00000159398), NLGN4Y (ENSG00000165246), NLGN1 (ENSG00000169760), NLGN2 (ENSG00000169992), CEL (ENSG00000170835), CES4A (ENSG00000172824), CES3 (ENSG00000172828), CES2 (ENSG00000172831), NLGN3 (ENSG00000196338)

Protein

Protein identifiers

Liver carboxylesterase 1 — P23141 (reviewed: P23141)

Alternative names: Acyl-coenzyme A:cholesterol acyltransferase, Brain carboxylesterase hBr1, Carboxylesterase 1, Cholesteryl ester hydrolase, Cocaine carboxylesterase, Egasyn, HMSE, Methylumbelliferyl-acetate deacetylase 1, Monocyte/macrophage serine esterase, Retinyl ester hydrolase, Serine esterase 1, Triacylglycerol hydrolase

All UniProt accessions (4): P23141, H3BQR4, H3BQV8, H3BSU0

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Homotrimer and homohexamer. Binds to beta-glucuronidase.

Subcellular location. Endoplasmic reticulum lumen. Cytoplasm. Lipid droplet.

Tissue specificity. Expressed predominantly in liver with lower levels in heart and lung. Expressed in macrophages.

Post-translational modifications. Contains sialic acid. Cleavage of the signal sequence can occur at 2 positions, either between Trp-17 and Gly-18 or between Gly-18 and His-19.

Activity regulation. Activated by CHAPS. Inhibited by chlorpyrifos oxon (IC(50)=0.21 nM), paraoxon (IC(50)=0.29 nM), or methyl paraoxon (IC(50)=49 nM).

Polymorphism. Genetic variants in CES1 are associated with clinically significant alterations in pharmacokinetics and drug response of carboxylesterase 1 substrates [MIM:618057].

Miscellaneous. Involved in the activation pathway of bemnifosbuvir (AT-527) and its epimer, AT-752. AT-527 and AT-752 are two guanosine analogs tested in clinical trials against several RNA viruses, which are activated into their common 5’-triphosphate AT-9010 in human cells. Mediates the first activation step by catalyzing transformation of AT-527 and AT-75 into AT-551.

Similarity. Belongs to the type-B carboxylesterase/lipase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P23141-1	1	yes
P23141-2	2
P23141-3	3

RefSeq proteins (3): NP_001020365, NP_001020366, NP_001257 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002018	CarbesteraseB	Domain
IPR019819	Carboxylesterase_B_CS	Conserved_site
IPR019826	Carboxylesterase_B_AS	Active_site
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR050309	Type-B_Carboxylest/Lipase	Family

Pfam: PF00135

Enzyme classification (BRENDA):

• EC 3.1.1.1 — carboxylesterase (BRENDA: 126 organisms, 1207 substrates, 1167 inhibitors, 834 Km, 540 kcat entries)

Substrate kinetics (BRENDA)

286 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
4-NITROPHENYL ACETATE	0.013–4.47	61
4-NITROPHENYL HEXANOATE	0.004–44.7	41
4-NITROPHENYL BUTYRATE	0.0004–1.6	39
4-NITROPHENYL BUTANOATE	0.004–127	32
4-NITROPHENYL OCTANOATE	0.0117–25.2	31
4-NITROPHENYL DODECANOATE	0.0008–67.6	26
4-NITROPHENYL PROPIONATE	0.0338–3.3	18
4-NITROPHENYL PENTANOATE	0.02–2.1	14
4-NITROPHENYL DECANOATE	0.008–4.99	13
4-NITROPHENYL HEXADECANOATE	0.005–4.8	12
4-YETHYLUMBELLIFERYL ACETATE	0.022–2	9
7-ETHYL-10-[4-(1-PIPERIDINO)-1-AMINO]CARBONYLOXY	0.0555–0.0851	9
CPT-11	58.05–81.01	9
1-NAPHTHYL ACETATE	0.008–1.01	8
4-NITROPHENYL CAPROATE	0.008–3.8	8

Catalyzed reactions (Rhea), 7 shown:

• 4-methylumbelliferyl acetate + H2O = 4-methylumbelliferone + acetate + H(+) (RHEA:12208)
• a carboxylic ester + H2O = an alcohol + a carboxylate + H(+) (RHEA:21164)
• 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = glycerol + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) (RHEA:26132)
• cholesteryl (9Z-octadecenoate) + H2O = cholesterol + (9Z)-octadecenoate + H(+) (RHEA:33875)
• a cholesterol ester + H2O = cholesterol + a fatty acid + H(+) (RHEA:36403)
• prostaglandin E2 1-glyceryl ester + H2O = prostaglandin E2 + glycerol + H(+) (RHEA:48296)
• prostaglandin F2alpha 1-glyceryl ester + H2O = prostaglandin F2alpha + glycerol + H(+) (RHEA:48300)

UniProt features (110 total): sequence conflict 32, helix 28, strand 22, turn 7, sequence variant 5, mutagenesis site 5, active site 3, splice variant 2, disulfide bond 2, signal peptide 1, chain 1, modified residue 1, glycosylation site 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
5A7G	X-RAY DIFFRACTION	1.48
9KWL	X-RAY DIFFRACTION	1.83
5A7F	X-RAY DIFFRACTION	1.86
9KWM	X-RAY DIFFRACTION	1.89
2H7C	X-RAY DIFFRACTION	2
5A7H	X-RAY DIFFRACTION	2.01
4AB1	X-RAY DIFFRACTION	2.2
1MX1	X-RAY DIFFRACTION	2.4
8EOR	ELECTRON MICROSCOPY	2.67
2HRQ	X-RAY DIFFRACTION	2.7
2HRR	X-RAY DIFFRACTION	2.7
1MX5	X-RAY DIFFRACTION	2.8
2DQZ	X-RAY DIFFRACTION	2.8
1MX9	X-RAY DIFFRACTION	2.9
1YA8	X-RAY DIFFRACTION	3
1YAH	X-RAY DIFFRACTION	3
2DQY	X-RAY DIFFRACTION	3
3K9B	X-RAY DIFFRACTION	3.1
1YA4	X-RAY DIFFRACTION	3.2
1YAJ	X-RAY DIFFRACTION	3.2
2DR0	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23141-F1	93.27	0.87

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 221 (acyl-ester intermediate); 354 (charge relay system); 468 (charge relay system)

Post-translational modifications (1): 380

Disulfide bonds (2): 87–116, 274–285

Glycosylation sites (1): 79

Mutagenesis-validated functional residues (5):

Position	Phenotype
79	abolishes glycosylation.
221	loss of activity.
354	loss of activity.
468	loss of activity.
564–567	does not result in secretion.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2022377	Metabolism of Angiotensinogen to Angiotensins
R-HSA-211945	Phase I - Functionalization of compounds
R-HSA-5578768	Physiological factors
R-HSA-9749641	Aspirin ADME

MSigDB gene sets: 456 (showing top): GOBP_CELLULAR_RESPONSE_TO_LIPOPROTEIN_PARTICLE_STIMULUS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_FATTY_ACID_CATABOLIC_PROCESS, GOBP_REGULATION_OF_LIPID_STORAGE, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_ACID_SECRETION, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, chr16q22, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, GOBP_STEROL_HOMEOSTASIS, GOBP_CELLULAR_RESPONSE_TO_LIPID, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, GNF2_GSTM1, MODULE_151

GO Biological Process (17): cholesterol biosynthetic process (GO:0006695), cholesterol metabolic process (GO:0008203), response to toxic substance (GO:0009636), positive regulation of cholesterol efflux (GO:0010875), negative regulation of cholesterol storage (GO:0010887), lipid catabolic process (GO:0016042), epithelial cell differentiation (GO:0030855), cholesterol homeostasis (GO:0042632), reverse cholesterol transport (GO:0043691), medium-chain fatty acid metabolic process (GO:0051791), regulation of bile acid biosynthetic process (GO:0070857), cellular response to cholesterol (GO:0071397), cellular response to low-density lipoprotein particle stimulus (GO:0071404), cholesterol ester hydrolysis involved in cholesterol transport (GO:0090122), positive regulation of cholesterol metabolic process (GO:0090205), regulation of bile acid secretion (GO:0120188), lipid metabolic process (GO:0006629)

GO Molecular Function (6): sterol ester esterase activity (GO:0004771), methylumbelliferyl-acetate deacetylase activity (GO:0047374), carboxylic ester hydrolase activity (GO:0052689), carboxylesterase activity (GO:0106435), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (5): cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), lipid droplet (GO:0005811), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Peptide hormone metabolism	1
Biological oxidations	1
Cardiac conduction	1
Drug ADME	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cholesterol metabolic process	3
carboxylic ester hydrolase activity	3
cellular anatomical structure	2
cytoplasm	2
sterol biosynthetic process	1
secondary alcohol biosynthetic process	1
sterol metabolic process	1
secondary alcohol metabolic process	1
response to chemical	1
regulation of cholesterol efflux	1
positive regulation of cholesterol transport	1
cholesterol efflux	1
cholesterol storage	1
regulation of cholesterol storage	1
negative regulation of lipid storage	1
lipid metabolic process	1
catabolic process	1
cell differentiation	1
epithelium development	1
sterol homeostasis	1
cholesterol transport	1
fatty acid metabolic process	1
bile acid biosynthetic process	1
regulation of ketone metabolic process	1
regulation of steroid biosynthetic process	1
regulation of small molecule metabolic process	1
cellular response to sterol	1
response to cholesterol	1
cellular response to alcohol	1
response to lipoprotein particle	1
cellular response to lipoprotein particle stimulus	1
vesicle-mediated cholesterol transport	1
positive regulation of steroid metabolic process	1
positive regulation of small molecule metabolic process	1
regulation of cholesterol metabolic process	1
bile acid secretion	1
regulation of organic acid transport	1
regulation of secretion	1
primary metabolic process	1
lipase activity	1

Protein interactions and networks

STRING

1410 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CES1	NCEH1	Q6PIU2	884
CES1	MGLL	Q99685	807
CES1	RNGTT	O60942	798
CES1	ESD	P10768	791
CES1	LIPE	Q05469	777
CES1	CLEC14A	Q86T13	776
CES1	GUSB	P08236	756
CES1	CTSA	P10619	717
CES1	HINT1	P49773	714
CES1	AADAC	P22760	679
CES1	TNFRSF13C	Q96RJ3	615
CES1	CYP3A4	P05184	592
CES1	A6NFB4	A6NFB4	583
CES1	PNPLA2	Q96AD5	571
CES1	SOAT1	P35610	570

IntAct

9 interactions, top by confidence:

A	B	Type	Score
CES1	PB2	psi-mi:“MI:0915”(physical association)	0.370
PB1	CES1	psi-mi:“MI:0915”(physical association)	0.370
CREB3	CES1	psi-mi:“MI:0915”(physical association)	0.370
SRRT	A2ML1	psi-mi:“MI:0914”(association)	0.350
PRXL2A	A2ML1	psi-mi:“MI:0914”(association)	0.350
GPC3	PXDNL	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (33): CES1 (Two-hybrid), CES1 (Co-crystal Structure), CES1 (Two-hybrid), CES1 (Two-hybrid), CES1 (Two-hybrid), CES1 (Two-hybrid), CES1 (Two-hybrid), CES1 (Two-hybrid), KPRP (Two-hybrid), CES1 (Proximity Label-MS), CES1 (Proximity Label-MS), CES1 (Proximity Label-MS), CES1 (Proximity Label-MS), CES1 (Proximity Label-MS), CES1 (Proximity Label-MS)

ESM2 similar proteins: A0A8B0RBM2, G3V7J5, O00748, O42275, O46421, O70631, P04058, P07140, P07692, P07882, P0C6R3, P10959, P12337, P14943, P16303, P23141, P23953, P30122, P32749, P56161, Q03311, Q04791, Q27677, Q29550, Q5GRG2, Q5RCL7, Q5XG92, Q63010, Q63108, Q63880, Q64176, Q64285, Q64419, Q64573, Q6AW46, Q6AW47, Q6NT32, Q6UWW8, Q8BK48, Q8I034

Diamond homologs: A0A060S684, A0A0E4AET8, A0A8B0RBM2, B0F2B4, D2D3B6, D6WMZ8, G3V7J5, I1RDA9, O00748, O16168, O16169, O16170, O16171, O16172, O16173, O42275, O46421, O62760, O62761, O70631, P04058, P06276, P07882, P08171, P0C6R3, P10959, P12337, P12992, P14943, P16303, P16854, P18142, P19835, P21837, P21927, P23141, P23953, P25725, P25726, P25727

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

126 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	97
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
17602	NM_001025195.2(CES1):c.428G>A (p.Gly143Glu)	Pathogenic
17603	NM_001025195.2(CES1):c.783del (p.Asp261fs)	Pathogenic

SpliceAI

3924 predictions. Top by Δscore:

Variant	Effect	Δscore
16:55803598:CCCT:C	acceptor_gain	1.0000
16:55803599:CCTC:C	acceptor_gain	1.0000
16:55810512:CTCA:C	donor_loss	1.0000
16:55810513:TCAC:T	donor_loss	1.0000
16:55810514:CACCT:C	donor_loss	1.0000
16:55810515:A:AG	donor_loss	1.0000
16:55810516:CCT:C	donor_gain	1.0000
16:55810926:CAA:C	donor_gain	1.0000
16:55810944:T:TA	donor_gain	1.0000
16:55810945:C:A	donor_gain	1.0000
16:55819530:CCTA:C	donor_loss	1.0000
16:55819531:CTACC:C	donor_loss	1.0000
16:55819532:TAC:T	donor_loss	1.0000
16:55819533:A:AC	donor_gain	1.0000
16:55819533:AC:A	donor_gain	1.0000
16:55819533:ACCAT:A	donor_loss	1.0000
16:55819534:C:A	donor_loss	1.0000
16:55819534:C:CC	donor_gain	1.0000
16:55819534:CC:C	donor_gain	1.0000
16:55819534:CCA:C	donor_gain	1.0000
16:55819534:CCAT:C	donor_gain	1.0000
16:55819635:ATTTG:A	acceptor_gain	1.0000
16:55819636:TTTG:T	acceptor_gain	1.0000
16:55819637:TTG:T	acceptor_gain	1.0000
16:55819638:TG:T	acceptor_gain	1.0000
16:55820367:CCTA:C	donor_loss	1.0000
16:55820369:TAC:T	donor_loss	1.0000
16:55820370:A:C	donor_loss	1.0000
16:55820371:C:CA	donor_loss	1.0000
16:55820477:AACC:A	acceptor_loss	1.0000

AlphaMissense

3704 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:55821397:A:G	S221P	0.996
16:55821494:G:C	N188K	0.991
16:55821494:G:T	N188K	0.991
16:55823575:G:T	R171S	0.991
16:55826205:A:C	C116W	0.990
16:55803540:A:C	F503L	0.989
16:55803540:A:T	F503L	0.989
16:55803542:A:G	F503L	0.989
16:55821380:A:C	S226R	0.989
16:55821380:A:T	S226R	0.989
16:55821382:T:G	S226R	0.989
16:55821481:C:G	D193H	0.989
16:55826197:A:G	L119P	0.989
16:55826292:G:C	C87W	0.989
16:55828859:A:C	F55L	0.989
16:55828859:A:T	F55L	0.989
16:55828861:A:G	F55L	0.989
16:55821434:A:C	F208L	0.988
16:55821434:A:T	F208L	0.988
16:55821436:A:G	F208L	0.988
16:55821460:A:G	W200R	0.988
16:55821460:A:T	W200R	0.988
16:55821468:G:T	A197D	0.988
16:55823575:G:C	R171G	0.988
16:55820429:A:C	S247R	0.986
16:55820429:A:T	S247R	0.986
16:55820431:T:G	S247R	0.986
16:55821480:T:A	D193V	0.986
16:55823574:C:G	R171P	0.986
16:55828874:G:C	F50L	0.986

dbSNP variants (sampled 300 via entrez): RS1000024830 (16:55831153 G>A), RS1004618326 (16:55819564 C>A,G,T), RS1009852928 (16:55819991 A>C,G), RS1018412781 (16:55816743 G>A,C), RS1023291080 (16:55811524 C>A), RS1056737475 (16:55830811 A>C,G,T), RS11076114 (16:55831876 C>A,G), RS11076116 (16:55834858 A>C,G,T), RS111238132 (16:55827556 A>G), RS111303103 (16:55818372 T>C), RS111357269 (16:55831267 G>A), RS111387345 (16:55816840 G>A,C), RS111399497 (16:55820683 C>A,T), RS111414219 (16:55820279 C>A), RS111494334 (16:55811172 T>TG,TGG)

Disease associations

OMIM: gene MIM:114835 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0020169	Abnormal drug response

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001895_1	Response to dabigatran etexilate treatment	5.000000e-07
GCST001895_2	Response to dabigatran etexilate treatment	1.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2265 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 45,775 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL15192	LAPACHONE	2	589
CHEMBL169	URSOLIC ACID	2	20,825
CHEMBL230006	ENOXOLONE	2	24,361

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

16 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs200707504	Metabolism/PK	3	oseltamivir
rs2244613	Toxicity	3	dabigatran	Atrial Fibrillation
rs2244613	Toxicity	3	capecitabine	Drug Toxicity
rs2244614	Toxicity	3	capecitabine	Drug Toxicity
rs2307240	Efficacy	3	clopidogrel	Acute coronary syndrome
rs3217164	Toxicity	3	capecitabine	Drug Toxicity
rs71647871	Efficacy	2B	clopidogrel
rs71647871	Metabolism/PK	2B	clopidogrel
rs71647871	Metabolism/PK	3	methylphenidate
rs71647871	Dosage	3	methylphenidate	Attention Deficit Disorder with Hyperactivity
rs71647871	Metabolism/PK	3	enalapril
rs71647871	Metabolism/PK	3	heroin
rs71647871	Metabolism/PK	3	sacubitril
rs778068631	Metabolism/PK	3	clopidogrel
rs8192935	Metabolism/PK	3	dabigatran	Atrial Fibrillation
rs8192950	Efficacy	3	clopidogrel	Cerebrovascular Disorders;Stroke;Transient Ischemic Attack

PharmGKB variants

29 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2002577	CES1		0.00	0
rs2244613	CES1	3	4.75	2	dabigatran;capecitabine
rs2307240	CES1	3	3.50	1	clopidogrel
rs3815583	CES1		0.00	0
rs12443580	CES1		0.00	0
rs71647871	CES1	2B	6.75	7	methylphenidate;sacubitril;clopidogrel;enalapril;heroin
rs121912777	CES1		0.00	0
rs8192935	CES1	3	1.25	1	dabigatran
rs8192950	CES1	3	2.25	1	clopidogrel
rs3217164	CES1	3	3.00	1	capecitabine
rs2244614	CES1	3	3.00	1	capecitabine
rs200707504	CES1	3	0.12	1	oseltamivir
rs1968753	CES1		0.00	0
rs151291296	CES1		0.00	0
rs146456965	CES1		0.00	0
rs201065375	CES1		0.00	0
rs143718310	CES1		0.00	0
rs202121317	CES1		0.00	0
rs2307243	CES1		0.00	0
rs202001817	CES1		0.00	0
rs9921399	CES1		0.00	0
rs778068631	CES1	3	0.00	1	clopidogrel
rs147055479	CES1		0.00	0
rs115629050	CES1		0.00	0
rs4513095	CES1		0.00	0
rs114119971	CES1		0.00	0
rs4122238	CES1		0.00	0
rs74019272	CES1		0.00	0
rs2307227	CES1		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Hydrolases & Lipases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
GR148672X	Inhibition	8.4	pIC50

Binding affinities (BindingDB)

15 measured of 166 human assays (167 total across all organisms); most potent 15 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(R)-(2-phenylpiperidin-1-yl)(3-(4-(pyridin-3-yl)phenyl)-1H-1,2,4-triazol-1-yl)methanone (5)	IC50	5 nM
(R)-(3-(4-(2-morpholinopyrimidin-5-yl)phenyl)-1H-1,2,4-triazol-1-yl)(2-phenylpiperidin-1-yl)methanone (6)	IC50	5 nM
(R)-4’-(1-(2-phenylpiperidine-1-carbonyl)-1H-1,2,4-triazol-3-yl)-[1,1’-biphenyl]-4-sulfonamide (4)	IC50	7 nM
6-chloro-2-methoxyacridin-9-amine	KI	49 nM
2,3,5,6-tetrachlorocyclohexa-2,5-diene-1,4-dione	KI	163 nM
7-ethoxyacridine-3,9-diamine	KI	490 nM
2-nitro-9,10-dihydrophenanthrene-9,10-dione	KI	850 nM
5,6-dinitro-1,2-dihydroacenaphthylenedione	KI	903 nM
1,4-Benzoquinone	KI	955 nM
3,4,5,6-tetrachlorocyclohexa-3,5-diene-1,2-dione	KI	1670 nM
1-{[4-({4-[(2,3-dioxo-2,3-dihydro-1H-indol-1-yl)methyl]phenyl}methyl)phenyl]methyl}-2,3-dihydro-1H-indole-2,3-dione	KI	3280 nM
3,5-di-tert-butylcyclohexa-3,5-diene-1,2-dione	IC50	9840 nM
1,2-Dione-Based Compound, 8	IC50	18400 nM
cid_1901244	KI	48200 nM
5,6-dihydro-1=10-phenantroline-5,6-dione	IC50	123000 nM

ChEMBL bioactivities

430 potent at pChembl≥5 of 484 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.54	Ki	0.029	nM	CHEMBL193228
9.52	Ki	0.302	nM	CHEMBL467451
9.48	Ki	0.328	nM	CHEMBL4290236
9.40	Ki	0.3981	nM	CHEMBL467450
9.40	Ki	0.3981	nM	CHEMBL463556
9.38	Ki	0.417	nM	CHEMBL4293626
9.30	IC50	0.5	nM	CHEMBL413727
9.30	Ki	0.5012	nM	CHEMBL464002
9.22	Ki	0.6026	nM	CHEMBL460807
9.22	Ki	0.6026	nM	CHEMBL460806
9.15	Ki	0.7079	nM	CHEMBL449775
9.15	IC50	0.7	nM	CHEMBL448922
9.08	Ki	0.84	nM	CHEMBL1812859
9.00	IC50	1	nM	CHEMBL91416
9.00	IC50	1	nM	CHEMBL175854
9.00	Ki	1	nM	CHEMBL449475
8.82	Ki	1.5	nM	CHEMBL235503
8.80	Ki	1.6	nM	CHEMBL192139
8.70	IC50	2	nM	CHEMBL93675
8.68	Ki	2.1	nM	CHEMBL362996
8.66	Ki	2.2	nM	CHEMBL190672
8.66	Ki	2.19	nM	CHEMBL1812864
8.64	Ki	2.291	nM	CHEMBL86668
8.62	Ki	2.4	nM	CHEMBL4282357
8.60	Ki	2.5	nM	9,10-PHENANTHRENEQUINONE
8.54	IC50	2.92	nM	CHEMBL4849361
8.52	IC50	3	nM	CHEMBL367966
8.52	Ki	3	nM	CHEMBL1812856
8.48	Ki	3.311	nM	CHEMBL460808
8.44	Ki	3.6	nM	CHEMBL4285759
8.40	IC50	4	nM	CHEMBL293277
8.40	Ki	3.981	nM	CHEMBL270374
8.38	Ki	4.169	nM	CHEMBL89506
8.37	IC50	4.29	nM	CHEMBL4855755
8.35	Ki	4.44	nM	CHEMBL4101254
8.35	IC50	4.5	nM	CHEMBL261172
8.33	Ki	4.7	nM	CHEMBL4071772
8.32	Ki	4.8	nM	CHEMBL1812857
8.31	Ki	4.9	nM	CHEMBL4090451
8.30	IC50	5	nM	CHEMBL91417
8.30	IC50	5	nM	CHEMBL179760
8.30	IC50	5	nM	CHEMBL182199
8.30	Ki	5	nM	CHEMBL235287
8.29	IC50	5.17	nM	CHEMBL4853637
8.28	Ki	5.248	nM	CHEMBL440542
8.27	Ki	5.4	nM	CHEMBL192180
8.27	IC50	5.4	nM	CHEMBL273139
8.27	Ki	5.37	nM	CHEMBL402615
8.26	IC50	5.5	nM	CHEMBL270373
8.22	Ki	6.026	nM	CHEMBL510996

PubChem BioAssay actives

509 with measured affinity, of 1193 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1,2-bis(4-bromophenyl)ethane-1,2-dione	239005: Inhibition constant against human liver carboxylesterase 1 using 4-MUA (4-methylumbelliferone acetate)	ki	<0.0001	uM
3-decylsulfonyl-1,1,1-trifluoropropane-2,2-diol	412234: Inhibition of human carboxylesterase 1 after 24 hrs	ki	0.0003	uM
5,15,15-trimethyl-3,8-dioxatetracyclo[8.8.0.02,6.011,16]octadeca-1(10),2(6),4,11(16),17-pentaene-7,9-dione	1423181: Inhibition of human CE1 using o-NPA as substrate	ki	0.0003	uM
(5R)-5,15,15-trimethyl-3,8-dioxatetracyclo[8.8.0.02,6.011,16]octadeca-1(10),2(6),11(16),17-tetraene-7,9-dione	1423181: Inhibition of human CE1 using o-NPA as substrate	ki	0.0004	uM
3-dodecylsulfinyl-1,1,1-trifluoropropane-2,2-diol	412234: Inhibition of human carboxylesterase 1 after 24 hrs	ki	0.0004	uM
3-dodecylsulfonyl-1,1,1-trifluoropropane-2,2-diol	412234: Inhibition of human carboxylesterase 1 after 24 hrs	ki	0.0004	uM
3-decylsulfinyl-1,1,1-trifluoropropane-2,2-diol	412234: Inhibition of human carboxylesterase 1 after 24 hrs	ki	0.0005	uM
1,1,1-trifluoro-7-phenylheptan-2-one	241415: Inhibitory concentration against Triacylglycerol hydrolase	ic50	0.0005	uM
1,1,1-trifluoro-3-octylsulfinylpropane-2,2-diol	412234: Inhibition of human carboxylesterase 1 after 24 hrs	ki	0.0006	uM
1,1,1-trifluoro-3-octylsulfonylpropane-2,2-diol	412234: Inhibition of human carboxylesterase 1 after 24 hrs	ki	0.0006	uM
1-(1,2,4-oxadiazol-5-yl)-7-phenylheptan-1-one	365839: Inhibition of TGH	ic50	0.0007	uM
1,1,1-trifluoro-3-hexylsulfonylpropane-2,2-diol	412234: Inhibition of human carboxylesterase 1 after 24 hrs	ki	0.0007	uM
octadecane-9,10-dione	612130: Inhibition of human liver carboxylesterase1 using o-nitrophenyl acetate as substrate after 5 mins by spectrophotometry	ki	0.0008	uM
1-([1,3]oxazolo[4,5-b]pyridin-2-yl)-6-phenylhexan-1-one	241415: Inhibitory concentration against Triacylglycerol hydrolase	ic50	0.0010	uM
1,1,1-trifluoro-3-hexoxypropane-2,2-diol	412234: Inhibition of human carboxylesterase 1 after 24 hrs	ki	0.0010	uM
1,1,1-trifluoro-8-phenyloctan-2-one	241415: Inhibitory concentration against Triacylglycerol hydrolase	ic50	0.0010	uM
aceanthrylene-1,2-dione	1798260: Enzyme Inhibition Assay from Article 10.1021/jm0706867: “Planarity and constraint of the carbonyl groups in 1,2-diones are determinants for selective inhibition of human carboxylesterase 1.”	ki	0.0015	uM
1,2-bis(4-chlorophenyl)ethane-1,2-dione	239005: Inhibition constant against human liver carboxylesterase 1 using 4-MUA (4-methylumbelliferone acetate)	ki	0.0016	uM
1,1,1-trifluorononan-2-one	241415: Inhibitory concentration against Triacylglycerol hydrolase	ic50	0.0020	uM
1-[4-(2-oxo-2-phenylacetyl)phenyl]-2-phenylethane-1,2-dione	239005: Inhibition constant against human liver carboxylesterase 1 using 4-MUA (4-methylumbelliferone acetate)	ki	0.0021	uM
1,2-bis(4-bromothiophen-2-yl)ethane-1,2-dione	239708: Inhibition constant against human liver carboxylesterase (hCE1) expressed in Sf21 cells using 3 mM o-NPA	ki	0.0022	uM
1-phenyloctane-1,2-dione	612130: Inhibition of human liver carboxylesterase1 using o-nitrophenyl acetate as substrate after 5 mins by spectrophotometry	ki	0.0022	uM
1,1,1-trifluorododecan-2-one	412234: Inhibition of human carboxylesterase 1 after 24 hrs	ki	0.0023	uM
5,15-dimethyl-3,8-dioxatetracyclo[8.8.0.02,6.011,16]octadeca-1(10),2(6),4,11,13,15,17-heptaene-7,9-dione	1423181: Inhibition of human CE1 using o-NPA as substrate	ki	0.0024	uM
phenanthrene-9,10-dione	1798260: Enzyme Inhibition Assay from Article 10.1021/jm0706867: “Planarity and constraint of the carbonyl groups in 1,2-diones are determinants for selective inhibition of human carboxylesterase 1.”	ki	0.0025	uM
ethyl (Z)-4,4,4-trifluoro-3-hydroxy-2-[(4-methylphenyl)diazenyl]but-2-enoate	1762416: Inhibition of human recombinant CES1 expressed in baculovirus infected BTI insect cells using 4-NPA as substrate by spectrophotometric analysis	ic50	0.0029	uM
1-([1,3]oxazolo[4,5-b]pyridin-2-yl)-7-phenylheptan-1-one	241415: Inhibitory concentration against Triacylglycerol hydrolase	ic50	0.0030	uM
dodecane-6,7-dione	612130: Inhibition of human liver carboxylesterase1 using o-nitrophenyl acetate as substrate after 5 mins by spectrophotometry	ki	0.0030	uM
1,1,1-trifluoro-3-hexylsulfinylpropane-2,2-diol	412234: Inhibition of human carboxylesterase 1 after 24 hrs	ki	0.0033	uM
(5R)-5,15-dimethyl-3,8-dioxatetracyclo[8.8.0.02,6.011,16]octadeca-1(10),2(6),11,13,15,17-hexaene-7,9-dione	1423181: Inhibition of human CE1 using o-NPA as substrate	ki	0.0036	uM
3-decylsulfanyl-1,1,1-trifluoropropan-2-one	412234: Inhibition of human carboxylesterase 1 after 24 hrs	ki	0.0040	uM
2,2,2-trifluoro-1-phenylethanone	241415: Inhibitory concentration against Triacylglycerol hydrolase	ic50	0.0040	uM
1,1,1-trifluoro-3-octylsulfanylpropan-2-one	412234: Inhibition of human carboxylesterase 1 after 24 hrs	ki	0.0042	uM
ethyl (Z)-4,4,4-trifluoro-3-hydroxy-2-[(4-methoxyphenyl)diazenyl]but-2-enoate	1762416: Inhibition of human recombinant CES1 expressed in baculovirus infected BTI insect cells using 4-NPA as substrate by spectrophotometric analysis	ic50	0.0043	uM
4-(4-methylphenoxy)naphthalene-1,2-dione	1431882: Inhibition of human liver CES1 expressed in baculovirus infected sf9 cells using o-nitrophenyl acetate as substrate monitored at 15 secs interval for 5 mins	ki	0.0044	uM
1-(1,3-oxazol-2-yl)-3-(4-phenylphenyl)propan-1-one	316865: Inhibition of TGH	ic50	0.0045	uM
4-(4-iodophenoxy)naphthalene-1,2-dione	1431882: Inhibition of human liver CES1 expressed in baculovirus infected sf9 cells using o-nitrophenyl acetate as substrate monitored at 15 secs interval for 5 mins	ki	0.0047	uM
tetradecane-7,8-dione	612130: Inhibition of human liver carboxylesterase1 using o-nitrophenyl acetate as substrate after 5 mins by spectrophotometry	ki	0.0048	uM
4-(N,4-dimethylanilino)naphthalene-1,2-dione	1431891: Inhibition of human liver CES1 expressed in baculovirus infected sf9 cells using oseltamivir as substrate	ki	0.0049	uM
1,2-dicyclohexylethane-1,2-dione	612130: Inhibition of human liver carboxylesterase1 using o-nitrophenyl acetate as substrate after 5 mins by spectrophotometry	ki	0.0050	uM
4-[4-[2-[(2S)-2-phenylpiperidine-1-carbonyl]triazol-4-yl]phenyl]benzoic acid	1801982: Gel-based ABPP (CES1) from Article 10.1021/acschembio.6b00266: “Discovery of a Selective Covalent Inhibitor of Lysophospholipase-like 1 (LYPLAL1) as a Tool to Evaluate the Role of this Serine Hydrolase in Metabolism.”	ic50	0.0050	uM
4-[4-[2-[(2R)-2-phenylpiperidine-1-carbonyl]triazol-4-yl]phenyl]benzoic acid	1801982: Gel-based ABPP (CES1) from Article 10.1021/acschembio.6b00266: “Discovery of a Selective Covalent Inhibitor of Lysophospholipase-like 1 (LYPLAL1) as a Tool to Evaluate the Role of this Serine Hydrolase in Metabolism.”	ic50	0.0050	uM
N,N-dimethyl-4-[4-[2-[(2R)-2-phenylpiperidine-1-carbonyl]triazol-4-yl]phenyl]benzenesulfonamide	1801982: Gel-based ABPP (CES1) from Article 10.1021/acschembio.6b00266: “Discovery of a Selective Covalent Inhibitor of Lysophospholipase-like 1 (LYPLAL1) as a Tool to Evaluate the Role of this Serine Hydrolase in Metabolism.”	ic50	0.0050	uM
[(2R)-2-phenylpiperidin-1-yl]-[3-(4-pyridin-3-ylphenyl)-1,2,4-triazol-1-yl]methanone	1801982: Gel-based ABPP (CES1) from Article 10.1021/acschembio.6b00266: “Discovery of a Selective Covalent Inhibitor of Lysophospholipase-like 1 (LYPLAL1) as a Tool to Evaluate the Role of this Serine Hydrolase in Metabolism.”	ic50	0.0050	uM
[3-[4-(2-morpholin-4-ylpyrimidin-5-yl)phenyl]-1,2,4-triazol-1-yl]-[(2R)-2-phenylpiperidin-1-yl]methanone	1801982: Gel-based ABPP (CES1) from Article 10.1021/acschembio.6b00266: “Discovery of a Selective Covalent Inhibitor of Lysophospholipase-like 1 (LYPLAL1) as a Tool to Evaluate the Role of this Serine Hydrolase in Metabolism.”	ic50	0.0050	uM
1-([1,3]oxazolo[4,5-b]pyridin-2-yl)-8-phenyloctan-1-one	241808: Inhibitory concentration of triacylgylcerol hydrolase using FP-Rh radioligand	ic50	0.0050	uM
1-([1,3]oxazolo[4,5-b]pyridin-2-yl)-9-phenylnonan-1-one	241808: Inhibitory concentration of triacylgylcerol hydrolase using FP-Rh radioligand	ic50	0.0050	uM
1,1,1-trifluoro-9-phenylnonan-2-one	241415: Inhibitory concentration against Triacylglycerol hydrolase	ic50	0.0050	uM
1,1,1-trifluoro-3-hexylsulfanylpropan-2-one	412234: Inhibition of human carboxylesterase 1 after 24 hrs	ki	0.0052	uM
ethyl (Z)-4,4,4-trifluoro-3-hydroxy-2-[(3-methylphenyl)diazenyl]but-2-enoate	1762416: Inhibition of human recombinant CES1 expressed in baculovirus infected BTI insect cells using 4-NPA as substrate by spectrophotometric analysis	ic50	0.0052	uM

CTD chemical–gene interactions

187 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cocaine	decreases reaction, increases chemical synthesis, increases hydrolysis, affects cotreatment, increases metabolic processing (+1 more)	5
4-nitrophenyl acetate	increases hydrolysis, decreases metabolic processing, affects binding, increases chemical synthesis, increases metabolic processing (+1 more)	4
Heroin	decreases reaction, affects binding, decreases acetylation, increases hydrolysis	4
Methylphenidate	decreases reaction, increases hydrolysis, decreases metabolic processing, increases abundance, increases chemical synthesis (+1 more)	4
bioresmethrin	decreases reaction, increases metabolic processing, increases hydrolysis	3
Irinotecan	increases hydrolysis, increases response to substance	3
Acetaminophen	increases expression, decreases expression	3
Cholesterol	increases metabolic processing, increases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression	3
Arachidonic Acid	decreases reaction, affects cotreatment, decreases activity, increases chemical synthesis, increases hydrolysis	3
Permethrin	affects hydrolysis, increases hydrolysis	3
Oseltamivir	affects hydrolysis, decreases activity, decreases metabolic processing, decreases reaction, increases abundance (+1 more)	3
mitragynine	increases hydrolysis, decreases activity, decreases metabolic processing	2
bisphenol A	affects expression, increases expression	2
sulforaphane	increases activity, affects reaction, increases expression, affects binding, increases reaction	2
decamethrin	affects hydrolysis, decreases reaction, increases activity, increases metabolic processing	2
4-nitrophenol	affects metabolic processing, increases chemical synthesis, increases hydrolysis	2
6-O-monoacetylmorphine	affects binding, increases chemical synthesis, decreases reaction	2
4-nitrophenyl butyrate	affects binding, increases hydrolysis	2
temocapril hydrochloride	increases hydrolysis	2
imidapril	increases activity, increases hydrolysis, increases metabolic processing, decreases reaction	2
cocaethylene	increases chemical synthesis	2
homatropine	increases metabolic processing, affects binding	2
Ethanol	affects cotreatment, increases metabolic processing	2
Dexamethasone	increases expression	2
Naloxone	affects binding, increases metabolic processing	2
Paraoxon	decreases activity	2
Phenobarbital	increases expression	2
Trinitrobenzenesulfonic Acid	increases expression	2
Valproic Acid	decreases methylation, increases expression	2

ChEMBL screening assays

110 unique, capped per target: 57 binding, 53 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1019596	Binding	Inhibition of human carboxylesterase 1	Comparison of benzil and trifluoromethyl ketone (TFK)-mediated carboxylesterase inhibition using classical and 3D-quantitative structure-activity relationship analysis. — Bioorg Med Chem
CHEMBL3118932	ADMET	Metabolic stability of the compound assessed as recombinant carboxylesterase-1 (unknown origin)-mediated hydrolysis by chromatographic analysis	Undesired versus designed enzymatic cleavage of linkers for liver targeting. — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1VR	Abcam A-549 CES1 KO	Cancer cell line	Male
CVCL_D2N8	Abcam THP-1 CES1 KO	Cancer cell line	Male
CVCL_E1CS	Ubigene THP-1 CES1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.