Molecule Information

General Information of the Molecule (ID: Mol00357)

• Name: Liver carboxylesterase 1 (CES1) ,Homo sapiens
• Synonyms: Acyl-coenzyme A:cholesterol acyltransferase; ACAT; Brain carboxylesterase hBr1; Carboxylesterase 1; CE-1; hCE-1; Cholesteryl ester hydrolase; CEH; Cocaine carboxylesterase; Egasyn; HMSE; Methylumbelliferyl-acetate deacetylase 1; Monocyte/macrophage serine esterase; Retinyl ester hydrolase; REH; Serine esterase 1; Triacylglycerol hydrolase; TGH; CES2; SES1
• Molecule Type: Protein
• Gene Name: CES1
• Gene ID: 1066
• Location: chr16:55802851-55833337[-]
• 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.
• Uniprot ID: EST1_HUMAN
• Ensembl ID: ENSG00000198848
• HGNC ID: HGNC:1863

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Clopidogrel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Hypo-attenuated leaflet thickening [1]

• Resistant Disease: Hypo-attenuated leaflet thickening [ICD-11: BD10.2]
• Resistant Drug: Clopidogrel
• Molecule Alteration: SNP; rs8192950
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: We thoroughly genotyped 34 SNPs and 8 SNPs that have been reported for clopidogrel and aspirin resistance. A total of 148 patients were enrolled. There were 15 patients demonstrating signs of HALT. Patients with HALT had a higher rate of atrial fibrillation (AF) pre-TAVR (33.3 vs. 7.5%, P = 0.01).

Temocapril hydrochloride

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Haemorrhage [2]

• Resistant Disease: Haemorrhage [ICD-11: MG27.0]
• Resistant Drug: Temocapril hydrochloride
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: CaCo2 cells; Colon; Homo sapiens (Human); CVCL_0025
• In Vitro Model: IPS cells; Colon; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: Transcellular transport study assay
• Mechanism Description: The extraction ratio value of metabolism of temocapril (a CES1 substrate) to temocaprilat in the absence and presence of 500 uM BNPP (a CES inhibitor) in hiPSC-IECs were 4.17 +/- 0.22 (%) and 5.18 +/- 0.30 (%), respectively. In contrast, the extraction ratio in Caco-2 cells was 99.0 +/- 0.1 (%) and decreased to 1.29 +/- 0.07 (%) in the presence of 500 uM BNPP.

References

• Ref 1: Gene polymorphisms in dual antiplatelet therapy and the presence of hypo-attenuated leaflet thickening after transcatheter aortic valve replacement .J Thromb Thrombolysis. 2018 Apr;45(3):463-465. doi: 10.1007/s11239-018-1636-z. 10.1007/s11239-018-1636-z
• Ref 2: Application of Intestinal Epithelial Cells Differentiated from Human Induced Pluripotent Stem Cells for Studies of Prodrug Hydrolysis and Drug Absorption in the Small Intestine. Drug Metab Dispos. 2018 Nov;46(11):1497-1506. doi: 10.1124/dmd.118.083246. Epub 2018 Aug 22.