Molecule Information

General Information of the Molecule (ID: Mol00358)

• Name: Cocaine esterase (CES2) ,Homo sapiens
• Synonyms: Carboxylesterase 2; CE-2; hCE-2; Methylumbelliferyl-acetate deacetylase 2; ICE
• Molecule Type: Protein
• Gene Name: CES2
• Gene ID: 8824
• Location: chr16:66934444-66945096[+]
• 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.
• Uniprot ID: EST2_HUMAN
• Ensembl ID: ENSG00000172831
• HGNC ID: HGNC:1864

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) 1 drug(s) in total

Irinotecan

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Colorectal cancer [1]

• Resistant Disease: Colorectal cancer [ICD-11: 2B91.1]
• Resistant Drug: Irinotecan
• 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 of metabolism of irinotecan (a CES2 substrate) to SN-38 in hiPSC-IECs was 3.52 +/- 0.15 (%) and decreased to 2.42 +/- 0.17 (%) in the presence of 100 uM telmisartan (a CES2 inhibitor). The extraction ratio in Caco-2 cells was 3.96 +/- 0.55 (%) and also decreased to 2.30 +/- 0.30 (%) in the presence of 100 uM telmisartan.

References

• Ref 1: 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.