According to one definition, xenobiotics are alien compounds that interfere with an organism's natural metabolism. Many xenobiotics can have a number of harmful effects if they don't have metabolism. There are several phase 1 metabolizing enzymes of xenobiotics which have capability to detoxify the toxic compounds. Several important metabolic detoxication enzymes are presented, including the mammalian microsomal cytochrome Carboxylesterases. Mammalian carboxyleterases are key enzymes from the serine hydrolase enzyme. Carboxylesterases (CEs) are usually considered as a xenobiotic metabolizing enzymes that hydrolyze esterified xenobiotics into some products of alcohol and carboxylic acid. These proteins metabolize a large number of therapeutically useful medications, which affects how well medicinal treatments work. Xenobiotics are foreign compounds that can disrupt normal metabolic processes, necessitating their detoxification through enzymatic metabolism. Human carboxylesterases (CEs), a critical class of serine hydrolases, play a key role in the hydrolysis of esterified xenobiotics into alcohol and carboxylic acid derivatives, aiding in their elimination. These enzymes, predominantly expressed in the liver and gastrointestinal tract, contribute significantly to drug metabolism, influencing therapeutic efficacy and detoxification pathways. This review explores the structure, function, and biological significance of CEs, particularly CES1 and CES2, in xenobiotic metabolism. Their role in processing pharmaceutical agents, environmental pollutants, and endogenous substrates underscores their pharmacological importance. Furthermore, interindividual variations in CE activity affect drug bioavailability and toxicity, highlighting the need for further research into CE modulators and inhibitors. Understanding the metabolic role of CEs can enhance drug development strategies and improve therapeutic interventions for xenobiotic exposure.

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1. Joseph P. Transcriptomics in toxicology. Food Chem Toxicol. 2017;109(Pt 1):650–62. doi:10.1016/j.fct.2017.07.031.
2. Mansuy D. Le métabolisme des xénobiotiques: effets bénéfiques, effets néfastes. Biol Aujourd’hui. 2013;207(1):33–7. doi:10.1051/jbio/2013003.
3. Patterson AD, Gonzalez FJ, Idle JR. Xenobiotic metabolism: a view through the metabolometer. Chem Res Toxicol. 2010;23(5):851–60. doi:10.1021/tx100020p.
4. Detoxification and Substance Abuse Treatment. Treatment Improvement Protocol (TIP) Series. Rockville (MD); 2006.
5. Kreitinger JM, Beamer CA, Shepherd DM. Environmental immunology: Lessons learned from exposure to a select panel of immunotoxicants. J Immunol. 2016;196(8):3217–25. doi:10.4049/jimmunol.1502149.
6. Croom E. Metabolism of xenobiotics of human environments. Prog Mol Biol Transl Sci. 2012;112:31–88. doi:10.1016/B978-0-12-415813-9.00003-9.
7. Godin SJ, Scollon EJ, Hughes MF, Potter PM, DeVito MJ, Ross MK. Species differences in the in vitro metabolism of deltamethrin and esfenvalerate: differential oxidative and hydrolytic metabolism by humans and rats. Drug Metab Dispos. 2006;34(10):1764–71. doi:10.1124/dmd.106.010058.
8. Sterri SH, Fonnum F. The Role of Carboxylesterases in Therapeutic Intervention of Nerve Gases Poisoning. In: Handbook of Toxicology of Chemical Warfare Agents. 2015.
9. Yan B. Carboxylesterases. In: Encyclopedia of Toxicology. Elsevier; 2014. p. 695–8.
10. Bachmann K. Drug Metabolism. In: Pharmacology. Elsevier; 2009. p. 131–73.
11. Koppel N, Maini Rekdal V, Balskus EP. Chemical transformation of xenobiotics by the human gut microbiota. Science. 2017;356(6344). doi:10.1126/science.aag2770.
12. Abdelsalam NA, Ramadan AT, ElRakaiby MT, Aziz RK. Toxicomicrobiomics: The human microbiome vs. pharmaceutical, dietary, and environmental xenobiotics. Front Pharmacol. 2020;11:390. doi:10.3389/fphar.2020.00390.
13. Clarke G, Sandhu KV, Griffin BT, Dinan TG, Cryan JF, Hyland NP. Gut reactions: breaking down xenobiotic-microbiome interactions. Pharmacol Rev. 2019;71:198–224. doi:10.1124/pr.118.015768.
14. Wang D, Zou L, Jin Q, Hou J, Ge G, Yang L. Human carboxylesterases: a comprehensive review. Acta Pharm Sin B. 2018;8(5):699–712. doi:10.1016/j.apsb.2018.05.005.
15. Hatfield MJ, Umans RA, Hyatt JL, Edwards CC, Wierdl M, Tsurkan L, et al. Carboxylesterases: General detoxifying enzymes. Chem Biol Interact. 2016;259(Pt B):327–31. doi:10.1016/j.cbi.2016.02.011.
16. Sanghani SP, Sanghani PC, Schiel MA, Bosron WF. Human carboxylesterases: an update on CES1, CES2 and CES3. Protein Pept Lett. 2009;16:1207–14. doi:10.2174/092986609789071324.
17. Satoh T, Hosokawa M. Structure, function and regulation of carboxylesterases. Chem Biol Interact. 2006;162:195–211. doi:10.1016/j.cbi.2006.07.001.
18. Satoh T, Hosokawa M. The mammalian carboxylesterases: from molecules to functions. Annu Rev Pharmacol Toxicol. 1998;38:257–88. doi:10.1146/annurev.pharmtox.38.1.257.
19. Ross MK, Crow JA. Human carboxylesterases and their role in xenobiotic and endobiotic metabolism. J Biochem Mol Toxicol. 2007;21:187–96. doi:10.1002/jbt.20178.
20. Hosokawa M. Structure and catalytic properties of carboxylesterase isozymes involved in metabolic activation of prodrugs. Molecules. 2008;13:412–31. doi:10.3390/molecules13020412.
21. Imai T. Human carboxylesterase isozymes: catalytic properties and rational drug design. Drug Metab Pharmacokinet. 2006;21:173–85. doi:10.2133/dmpk.21.173.
22. Redinbo MR, Potter PM. Mammalian carboxylesterases: from drug targets to protein therapeutics. Drug Discov Today. 2005;10:313–25. doi:10.1016/S1359-6446(05)03383-0.
23. Satoh T, Taylor P, Bosron WF, Sanghani SP, Hosokawa M, La Du BN. Current progress on esterases: from molecular structure to function. Drug Metab Dispos. 2002;30:488–93. doi:10.1124/dmd.30.5.488.
24. Potter PM, Wolverton JS, Morton CL, Wierdl M, Danks MK. Cellular localization domains of a rabbit and a human carboxylesterase: influence on irinotecan (CPT-11) metabolism by the rabbit enzyme. Cancer Res. 1998;58:3627–32.
25. Zhu HJ, Wang X, Gawronski BE, Brinda BJ, Angiolillo DJ, Markowitz JS. Carboxylesterase 1 as a determinant of clopidogrel metabolism and activation. J Pharmacol Exp Ther. 2013;344:665–72. doi:10.1124/jpet.112.201640.
26. Zhu HJ, Markowitz JS. Activation of the antiviral prodrug oseltamivir is impaired by two newly identified carboxylesterase 1 variants. Drug Metab Dispos. 2009;37:264–7. doi:10.1124/dmd.108.024943.
27. Nishi K, Huang H, Kamita SG, Kim IH, Morisseau C, Hammock BD. Characterization of pyrethroid hydrolysis by the human liver carboxylesterases CES-1 and CES-2. Arch Biochem Biophys. 2006;445:115–23. doi:10.1016/j.abb.2005.11.005.
28. Imai T, Ohura K. The role of intestinal carboxylesterase in the oral absorption of prodrugs. Curr Drug Metab. 2010;11:793–805. doi:10.2174/138920010794328904.
29. Lian J, Nelson R, Lehner R. Carboxylesterases in lipid metabolism: from mouse to human. Protein Cell. 2018;9(3):178–95. doi:10.1007/s13238-017-0437-z.
30. Alam M, Ho S, Vance DE, Lehner R. Heterologous expression, purification, and characterization of human triacylglycerol hydrolase. Protein Expr Purif. 2002;24(1):33–42. doi:10.1006/prep.2001.1553.
31. Ruby MA, Massart J, Hunerdosse DM, Schönke M, Correia JC, Louie SM. Human carboxylesterase 2 reverses obesity-induced diacylglycerol accumulation and glucose intolerance. Cell Rep. 2017;18(3):636–46. doi:10.1016/j.celrep.2016.12.070.
32. Crow JA, Herring KL, Xie S, Borazjani A, Potter PM, Ross MK. Inhibition of carboxylesterase activity of THP1 monocytes/macrophages and recombinant human carboxylesterase 1 by oxysterols and fatty acids. Biochim Biophys Acta. 2010;1801(1):31–41. doi:10.1016/j.bbalip.2009.09.002.
33. Alam M, Vance DE, Lehner R. Structure-function analysis of human triacylglycerol hydrolase by site-directed mutagenesis: identification of the catalytic triad and a glycosylation site. Biochemistry. 2002;41(21):6679–87. doi:10.1021/bi0255625.
34. Wang DD, Zou LW, Jin Q, Hou J, Ge GB, Yang L. Recent progress in the discovery of natural inhibitors against human carboxylesterases. Fitoterapia. 2017;117:84–95. doi:10.1016/j.fitote.2017.01.010.
35. Dominguez E, Galmozzi A, Chang JW, Hsu KL, Pawlak J, Li W. Integrated phenotypic and activity-based profiling links Ces3 to obesity and diabetes. Nat Chem Biol. 2014;10(2):113–21. doi:10.1038/nchembio.1429.
36. Crow JA, Middleton BL, Borazjani A, Hatfield MJ, Potter PM, Ross MK. Inhibition of carboxylesterase 1 is associated with cholesteryl ester retention in human THP-1 monocyte/macrophages. Biochim Biophys Acta. 2008;1781(12):643–54. doi:10.1016/j.bbalip.2008.07.005.
37. Yoon KJP, Hyatt JL, Morton CL, Lee RE, Potter PM, Danks MK. Characterization of inhibitors of specific carboxylesterases: development of carboxylesterase inhibitors for translational application. Mol Cancer Ther. 2004;3(7):903–9.
38. Xu Y, Zhang C, He W, Liu D. Regulations of xenobiotics and endobiotics on carboxylesterases: a comprehensive review. Eur J Drug Metab Pharmacokinet. 2016;41(4):321–30. doi:10.1007/s13318-016-0326-5.
39. Hicks LD, Hyatt JL, Stoddard S, Tsurkan L, Edwards CC, Wadkins RM. Improved, selective, human intestinal carboxylesterase inhibitors designed to modulate irinotecan (CPT-11) toxicity. J Med Chem. 2009;52(12):3742–52. doi:10.1021/jm9001296.
40. Aranda J, Cerqueira NMFS, Fernandes PA, Roca M, Tuñon I, Ramos MJ. The catalytic mechanism of carboxylesterases: a computational study. Biochemistry. 2014;53(36):5820–9. doi:10.1021/bi500934j.
41. Liebler DC, Guengerich FP. Elucidating mechanisms of drug-induced toxicity. Nat Rev Drug Discov. 2005;4(5):410–20. doi:10.1038/nrd1720.
42. Chambers JP, Hartgraves SL, Murphy MR, Wayner MJ, Kumar N, Valdes JJ. Effects of three reputed carboxylesterase inhibitors upon rat serum esterase activity. Neurosci Biobehav Rev. 1991;15(1):85–8. doi:10.1016/s0149-7634(05)80096-x.
43. Cashman JR, Perotti BY, Berkman CE, Lin J. Pharmacokinetics and molecular detoxication. Environ Health Perspect. 1996;104 Suppl 1:23–40. doi:10.1289/ehp.96104s123.
44. Jones RD, Taylor AM, Tong EY, Repa JJ. Carboxylesterases are uniquely expressed among tissues and regulated by nuclear hormone receptors in the mouse. Drug Metab Dispos. 2013;41(1):40–9. doi:10.1124/dmd.112.048397.
45. Ross MK, Crow JA. Human carboxylesterases and their role in xenobiotic and endobiotic metabolism. J Biochem Mol Toxicol. 2007;21(4):187–96. doi:10.1002/jbt.20178.
46. Tsujita T, Okuda H. The synthesis of fatty acid ethyl ester by carboxylester lipase. Eur J Biochem. 1994;224(1):57–62. doi:10.1111/j.1432-1033.1994.tb19994.x.
47. Shibata Y, Takahashi H, Chiba M, Ishii Y. Prediction of hepatic clearance and availability by cryopreserved human hepatocytes: an application of serum incubation method. Drug Metab Dispos. 2002;30(8):892–6. doi:10.1124/dmd.30.8.892.
48. Hodgson E, Levi PE. Pesticides: an important but underused model for the environmental health sciences. Environ Health Perspect. 1996;104 Suppl 1:97–106. doi:10.1289/ehp.96104s197.
49. Spitzen J, Koelewijn T, Mukabana WR, Takken W. Effect of insecticide-treated bed nets on house-entry by malaria mosquitoes: The flight response recorded in a semi-field study in Kenya. Acta Trop. 2017;172:180–5. doi:10.1016/j.actatropica.2017.05.008.
50. Clark NW, Scott RC, Blain PG, Williams FM. Fate of fluazifop butyl in rat and human skin in vitro. Arch Toxicol. 1993;67(1):44–8. doi:10.1007/bf02072034.
51. Cantalamessa F. Acute toxicity of two pyrethroids, permethrin, and cypermethrin in neonatal and adult rats. Arch Toxicol. 1993;67(7):510–3. doi:10.1007/bf01969923.
52. Casida JE, Ueda K, Gaughan LC, Jao LT, Soderlund DM. Structure-biodegradability relationships in pyrethroid insecticides. Arch Environ Contam Toxicol. 1975;3(4):491–500. doi:10.1007/bf02220819.
53. Brzezinski MR, Abraham TL, Stone CL, Dean RA, Bosron WF. Purification and characterization of a human liver cocaine carboxylesterase. Biochem Pharmacol. 1994;48(9):1747–55. doi:10.1016/0006-2952(94)90461-8.
54. Durrer A, Walther B, Racciatti A, Boss G, Testa B. Structure-metabolism relationships in the hydrolysis of nicotinate esters. Pharm Res. 1991;8(7):832–9. doi:10.1023/a:1015839109449.
55. Inoue M, Morikawa M, Tsuboi M, Ito Y, Sugiura M. Comparative study of human intestinal and hepatic esterases. Jpn J Pharmacol. 1980;30(4):529–35. doi:10.1254/jjp.30.529.
56. Wikipedia contributors. Drug metabolism [Internet]. Wikipedia, The Free Encyclopedia; 2024 [cited 2024 Jul 7]. Available from: https://en.wikipedia.org/w/index.php?title=Drug_metabolism&oldid=1233160811.

According to one definition, xenobiotics are alien compounds that interfere with an organism's natural metabolism. Many xenobiotics can have a number of harmful effects if they don't have metabolism. There are several phase 1 metabolizing enzymes of xenobiotics which have capability to detoxify the toxic compounds. Several important metabolic detoxication enzymes are presented, including the mammalian microsomal cytochrome Carboxylesterases. Mammalian carboxyleterases are key enzymes from the serine hydrolase enzyme. Carboxylesterases (CEs) are usually considered as a xenobiotic metabolizing enzymes that hydrolyze esterified xenobiotics into some products of alcohol and carboxylic acid. These proteins metabolize a large number of therapeutically useful medications, which affects how well medicinal treatments work. Xenobiotics are foreign compounds that can disrupt normal metabolic processes, necessitating their detoxification through enzymatic metabolism. Human carboxylesterases (CEs), a critical class of serine hydrolases, play a key role in the hydrolysis of esterified xenobiotics into alcohol and carboxylic acid derivatives, aiding in their elimination. These enzymes, predominantly expressed in the liver and gastrointestinal tract, contribute significantly to drug metabolism, influencing therapeutic efficacy and detoxification pathways. This review explores the structure, function, and biological significance of CEs, particularly CES1 and CES2, in xenobiotic metabolism. Their role in processing pharmaceutical agents, environmental pollutants, and endogenous substrates underscores their pharmacological importance. Furthermore, interindividual variations in CE activity affect drug bioavailability and toxicity, highlighting the need for further research into CE modulators and inhibitors. Understanding the metabolic role of CEs can enhance drug development strategies and improve therapeutic interventions for xenobiotic exposure.

🔒 This is a subscription article

Full text is available to subscribers and institutional members. Please choose an option below to access it.

1. Joseph P. Transcriptomics in toxicology. Food Chem Toxicol. 2017;109(Pt 1):650–62. doi:10.1016/j.fct.2017.07.031.
2. Mansuy D. Le métabolisme des xénobiotiques: effets bénéfiques, effets néfastes. Biol Aujourd’hui. 2013;207(1):33–7. doi:10.1051/jbio/2013003.
3. Patterson AD, Gonzalez FJ, Idle JR. Xenobiotic metabolism: a view through the metabolometer. Chem Res Toxicol. 2010;23(5):851–60. doi:10.1021/tx100020p.
4. Detoxification and Substance Abuse Treatment. Treatment Improvement Protocol (TIP) Series. Rockville (MD); 2006.
5. Kreitinger JM, Beamer CA, Shepherd DM. Environmental immunology: Lessons learned from exposure to a select panel of immunotoxicants. J Immunol. 2016;196(8):3217–25. doi:10.4049/jimmunol.1502149.
6. Croom E. Metabolism of xenobiotics of human environments. Prog Mol Biol Transl Sci. 2012;112:31–88. doi:10.1016/B978-0-12-415813-9.00003-9.
7. Godin SJ, Scollon EJ, Hughes MF, Potter PM, DeVito MJ, Ross MK. Species differences in the in vitro metabolism of deltamethrin and esfenvalerate: differential oxidative and hydrolytic metabolism by humans and rats. Drug Metab Dispos. 2006;34(10):1764–71. doi:10.1124/dmd.106.010058.
8. Sterri SH, Fonnum F. The Role of Carboxylesterases in Therapeutic Intervention of Nerve Gases Poisoning. In: Handbook of Toxicology of Chemical Warfare Agents. 2015.
9. Yan B. Carboxylesterases. In: Encyclopedia of Toxicology. Elsevier; 2014. p. 695–8.
10. Bachmann K. Drug Metabolism. In: Pharmacology. Elsevier; 2009. p. 131–73.
11. Koppel N, Maini Rekdal V, Balskus EP. Chemical transformation of xenobiotics by the human gut microbiota. Science. 2017;356(6344). doi:10.1126/science.aag2770.
12. Abdelsalam NA, Ramadan AT, ElRakaiby MT, Aziz RK. Toxicomicrobiomics: The human microbiome vs. pharmaceutical, dietary, and environmental xenobiotics. Front Pharmacol. 2020;11:390. doi:10.3389/fphar.2020.00390.
13. Clarke G, Sandhu KV, Griffin BT, Dinan TG, Cryan JF, Hyland NP. Gut reactions: breaking down xenobiotic-microbiome interactions. Pharmacol Rev. 2019;71:198–224. doi:10.1124/pr.118.015768.
14. Wang D, Zou L, Jin Q, Hou J, Ge G, Yang L. Human carboxylesterases: a comprehensive review. Acta Pharm Sin B. 2018;8(5):699–712. doi:10.1016/j.apsb.2018.05.005.
15. Hatfield MJ, Umans RA, Hyatt JL, Edwards CC, Wierdl M, Tsurkan L, et al. Carboxylesterases: General detoxifying enzymes. Chem Biol Interact. 2016;259(Pt B):327–31. doi:10.1016/j.cbi.2016.02.011.
16. Sanghani SP, Sanghani PC, Schiel MA, Bosron WF. Human carboxylesterases: an update on CES1, CES2 and CES3. Protein Pept Lett. 2009;16:1207–14. doi:10.2174/092986609789071324.
17. Satoh T, Hosokawa M. Structure, function and regulation of carboxylesterases. Chem Biol Interact. 2006;162:195–211. doi:10.1016/j.cbi.2006.07.001.
18. Satoh T, Hosokawa M. The mammalian carboxylesterases: from molecules to functions. Annu Rev Pharmacol Toxicol. 1998;38:257–88. doi:10.1146/annurev.pharmtox.38.1.257.
19. Ross MK, Crow JA. Human carboxylesterases and their role in xenobiotic and endobiotic metabolism. J Biochem Mol Toxicol. 2007;21:187–96. doi:10.1002/jbt.20178.
20. Hosokawa M. Structure and catalytic properties of carboxylesterase isozymes involved in metabolic activation of prodrugs. Molecules. 2008;13:412–31. doi:10.3390/molecules13020412.
21. Imai T. Human carboxylesterase isozymes: catalytic properties and rational drug design. Drug Metab Pharmacokinet. 2006;21:173–85. doi:10.2133/dmpk.21.173.
22. Redinbo MR, Potter PM. Mammalian carboxylesterases: from drug targets to protein therapeutics. Drug Discov Today. 2005;10:313–25. doi:10.1016/S1359-6446(05)03383-0.
23. Satoh T, Taylor P, Bosron WF, Sanghani SP, Hosokawa M, La Du BN. Current progress on esterases: from molecular structure to function. Drug Metab Dispos. 2002;30:488–93. doi:10.1124/dmd.30.5.488.
24. Potter PM, Wolverton JS, Morton CL, Wierdl M, Danks MK. Cellular localization domains of a rabbit and a human carboxylesterase: influence on irinotecan (CPT-11) metabolism by the rabbit enzyme. Cancer Res. 1998;58:3627–32.
25. Zhu HJ, Wang X, Gawronski BE, Brinda BJ, Angiolillo DJ, Markowitz JS. Carboxylesterase 1 as a determinant of clopidogrel metabolism and activation. J Pharmacol Exp Ther. 2013;344:665–72. doi:10.1124/jpet.112.201640.
26. Zhu HJ, Markowitz JS. Activation of the antiviral prodrug oseltamivir is impaired by two newly identified carboxylesterase 1 variants. Drug Metab Dispos. 2009;37:264–7. doi:10.1124/dmd.108.024943.
27. Nishi K, Huang H, Kamita SG, Kim IH, Morisseau C, Hammock BD. Characterization of pyrethroid hydrolysis by the human liver carboxylesterases CES-1 and CES-2. Arch Biochem Biophys. 2006;445:115–23. doi:10.1016/j.abb.2005.11.005.
28. Imai T, Ohura K. The role of intestinal carboxylesterase in the oral absorption of prodrugs. Curr Drug Metab. 2010;11:793–805. doi:10.2174/138920010794328904.
29. Lian J, Nelson R, Lehner R. Carboxylesterases in lipid metabolism: from mouse to human. Protein Cell. 2018;9(3):178–95. doi:10.1007/s13238-017-0437-z.
30. Alam M, Ho S, Vance DE, Lehner R. Heterologous expression, purification, and characterization of human triacylglycerol hydrolase. Protein Expr Purif. 2002;24(1):33–42. doi:10.1006/prep.2001.1553.
31. Ruby MA, Massart J, Hunerdosse DM, Schönke M, Correia JC, Louie SM. Human carboxylesterase 2 reverses obesity-induced diacylglycerol accumulation and glucose intolerance. Cell Rep. 2017;18(3):636–46. doi:10.1016/j.celrep.2016.12.070.
32. Crow JA, Herring KL, Xie S, Borazjani A, Potter PM, Ross MK. Inhibition of carboxylesterase activity of THP1 monocytes/macrophages and recombinant human carboxylesterase 1 by oxysterols and fatty acids. Biochim Biophys Acta. 2010;1801(1):31–41. doi:10.1016/j.bbalip.2009.09.002.
33. Alam M, Vance DE, Lehner R. Structure-function analysis of human triacylglycerol hydrolase by site-directed mutagenesis: identification of the catalytic triad and a glycosylation site. Biochemistry. 2002;41(21):6679–87. doi:10.1021/bi0255625.
34. Wang DD, Zou LW, Jin Q, Hou J, Ge GB, Yang L. Recent progress in the discovery of natural inhibitors against human carboxylesterases. Fitoterapia. 2017;117:84–95. doi:10.1016/j.fitote.2017.01.010.
35. Dominguez E, Galmozzi A, Chang JW, Hsu KL, Pawlak J, Li W. Integrated phenotypic and activity-based profiling links Ces3 to obesity and diabetes. Nat Chem Biol. 2014;10(2):113–21. doi:10.1038/nchembio.1429.
36. Crow JA, Middleton BL, Borazjani A, Hatfield MJ, Potter PM, Ross MK. Inhibition of carboxylesterase 1 is associated with cholesteryl ester retention in human THP-1 monocyte/macrophages. Biochim Biophys Acta. 2008;1781(12):643–54. doi:10.1016/j.bbalip.2008.07.005.
37. Yoon KJP, Hyatt JL, Morton CL, Lee RE, Potter PM, Danks MK. Characterization of inhibitors of specific carboxylesterases: development of carboxylesterase inhibitors for translational application. Mol Cancer Ther. 2004;3(7):903–9.
38. Xu Y, Zhang C, He W, Liu D. Regulations of xenobiotics and endobiotics on carboxylesterases: a comprehensive review. Eur J Drug Metab Pharmacokinet. 2016;41(4):321–30. doi:10.1007/s13318-016-0326-5.
39. Hicks LD, Hyatt JL, Stoddard S, Tsurkan L, Edwards CC, Wadkins RM. Improved, selective, human intestinal carboxylesterase inhibitors designed to modulate irinotecan (CPT-11) toxicity. J Med Chem. 2009;52(12):3742–52. doi:10.1021/jm9001296.
40. Aranda J, Cerqueira NMFS, Fernandes PA, Roca M, Tuñon I, Ramos MJ. The catalytic mechanism of carboxylesterases: a computational study. Biochemistry. 2014;53(36):5820–9. doi:10.1021/bi500934j.
41. Liebler DC, Guengerich FP. Elucidating mechanisms of drug-induced toxicity. Nat Rev Drug Discov. 2005;4(5):410–20. doi:10.1038/nrd1720.
42. Chambers JP, Hartgraves SL, Murphy MR, Wayner MJ, Kumar N, Valdes JJ. Effects of three reputed carboxylesterase inhibitors upon rat serum esterase activity. Neurosci Biobehav Rev. 1991;15(1):85–8. doi:10.1016/s0149-7634(05)80096-x.
43. Cashman JR, Perotti BY, Berkman CE, Lin J. Pharmacokinetics and molecular detoxication. Environ Health Perspect. 1996;104 Suppl 1:23–40. doi:10.1289/ehp.96104s123.
44. Jones RD, Taylor AM, Tong EY, Repa JJ. Carboxylesterases are uniquely expressed among tissues and regulated by nuclear hormone receptors in the mouse. Drug Metab Dispos. 2013;41(1):40–9. doi:10.1124/dmd.112.048397.
45. Ross MK, Crow JA. Human carboxylesterases and their role in xenobiotic and endobiotic metabolism. J Biochem Mol Toxicol. 2007;21(4):187–96. doi:10.1002/jbt.20178.
46. Tsujita T, Okuda H. The synthesis of fatty acid ethyl ester by carboxylester lipase. Eur J Biochem. 1994;224(1):57–62. doi:10.1111/j.1432-1033.1994.tb19994.x.
47. Shibata Y, Takahashi H, Chiba M, Ishii Y. Prediction of hepatic clearance and availability by cryopreserved human hepatocytes: an application of serum incubation method. Drug Metab Dispos. 2002;30(8):892–6. doi:10.1124/dmd.30.8.892.
48. Hodgson E, Levi PE. Pesticides: an important but underused model for the environmental health sciences. Environ Health Perspect. 1996;104 Suppl 1:97–106. doi:10.1289/ehp.96104s197.
49. Spitzen J, Koelewijn T, Mukabana WR, Takken W. Effect of insecticide-treated bed nets on house-entry by malaria mosquitoes: The flight response recorded in a semi-field study in Kenya. Acta Trop. 2017;172:180–5. doi:10.1016/j.actatropica.2017.05.008.
50. Clark NW, Scott RC, Blain PG, Williams FM. Fate of fluazifop butyl in rat and human skin in vitro. Arch Toxicol. 1993;67(1):44–8. doi:10.1007/bf02072034.
51. Cantalamessa F. Acute toxicity of two pyrethroids, permethrin, and cypermethrin in neonatal and adult rats. Arch Toxicol. 1993;67(7):510–3. doi:10.1007/bf01969923.
52. Casida JE, Ueda K, Gaughan LC, Jao LT, Soderlund DM. Structure-biodegradability relationships in pyrethroid insecticides. Arch Environ Contam Toxicol. 1975;3(4):491–500. doi:10.1007/bf02220819.
53. Brzezinski MR, Abraham TL, Stone CL, Dean RA, Bosron WF. Purification and characterization of a human liver cocaine carboxylesterase. Biochem Pharmacol. 1994;48(9):1747–55. doi:10.1016/0006-2952(94)90461-8.
54. Durrer A, Walther B, Racciatti A, Boss G, Testa B. Structure-metabolism relationships in the hydrolysis of nicotinate esters. Pharm Res. 1991;8(7):832–9. doi:10.1023/a:1015839109449.
55. Inoue M, Morikawa M, Tsuboi M, Ito Y, Sugiura M. Comparative study of human intestinal and hepatic esterases. Jpn J Pharmacol. 1980;30(4):529–35. doi:10.1254/jjp.30.529.
56. Wikipedia contributors. Drug metabolism [Internet]. Wikipedia, The Free Encyclopedia; 2024 [cited 2024 Jul 7]. Available from: https://en.wikipedia.org/w/index.php?title=Drug_metabolism&oldid=1233160811.