{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T22:11:09Z","timestamp":1768687869674,"version":"3.49.0"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T00:00:00Z","timestamp":1604275200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T00:00:00Z","timestamp":1604275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773815"],"award-info":[{"award-number":["81773815"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81922070"],"award-info":[{"award-number":["81922070"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Drug Metab Pharmacokinet"],"published-print":{"date-parts":[[2021,1]]},"DOI":"10.1007\/s13318-020-00659-9","type":"journal-article","created":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T17:03:14Z","timestamp":1604336594000},"page":"129-139","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Rapalogues as hCES2A Inhibitors: In Vitro and In Silico Investigations"],"prefix":"10.1007","volume":"46","author":[{"given":"Cheng-Cheng","family":"Shi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun-Qing","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong-Jing","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Qing","family":"Guan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Lin","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi-Tong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng-Ru","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9670-4349","authenticated-orcid":false,"given":"Guang-Bo","family":"Ge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Rong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,11,2]]},"reference":[{"issue":"7","key":"659_CR1","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1097\/00007890-200110150-00001","volume":"72","author":"BD Kahan","year":"2001","unstructured":"Kahan BD, Camardo JS. Rapamycin: clinical results and future opportunities. Transplantation. 2001;72(7):1181\u201393. https:\/\/doi.org\/10.1097\/00007890-200110150-00001.","journal-title":"Transplantation"},{"issue":"10","key":"659_CR2","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1038\/aps.2015.68","volume":"36","author":"LH Meng","year":"2015","unstructured":"Meng LH, Zheng XF. Toward rapamycin analog (rapalog)-based precision cancer therapy. Acta Pharmacol Sin. 2015;36(10):1163\u20139. https:\/\/doi.org\/10.1038\/aps.2015.68.","journal-title":"Acta Pharmacol Sin."},{"issue":"4","key":"659_CR3","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1158\/1078-0432.CCR-08-0889","volume":"15","author":"E Pencreach","year":"2009","unstructured":"Pencreach E, Gu\u00e9rin E, Nicolet C, Lelong-Rebel I, Voegeli AC, Oudet P, Larsen AK, Gaub MP, Guenot D. Marked activity of irinotecan and rapamycin combination toward colon cancer cells in vivo and in vitro is mediated through cooperative modulation of the mammalian target of rapamycin\/hypoxia-inducible factor-1alpha axis. Clin Cancer Res. 2009;15(4):1297\u2013307. https:\/\/doi.org\/10.1158\/1078-0432.CCR-08-0889.","journal-title":"Clin Cancer Res."},{"issue":"5","key":"659_CR4","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.1016\/j.transproceed.2008.03.152","volume":"40","author":"H Pan","year":"2008","unstructured":"Pan H, Wang L, Zhang X, Zhang G, Mai H, Han Y, Guo S. Rapamycin, mycophenolate mofetil, methylprednisolone, and cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin-based conditioning regimen to induce partial tolerance to hind limb allografts without cytoreductive conditioning. Transplant Proc. 2008;40(5):1714\u201321. https:\/\/doi.org\/10.1016\/j.transproceed.2008.03.152.","journal-title":"Transplant Proc."},{"issue":"9","key":"659_CR5","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1124\/dmd.107.014746","volume":"35","author":"P Cai","year":"2007","unstructured":"Cai P, Tsao RS, Ruppen ME. In vitro metabolic study of temsirolimus: preparation, isolation, and identification of the metabolites. Drug Metab Dispos. 2007;35(9):1554\u201363. https:\/\/doi.org\/10.1124\/dmd.107.014746.","journal-title":"Drug Metab Dispos."},{"issue":"3","key":"659_CR6","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1124\/jpet.106.110577","volume":"319","author":"M Tang","year":"2006","unstructured":"Tang M, Mukundan M, Yang J, Charpentier N, LeCluyse EL, Black C, Yang DF, Shi DS, Yan BF. Antiplatelet agents aspirin and clopidogrel are hydrolyzed by distinct carboxylesterases, and clopidogrel is transesterificated in the presence of ethyl alcohol. J Pharmacol Exp Ther. 2006;319(3):1467\u201376. https:\/\/doi.org\/10.1124\/jpet.106.110577.","journal-title":"J Pharmacol Exp Ther."},{"issue":"7","key":"659_CR7","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1016\/j.bcp.2008.12.017","volume":"77","author":"HJ Zhu","year":"2009","unstructured":"Zhu HJ, Appel DI, Johnson JA, Chavin KD, Markowitz JS. Role of carboxylesterase 1 and impact of natural genetic variants on the hydrolysis of trandolapril. Biochem Pharmacol. 2009;77(7):1266\u201372. https:\/\/doi.org\/10.1016\/j.bcp.2008.12.017.","journal-title":"Biochem Pharmacol."},{"key":"659_CR8","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.jpba.2019.02.004","volume":"168","author":"ZW Li","year":"2019","unstructured":"Li ZW, Zhang J, Zhang YF, Zuo Z. Role of esterase mediated hydrolysis of simvastatin in human and rat blood and its impact on pharmacokinetic profiles of simvastatin and its active metabolite in rat. J Pharm Biomed Anal. 2019;168:13\u201322. https:\/\/doi.org\/10.1016\/j.jpba.2019.02.004.","journal-title":"J Pharm Biomed Anal."},{"issue":"3","key":"659_CR9","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1124\/jpet.106.111807","volume":"319","author":"DS Shi","year":"2006","unstructured":"Shi DS, Yang J, Yang DF, LeCluyse EL, Black C, You L, Akhlaghi F, Yan B. Anti-influenza prodrug oseltamivir is activated by carboxylesterase human carboxylesterase 1, and the activation is inhibited by antiplatelet agent clopidogrel. J Pharmacol Exp Ther. 2006;319(3):1477\u201384. https:\/\/doi.org\/10.1124\/jpet.106.111807.","journal-title":"J Pharmacol Exp Ther."},{"issue":"1","key":"659_CR10","doi-asserted-by":"publisher","first-page":"41","DOI":"10.2174\/0929867033368619","volume":"10","author":"MK Ma","year":"2003","unstructured":"Ma MK, McLeod HL. Lessons learned from the irinotecan metabolic pathway. Curr Med Chem. 2003;10(1):41\u20139. https:\/\/doi.org\/10.2174\/0929867033368619.","journal-title":"Curr Med Chem."},{"issue":"12","key":"659_CR11","doi-asserted-by":"publisher","first-page":"2210","DOI":"10.1124\/dmd.110.034249","volume":"38","author":"N Fujiyama","year":"2010","unstructured":"Fujiyama N, Miura M, Kato S, Sone T, Isobe M, Satoh S. Involvement of carboxylesterase 1 and 2 in the hydrolysis of mycophenolate mofetil. Drug Metab Dispos. 2010;38(12):2210\u20137. https:\/\/doi.org\/10.1124\/dmd.110.034249.","journal-title":"Drug Metab Dispos."},{"issue":"2","key":"659_CR12","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1124\/jpet.104.067116","volume":"310","author":"ZJ Sun","year":"2004","unstructured":"Sun ZJ, Murry DJ, Sanghani SP, Davis WI, Kedishvili NY, Zou Q, Hurley TD, Bosron WF. Methylphenidate is stereoselectively hydrolyzed by human carboxylesterase CES1A1. J Pharmacol Exp Ther. 2004;310(2):469\u201376. https:\/\/doi.org\/10.1124\/jpet.104.067116.","journal-title":"J Pharmacol Exp Ther."},{"issue":"1","key":"659_CR13","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.bcp.2010.09.001","volume":"81","author":"MJ Hatfield","year":"2011","unstructured":"Hatfield MJ, Tsurkan L, Garrett M, Shaver TM, Hyatt JL, Edwards CC, Hicks LD, Potter PM. Organ-specific carboxylesterase profiling identifies the small intestine and kidney as major contributors of activation of the anticancer prodrug CPT-11. Biochem Pharmacol. 2011;81(1):24\u201331. https:\/\/doi.org\/10.1016\/j.bcp.2010.09.001.","journal-title":"Biochem Pharmacol"},{"issue":"2","key":"659_CR14","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1021\/jm7011479","volume":"51","author":"BL Barthel","year":"2008","unstructured":"Barthel BL, Torres RC, Hyatt JL, Edwards CC, Hatfield MJ, Potter PM, Koch TH. Identification of human intestinal carboxylesterase as the primary enzyme for activation of a doxazolidine carbamate prodrug. J Med Chem. 2008;51(2):298\u2013304. https:\/\/doi.org\/10.1021\/jm7011479.","journal-title":"J Med Chem"},{"issue":"2","key":"659_CR15","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.bcp.2008.10.005","volume":"77","author":"DF Yang","year":"2009","unstructured":"Yang DF, Pearce RE, Wang XL, Gaedigk R, Wan YJY, Yan BF. Human carboxylesterases HCE1 and HCE2: ontogenic expression, inter-individual variability and differential hydrolysis of oseltamivir, aspirin, deltamethrin and permethrin. Biochem Pharmacol. 2009;77(2):238\u201347. https:\/\/doi.org\/10.1016\/j.bcp.2008.10.005.","journal-title":"Biochem Pharmacol."},{"issue":"51","key":"659_CR16","doi-asserted-by":"publisher","first-page":"28474","DOI":"10.1021\/acsami.5b09573","volume":"7","author":"Q Jin","year":"2015","unstructured":"Jin Q, Feng L, Wang DD, Dai ZR, Wang P, Zou LW, Liu ZH, Wang JY, Yu Y, Ge GB, Cui JN, Yang L. A two-photon ratiometric fluorescent probe for imaging carboxylesterase 2 in living cells and tissues. ACS Appl Mater Interfaces. 2015;7(51):28474\u201381. https:\/\/doi.org\/10.1021\/acsami.5b09573.","journal-title":"ACS Appl Mater Interfaces"},{"key":"659_CR17","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.ijbiomac.2019.06.235","volume":"137","author":"YQ Song","year":"2019","unstructured":"Song YQ, Guan XQ, Weng ZM, Wang YQ, Chen J, Jin Q, Fang SQ, Fan B, Cao YF, Hou J, Ge GB. Discovery of a highly specific and efficacious inhibitor of human carboxylesterase 2 by large-scale screening. Int J Biol Macromol. 2019;137:261\u20139. https:\/\/doi.org\/10.1016\/j.ijbiomac.2019.06.235.","journal-title":"Int J Biol Macromol"},{"issue":"15","key":"659_CR18","doi-asserted-by":"publisher","first-page":"3183","DOI":"10.1039\/c5cc09874b","volume":"52","author":"DD Wang","year":"2016","unstructured":"Wang DD, Jin Q, Zou LW, Hou J, Lv X, Lei W, Cheng HL, Ge GB, Yang L. A bioluminescent sensor for highly selective and sensitive detection of human carboxylesterase 1 in complex biological samples. Chem Commun. 2016;52(15):3183\u20136. https:\/\/doi.org\/10.1039\/c5cc09874b.","journal-title":"Chem Commun."},{"key":"659_CR19","doi-asserted-by":"publisher","first-page":"1944","DOI":"10.1016\/j.ijbiomac.2018.09.178","volume":"120","author":"YQ Wang","year":"2018","unstructured":"Wang YQ, Weng ZM, Dou TY, Hou J, Wang DD, Ding LL, Zou LW, Yu Y, Chen J, Tang H, Ge GB. Nevadensin is a naturally occurring selective inhibitor of human carboxylesterase 1. Int J Biol Macromol. 2018;120:1944\u201354. https:\/\/doi.org\/10.1016\/j.ijbiomac.2018.09.178.","journal-title":"Int J Biol Macromol."},{"key":"659_CR20","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.bioorg.2018.01.011","volume":"77","author":"ZM Weng","year":"2018","unstructured":"Weng ZM, Ge GB, Dou TY, Wang P, Liu PK, Tian XH, Qiao N, Yu Y, Zou LW, Zhou Q, Zhang WD, Hou J. Characterization and structure\u2013activity relationship studies of flavonoids as inhibitors against human carboxylesterase 2. Bioorg Chem. 2018;77:320\u20139. https:\/\/doi.org\/10.1016\/j.bioorg.2018.01.011.","journal-title":"Bioorg Chem."},{"issue":"8","key":"659_CR21","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1124\/dmd.111.039628","volume":"39","author":"J Wang","year":"2011","unstructured":"Wang J, Williams ET, Bourgea J, Wong YN, Patten CJ. Characterization of recombinant human carboxylesterases: fluorescein diacetate as a probe substrate for human carboxylesterase 2. Drug Metab Dispos. 2011;39(8):1329\u201333. https:\/\/doi.org\/10.1124\/dmd.111.039628.","journal-title":"Drug Metab Dispos."},{"issue":"11","key":"659_CR22","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.1124\/dmd.107.015727","volume":"35","author":"C Jewell","year":"2007","unstructured":"Jewell C, Ackermann C, Payne NA, Fate G, Voorman R, Williams FM. Specificity of procaine and ester hydrolysis by human, minipig, and rat skin and liver. Drug Metab Dispos. 2007;35(11):2015\u201322. https:\/\/doi.org\/10.1124\/dmd.107.015727.","journal-title":"Drug Metab Dispos."},{"key":"659_CR23","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/0006-2952(61)90145-9","volume":"7","author":"GL Ellman","year":"1961","unstructured":"Ellman GL, Courtney KD, Andres V, Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961;7:88\u201395. https:\/\/doi.org\/10.1016\/0006-2952(61)90145-9.","journal-title":"Biochem Pharmacol."},{"key":"659_CR24","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/10.1016\/j.cbi.2019.06.003","volume":"308","author":"YQ Song","year":"2019","unstructured":"Song YQ, Weng ZM, Dou TY, Finel M, Wang YQ, Ding LL, Jin Q, Wang DD, Fang SQ, Cao YF, Hou J, Ge GB. Inhibition of human carboxylesterases by magnolol: kinetic analyses and mechanism. Chem Biol Interact. 2019;308:339\u201349. https:\/\/doi.org\/10.1016\/10.1016\/j.cbi.2019.06.003.","journal-title":"Chem Biol Interact."},{"issue":"2","key":"659_CR25","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/jcc.21334","volume":"31","author":"O Trott","year":"2010","unstructured":"Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31(2):455\u201361. https:\/\/doi.org\/10.1002\/jcc.21334.","journal-title":"J Comput Chem."},{"key":"659_CR26","doi-asserted-by":"publisher","first-page":"W296","DOI":"10.1093\/nar\/gky427","volume":"46","author":"A Waterhouse","year":"2018","unstructured":"Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, Heer FT, de Beer TAP, Rempfer C, Bordoli L, Lepore R, Schwede T. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res. 2018;46:W296\u2013303. https:\/\/doi.org\/10.1093\/nar\/gky427.","journal-title":"Nucleic Acids Res"},{"key":"659_CR27","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.ejmech.2016.02.020","volume":"112","author":"LW Zou","year":"2016","unstructured":"Zou LW, Li YG, Wang P, Zhou K, Hou J, Jin Q, Hao DC, Ge GB, Yang L. Design, synthesis, and structure\u2013activity relationship study of glycyrrhetinic acid derivatives as potent and selective inhibitors against human carboxylesterase 2. Eur J Med Chem. 2016;112:280\u20138. https:\/\/doi.org\/10.1016\/j.ejmech.2016.02.020.","journal-title":"Eur J Med Chem."},{"issue":"1","key":"659_CR28","first-page":"57","volume":"17","author":"MF Sanner","year":"1999","unstructured":"Sanner MF. Python: a programming language for software integration and development. J Mol Graph Model. 1999;17(1):57\u201361.","journal-title":"J Mol Graph Model."},{"issue":"16","key":"659_CR29","doi-asserted-by":"publisher","first-page":"2785","DOI":"10.1002\/jcc.21256","volume":"30","author":"GM Morris","year":"2009","unstructured":"Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem. 2009;30(16):2785\u201391. https:\/\/doi.org\/10.1002\/jcc.21256.","journal-title":"J Comput Chem."},{"key":"659_CR30","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.molstruc.2018.09.051","volume":"1177","author":"N Askari","year":"2019","unstructured":"Askari N, Rezvannejad E, Moghadam SD, Shafieipour S. Structural analysis of misfolding equilibrative nucleoside transporter 3in H-syndrome. J Mol Struct. 2019;1177:177\u201385. https:\/\/doi.org\/10.1016\/j.molstruc.2018.09.051.","journal-title":"J Mol Struct."},{"key":"659_CR31","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.molstruc.2018.04.010","volume":"1166","author":"KM El-Gamal","year":"2018","unstructured":"El-Gamal KM, El-Morsy AM, Saad AM, Eissa IH, Alswah M. Synthesis, docking, QSAR, ADMET and antimicrobial evaluation of new quinoline-3-carbonitrile derivatives as potential DNA-gyrase inhibitors. J Mol Struct. 2018;1166:15\u201333. https:\/\/doi.org\/10.1016\/j.molstruc.2018.04.010.","journal-title":"J Mol Struct."},{"issue":"6","key":"659_CR32","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1093\/jnci\/86.6.446","volume":"86","author":"D Abigerges","year":"1994","unstructured":"Abigerges D, Armand JP, Chabot GG, Da Costa L, Fadel E, Cote C, H\u00e9rait P, Gandia D. Irinotecan (CPT-11) high-dose escalation using intensive high-dose loperamide to control diarrhea. J Natl Cancer Inst. 1994;86(6):446\u20139. https:\/\/doi.org\/10.1093\/jnci\/86.6.446.","journal-title":"J Natl Cancer Inst."},{"issue":"7","key":"659_CR33","doi-asserted-by":"publisher","first-page":"3626","DOI":"10.1039\/c9ra09203j","volume":"10","author":"CC Shi","year":"2020","unstructured":"Shi CC, Chen TR, Zhang QH, Wei LH, Huang C, Zhu YD, Liu HB, Bai YK, Wang FJ, Guo WZ, Zhang LR, Ge GB. Inhibition of human thrombin by the constituents of licorice: inhibition kinetics and mechanistic insights through in vitro and in silico studies. RSC Adv. 2020;10(7):3626\u201335. https:\/\/doi.org\/10.1039\/c9ra09203j.","journal-title":"RSC Adv."},{"issue":"3","key":"659_CR34","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1007\/s00280-013-2230-x","volume":"72","author":"IS Kim","year":"2013","unstructured":"Kim IS, Kim Y, Kwak TH, Yoo HH. Effects of beta-lapachone, a new anticancer candidate, on cytochrome P450-mediated drug metabolism. Cancer Chemother Pharmacol. 2013;72(3):699\u2013702. https:\/\/doi.org\/10.1007\/s00280-013-2230-x.","journal-title":"Cancer Chemother Pharmacol."},{"issue":"6","key":"659_CR35","doi-asserted-by":"publisher","first-page":"2188","DOI":"10.1002\/hep.25961","volume":"56","author":"AD Quiroga","year":"2012","unstructured":"Quiroga AD, Li LN, Tr\u00f6tzm\u00fcller M, Nelson R, Proctor SD, K\u00f6feler H, Lehner R. Deficiency of carboxylesterase 1\/esterase-x results in obesity, hepatic steatosis, and hyperlipidemia. Hepatology. 2012;56(6):2188\u201398. https:\/\/doi.org\/10.1002\/hep.25961.","journal-title":"Hepatology"},{"issue":"2","key":"659_CR36","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1038\/nchembio.1429","volume":"10","author":"E Dominguez","year":"2014","unstructured":"Dominguez E, Galmozzi A, Chang JW, Hsu KL, Pawlak J, Li WW, Godio C, Thomas J, Partida D, Niessen S, O\u2019Brien PE, Russell AP, Watt MJ, Nomura DK, Cravatt BF, Saez E. Integrated phenotypic and activity-based profiling links Ces3 to obesity and diabetes. Nat Chem Biol. 2014;10(2):113\u201321. https:\/\/doi.org\/10.1038\/nchembio.1429.","journal-title":"Nat Chem Biol."},{"issue":"1","key":"659_CR37","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.annemergmed.2016.03.047","volume":"69","author":"W Eggleston","year":"2017","unstructured":"Eggleston W, Clark KH, Marraffa JM. Loperamide abuse associated with cardiac dysrhythmia and death. Ann Emerg Med. 2017;69(1):83\u20136. https:\/\/doi.org\/10.1016\/j.annemergmed.2016.03.047.","journal-title":"Ann Emerg Med."},{"key":"659_CR38","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.fitote.2017.01.010","volume":"117","author":"DD Wang","year":"2017","unstructured":"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\u201395. https:\/\/doi.org\/10.1016\/j.fitote.2017.01.010.","journal-title":"Fitoterapia"},{"issue":"61","key":"659_CR39","doi-asserted-by":"publisher","first-page":"35904","DOI":"10.1039\/c9ra07457k","volume":"9","author":"LX Ding","year":"2019","unstructured":"Ding LX, Wang L, Zou K, Li B, Song YQ, Zhang QH, Zhao YT, Xu ZJ, Ge GB, Zhao B, Zhu WL. Discovery of dihydrooxazolo[2,3-a]isoquinoliniums as highly specific inhibitors of hCE2. RSC Adv. 2019;9(61):35904\u201312. https:\/\/doi.org\/10.1039\/c9ra07457k.","journal-title":"RSC Adv."},{"issue":"5","key":"659_CR40","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1124\/dmd.108.024331","volume":"37","author":"S Takahashi","year":"2009","unstructured":"Takahashi S, Katoh M, Saitoh T, Nakajima M, Yokoi T. Different inhibitory effects in rat and human carboxylesterases. Drug Metab Dispos. 2009;37(5):956\u201361. https:\/\/doi.org\/10.1124\/dmd.108.024331.","journal-title":"Drug Metab Dispos."},{"issue":"12","key":"659_CR41","doi-asserted-by":"publisher","first-page":"5434","DOI":"10.1002\/jps.21376","volume":"97","author":"S Takahashi","year":"2008","unstructured":"Takahashi S, Katoh M, Saitoh T, Nakajima M, Yokoi T. Allosteric kinetics of human carboxylesterase 1: species differences and interindividual variability. J Pharm Sci. 2008;97(12):5434\u201345. https:\/\/doi.org\/10.1002\/jps.21376.","journal-title":"J Pharm Sci."},{"issue":"10","key":"659_CR42","doi-asserted-by":"publisher","first-page":"1764","DOI":"10.1124\/dmd.106.010058","volume":"34","author":"SJ Godin","year":"2006","unstructured":"Godin SJ, Scollon EJ, Hughes MF, Potter PM, De VMJ, 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\u201371. https:\/\/doi.org\/10.1124\/dmd.106.010058.","journal-title":"Drug Metab Dispos."},{"issue":"14","key":"659_CR43","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.2165\/00003088-200342140-00006","volume":"42","author":"G Scott","year":"2003","unstructured":"Scott G, Osborne SA, Greig G, Hartmann S, Ebelin ME, Burtin P, Rappersberger K, Komar M, Wolff K. Pharmacokinetics of pimecrolimus, a novel nonsteroid anti-inflammatory drug, after single and multiple oral administration. Clin Pharmacokinet. 2003;42(14):1305\u201314. https:\/\/doi.org\/10.2165\/00003088-200342140-00006.","journal-title":"Clin Pharmacokinet."},{"issue":"5","key":"659_CR44","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1124\/dmd.105.007732","volume":"34","author":"M Zollinger","year":"2006","unstructured":"Zollinger M, Waldmeier F, Hartmann S, Zenke G, Zimmerlin AG, Glaenzel U, Baldeck JP, Schweitzer A, Berthier S, Moenius T, Grassberger MA. Pimecrolimus: absorption, distribution, metabolism, and excretion in healthy volunteers after a single oral dose and supplementary investigations in vitro. Drug Metab Dispos. 2006;34(5):765\u201374. https:\/\/doi.org\/10.1124\/dmd.105.007732.","journal-title":"Drug Metab Dispos"},{"issue":"17","key":"659_CR45","doi-asserted-by":"publisher","first-page":"4785","DOI":"10.1158\/1078-0432.CCR-12-0110","volume":"18","author":"EEW Cohen","year":"2012","unstructured":"Cohen EEW, Wu KH, Hartford C, Kocherginsky M, Eaton KN, Zha YY, Nallari A, Maitland ML, Fox-Kay K, Moshier K, House L, Ramirez J, Undevia SD, Fleming GF, Gajewski TF, Ratain MJ. Phase I studies of sirolimus alone or in combination with pharmacokinetic modulators in advanced cancer patients. Clin Cancer Res. 2012;18(17):4785\u201393. https:\/\/doi.org\/10.1158\/1078-0432.CCR-12-0110.","journal-title":"Clin Cancer Res."},{"issue":"12","key":"659_CR46","doi-asserted-by":"publisher","first-page":"2874","DOI":"10.1002\/chem.200801656","volume":"15","author":"SV Ley","year":"2009","unstructured":"Ley SV, Tackett MN, Maddess ML, Anderson JC, Brennan PE, Cappi MW, Heer JP, Helgen C, Kori M, Kouklovsky C, Marsden P, Norman J, Osborn DP, Palomero MA, Pavey JBJ, Pinel C, Robinson LA, Schnaubelt J, Scott JS, Spilling CD, Watanabe H, Wesson KE, Willis MC. Total synthesis of rapamycin. Chem Eur J. 2009;15(12):2874\u2013914. https:\/\/doi.org\/10.1002\/chem.200801656.","journal-title":"Chem Eur J"}],"container-title":["European Journal of Drug Metabolism and Pharmacokinetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s13318-020-00659-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s13318-020-00659-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s13318-020-00659-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,17]],"date-time":"2021-01-17T17:06:41Z","timestamp":1610903201000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s13318-020-00659-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,2]]},"references-count":46,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["659"],"URL":"https:\/\/doi.org\/10.1007\/s13318-020-00659-9","relation":{},"ISSN":["0378-7966","2107-0180"],"issn-type":[{"value":"0378-7966","type":"print"},{"value":"2107-0180","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,2]]},"assertion":[{"value":"2 November 2020","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This work was partially funded by the National Natural Science Foundation of China (81922070 & 81773815).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"Cheng-Cheng Shi, Yun-Qing Song, Rong-Jing He, Xiao-Qing Guan, Li-Lin Song, Shi-Tong Chen, Meng-Ru Sun, Guang-Bo Ge and Li-Rong Zhang declare that there is no conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"LZ and GG conceived the study and designed the experimental process. CS, YS, MS, LS and XG performed the experiments; CS, SC, RH, GG and LZ carried out data and results analysis; GG, LZ and CS wrote the manuscript and interpretation of data.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 contributions"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All authors approve the publication of this study.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Not applicable.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability"}},{"value":"Not applicable.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of data and material"}}]}}