高级检索

催化酰胺类药物水解代谢酶的研究进展

王誉晓, 王新鸿, 王丽梅, 邱志霞

王誉晓,王新鸿,王丽梅,等. 催化酰胺类药物水解代谢酶的研究进展[J]. 中国药科大学学报,2025,56(2):244 − 251. DOI: 10.11665/j.issn.1000-5048.2024101203
引用本文: 王誉晓,王新鸿,王丽梅,等. 催化酰胺类药物水解代谢酶的研究进展[J]. 中国药科大学学报,2025,56(2):244 − 251. DOI: 10.11665/j.issn.1000-5048.2024101203
WANG Yuxiao, WANG Xinhong, WANG Limei, et al. Research progress of hydrolases catalyzing amide drugs[J]. J China Pharm Univ, 2025, 56(2): 244 − 251. DOI: 10.11665/j.issn.1000-5048.2024101203
Citation: WANG Yuxiao, WANG Xinhong, WANG Limei, et al. Research progress of hydrolases catalyzing amide drugs[J]. J China Pharm Univ, 2025, 56(2): 244 − 251. DOI: 10.11665/j.issn.1000-5048.2024101203

催化酰胺类药物水解代谢酶的研究进展

基金项目: 国家自然科学基金项目(No.82274013)
详细信息
    通讯作者:

    邱志霞: Tel:13813983364 E-mail:qiuzhixia_cpu@163.com

  • 中图分类号: R969.1

Research progress of hydrolases catalyzing amide drugs

Funds: This study was supported by the National Natural Science Foundation of China (No.82274013)
  • 摘要:

    酰胺键是将分子中的氨基和羧基脱水缩合形成的分子键,其在药物结构设计中较为常见。酰胺键的稳定性受到多种因素的影响,使得酰胺类药物的药代动力学行为呈明显的代谢异质性。本文围绕酰胺类药物的药代动力学行为,提出水解酶在机体空间的表达和活性可能是引起酰胺类药物的药代动力学存在种属差异的重要原因之一,并归纳常见的水解酰胺类药物的酶或蛋白,为酰胺类药物的结构设计及临床研究提供参考;提出体外评价体系选择不当可能是导致药物药代动力学特征出现体内-体外不一致性的重要原因,总结目前用于评价药物体外代谢体系,为药物临床前评价提供参考。

    Abstract:

    Amide bond is formed by dehydration and condensation of amino and carboxyl groups in a molecule, which is used in structural design of drugs. The stability of the amide bond is affected by many factors, which make the pharmacokinetic behaviors of amide drugs complicated by metabolic heterogeneity. This review proposes that the expression and activity of hydrolase may be one of the important reasons for the obvious differences in the pharmacokinetics of amides among species, summarizes the common metabolic enzymes or proteins responsible for hydrolyzing amides so as to provide some reference for the structural design and further clinical study of amide drugs, and suggests that improper selection of in vitro evaluation systems may be an important cause for the inconsistency between between in vitro and in vivo pharmacokinetic characteristics of drugs, with a summary of the currently used in vitro drug metabolism systems for drug evaluation, aiming to provide a basis for preclinical evaluation of drugs.

  • 表  1   催化酰胺水解酶系总结

    表达部位 底 物 抑制剂 参考文献
    CES1 肝、肺、脂肪 4-硝基苯乙酸酯,对硝基苯酚乙酸酯(PNPA),D-荧光素甲酯,哌醋甲酯(MPH),利多卡因,可卡因,氯吡格雷,奥司他韦,咪达普利 双-(4-硝基苯基)磷酸(BNPP),苯基甲基磺酰氟化物(PMSF),洋地黄皂苷,辛伐他汀,阿立哌唑,奋乃静,硫利达嗪,氟西汀,替米沙坦 [10, 15, 1921, 29, 7072]
    CES2 小肠、肾、肝 4-硝基苯乙酸酯,PNPA,荧光素双醋酸,伊立替康,普鲁卡因,氟他胺 BNPP,PMSF,地尔硫䓬,维拉帕米,辛伐他汀,替米沙坦,毒扁豆碱,长春碱 [10, 15, 21, 29, 70, 73]
    AADAC 肠道、肝、肾 4-硝基苯乙酸酯,PNPA,非那西丁,利福霉素,氟他胺,酮康唑,茚地普隆 BNPP,PMSF,长春碱,替米沙坦,毒扁豆碱 [10, 15, 27, 31, 70, 73]
    BChE 肝、血液、肠道 可卡因,班布特罗,伊立替康,美维库铵,琥珀酰胆碱 毒扁豆碱,四异丙基焦磷酸亚胺(iso-OMPA),他克林,贝那替嗪、苯丙胺,他汀类药物 [10, 74]
    Cathepsin B 组织 a 氟甲基酮,洛昔他汀,氮嘧啶肽,寡核苷酸 [75]
    AO 肝、肾、肺 卡巴折伦,O6-苄基鸟嘌呤,酞嗪,扎来普隆 雷洛昔芬,甲萘醌,β-雌二醇 [12]
    FAAH 肠道 内源性大麻素,N-花生四烯酰乙醇酰胺,2-花生四烯酸甘油(2-AG),棕榈酰乙醇酰胺(PEA),油酰胺,油酰乙醇酰胺 b [13]
    血浆蛋白 血浆 环磷酰胺,烟酸酯,硝基乙酰苯胺,α/β-萘乙酸酯,阿司匹林,酮洛芬葡萄糖醛酸酯 地西泮,棕榈酸 [51]
    CES1:羧酸酯酶1; CES2:羧酸酯酶2; AADAC:芳香乙酰胺脱乙酰基酶; BChE:丁酰胆碱酯酶; Cathepsin B:组织蛋白酶B; AO:醛氧化酶; FAAH:脂肪酰胺水解酶; —a:底物常以特定酰胺键(肽键)结构显示; —b:目前暂未发现抑制剂药物
    下载: 导出CSV

    表  2   肝肠体外研究体系或方法汇总

    代谢部位 研究体系或方法 优 势 局 限 参考文献
    肝脏 肝微粒体、胞浆、S9 制备容易,操作简单 体系酶缺失,与体内代谢相差较大 [5456]
    肝细胞 一定程度保留肝脏功能 制备技术及培养条件复杂 [5859]
    类器官技术 模拟肝脏发育以及肝脏疾病的发生 培育周期较长,可重复性、均一性较低 [6061]
    离体肝灌流法 具有肝脏正常生理活性和生化功能,排除其他器官干扰 技术和设备要求较高 [6263]
    肝切片法 保留器官的组织结构和细胞结构,更好反应药物在体内的代谢 [64]
    肠道 肠微粒体、胞浆、S9 制备较容易,操作简单 代谢酶类少,易失活,研究结果与体内代谢相差较大 [65]
    肠细胞 基本保留了肠黏膜上皮细胞中代谢酶的活性 制备产量低,存活时间有限,代谢酶活性比肠黏膜低 [17, 28, 6667]
    类器官技术 模仿真实肠道器官的特征 培育周期较长,可重复性、均一性较低 [68]
    冷冻肠黏膜系统 保留肠黏膜上皮细胞及黏膜的代谢酶 制备技术复杂 [6768]
    肠切片法 保留器官的组织结构和细胞结构,更好反应药物在体内的代谢 技术和设备要求较高 [65]
    下载: 导出CSV
  • [1]

    Husain A, Monga J, Narwal S, et al. Prodrug rewards in medicinal chemistry: an advance and challenges approach for drug designing[J]. Chem Biodivers, 2023, 20(11): e202301169. doi: 10.1002/cbdv.202301169

    [2]

    Mckertish CM, Kayser V. A novel dual-payload ADC for the treatment of HER2+ breast and colon cancer[J]. Pharmaceutics, 2023, 15(8): 2020. doi: 10.3390/pharmaceutics15082020

    [3]

    Ichikawa T, Yamada T, Treiber A, et al. Cross-species comparison of the metabolism and excretion of selexipag[J]. Xenobiotica, 2019, 49(3): 284-301. doi: 10.1080/00498254.2018.1444814

    [4]

    Zhuang Y, Sun QS, Jing T, et al. Contributions of intestine and liver to the absorption and disposition of FZJ-003, a selective JAK1 inhibitor with structure modification of filgotinib[J]. Eur J Pharm Sci, 2022, 175: 106211. doi: 10.1016/j.ejps.2022.106211

    [5]

    Namour F, Anderson K, Nelson C, et al. Filgotinib: a clinical pharmacology review[J]. Clin Pharmacokinet, 2022, 61(6): 819-832. doi: 10.1007/s40262-022-01129-y

    [6]

    Meng A, Anderson K, Nelson C, et al. Exposure-response relationships for the efficacy and safety of filgotinib and its metabolite GS-829845 in subjects with rheumatoid arthritis based on phase 2 and phase 3 studies[J]. Br J Clin Pharmacol, 2022, 88(7): 3211-3221. doi: 10.1111/bcp.15239

    [7]

    Tilg H, Adolph TE, Trauner M. Gut-liver axis: Pathophysiological concepts and clinical implications[J]. Cell Metab, 2022, 34(11): 1700-1718. doi: 10.1016/j.cmet.2022.09.017

    [8]

    Basit A, Neradugomma NK, Wolford C, et al. Characterization of differential tissue abundance of major non-CYP enzymes in human[J]. Mol Pharm, 2020, 17(11): 4114-4124. doi: 10.1021/acs.molpharmaceut.0c00559

    [9]

    Song YR, Li CX, Liu GZ, et al. Drug-metabolizing cytochrome P450 enzymes have multifarious influences on treatment outcomes[J]. Clin Pharmacokinet, 2021, 60(5): 585-601. doi: 10.1007/s40262-021-01001-5

    [10]

    Fukami T, Yokoi T. The emerging role of human esterases[J]. Drug Metab Pharmacokinet, 2012, 27(5): 466-477. doi: 10.2133/dmpk.DMPK-12-RV-042

    [11]

    Fan PW, Zhang DL, Halladay JS, et al. Going beyond common drug metabolizing enzymes: case studies of biotransformation involving aldehyde oxidase, γ-glutamyl transpeptidase, cathepsin B, flavin-containing monooxygenase, and ADP-ribosyltransferase[J]. Drug Metab Dispos, 2016, 44(8): 1253-1261. doi: 10.1124/dmd.116.070169

    [12]

    Sodhi JK, Wong S, Kirkpatrick DS, et al. A novel reaction mediated by human aldehyde oxidase: amide hydrolysis of GDC-0834[J]. Drug Metab Dispos, 2015, 43(6): 908-915. doi: 10.1124/dmd.114.061804

    [13]

    Capasso R, Matias I, Lutz B, et al. Fatty acid amide hydrolase controls mouse intestinal motility in vivo[J]. Gastroenterology, 2005, 129(3): 941-951. doi: 10.1053/j.gastro.2005.06.018

    [14]

    Zhuang Y, Wang YX, Li N, et al. Hydrolytic metabolism of withangulatin A mediated by serum albumin instead of common esterases in plasma[J]. Eur J Drug Metab Pharmacokinet, 2023, 48(4): 363-376. doi: 10.1007/s13318-023-00834-8

    [15]

    Shimizu M, Fukami T, Nakajima M, et al. Screening of specific inhibitors for human carboxylesterases or arylacetamide deacetylase[J]. Drug Metab Dispos, 2014, 42(7): 1103-1109. doi: 10.1124/dmd.114.056994

    [16]

    Sato Y, Miyashita A, Iwatsubo T, et al. Simultaneous absolute protein quantification of carboxylesterases 1 and 2 in human liver tissue fractions using liquid chromatography-tandem mass spectrometry[J]. Drug Metab Dispos, 2012, 40(7): 1389-1396. doi: 10.1124/dmd.112.045054

    [17]

    Imai T. Human carboxylesterase isozymes: catalytic properties and rational drug design[J]. Drug Metab Pharmacokinet, 2006, 21(3): 173-185. doi: 10.2133/dmpk.21.173

    [18]

    Xu J, Qiu JC, Ji X, et al. Potential pharmacokinetic herb-drug interactions: have we overlooked the importance of human carboxylesterases 1 and 2?[J]. Curr Drug Metab, 2019, 20(2): 130-137. doi: 10.2174/1389200219666180330124050

    [19]

    Yan MC, Zhang Z, Liu ZM, et al. Catalytic hydrolysis mechanism of cocaine by human carboxylesterase 1: an orthoester intermediate slows down the reaction[J]. Molecules, 2019, 24(22): 4057. doi: 10.3390/molecules24224057

    [20]

    Wang YQ, Shang XF, Wang L, et al. Interspecies variation of clopidogrel hydrolysis in liver microsomes from various mammals[J]. Chem Biol Interact, 2020, 315: 108871. doi: 10.1016/j.cbi.2019.108871

    [21]

    Kisui F, Fukami T, Nakano M, et al. Strain and sex differences in drug hydrolase activities in rodent livers[J]. Eur J Pharm Sci, 2020, 142: 105143. doi: 10.1016/j.ejps.2019.105143

    [22]

    Di L. The impact of carboxylesterases in drug metabolism and pharmacokinetics[J]. Curr Drug Metab, 2019, 20(2): 91-102. doi: 10.2174/1389200219666180821094502

    [23]

    Sitbon O, Channick R, Chin KM, et al. Selexipag for the treatment of pulmonary arterial hypertension[J]. N Engl J Med, 2015, 373(26): 2522-2533. doi: 10.1056/NEJMoa1503184

    [24]

    Klose H, Chin KM, Ewert R, et al. Temporarily switching from oral to intravenous selexipag in patients with pulmonary arterial hypertension: safety, tolerability, and pharmacokinetic results from an open-label, phase III study[J]. Respir Res, 2021, 22(1): 34. doi: 10.1186/s12931-020-01594-8

    [25]

    Ichikawa T, Yamada T, Treiber A, et al. Pharmacokinetics of the selective prostacyclin receptor agonist selexipag in rats, dogs and monkeys[J]. Xenobiotica, 2018, 48(2): 186-196. doi: 10.1080/00498254.2017.1294277

    [26]

    Wagner C, Hois V, Taschler U, et al. KIAA1363-a multifunctional enzyme in xenobiotic detoxification and lipid ester hydrolysis[J]. Metabolites, 2022, 12(6): 516. doi: 10.3390/metabo12060516

    [27]

    Honda S, Fukami T, Tsujiguchi T, et al. Hydrolase activities of Cynomolgus monkey liver microsomes and recombinant CES1, CES2, and AADAC[J]. Eur J Pharm Sci, 2021, 161: 105807. doi: 10.1016/j.ejps.2021.105807

    [28]

    Kobayashi Y, Fukami T, Shimizu M, et al. Contributions of arylacetamide deacetylase and carboxylesterase 2 to flutamide hydrolysis in human liver[J]. Drug Metab Dispos, 2012, 40(6): 1080-1084. doi: 10.1124/dmd.112.044537

    [29]

    Hammid A, Fallon JK, Lassila T, et al. Activity and expression of carboxylesterases and arylacetamide deacetylase in human ocular tissues[J]. Drug Metab Dispos, 2022, 50(12): 1483-1492. doi: 10.1124/dmd.122.000993

    [30]

    Watanabe A, Fukami T, Takahashi S, et al. Arylacetamide deacetylase is a determinant enzyme for the difference in hydrolase activities of phenacetin and acetaminophen[J]. Drug Metab Dispos, 2010, 38(9): 1532-1537. doi: 10.1124/dmd.110.033720

    [31]

    Honda S, Fukami T, Hirosawa K, et al. Differences in hydrolase activities in the liver and small intestine between marmosets and humans[J]. Drug Metab Dispos, 2021, 49(9): 718-728. doi: 10.1124/dmd.121.000513

    [32]

    Sun RQ, Lin ZF, Wang XY, et al. Correction: AADAC protects colorectal cancer liver colonization from ferroptosis through SLC7A11-dependent inhibition of lipid peroxidation[J]. J Exp Clin Cancer Res, 2022, 41(1): 313. doi: 10.1186/s13046-022-02508-w

    [33]

    Kobayashi Y, Fukami T, Nakajima A, et al. Species differences in tissue distribution and enzyme activities of arylacetamide deacetylase in human, rat, and mouse[J]. Drug Metab Dispos, 2012, 40(4): 671-679. doi: 10.1124/dmd.111.043067

    [34]

    Kurokawa T, Fukami T, Yoshida T, et al. Arylacetamide deacetylase is responsible for activation of prasugrel in human and dog[J]. Drug Metab Dispos, 2016, 44(3): 409-416. doi: 10.1124/dmd.115.068221

    [35]

    Mahomoodally F, Abdallah HH, Suroowan S, et al. In silico exploration of bioactive phytochemicals against neurodegenerative diseases via inhibition of cholinesterases[J]. Curr Pharm Des, 2020, 26 (33): 4151-4162.

    [36]

    Silman I. The multiple biological roles of the cholinesterases[J]. Prog Biophys Mol Biol, 2021, 162: 41-56. doi: 10.1016/j.pbiomolbio.2020.12.001

    [37]

    Gok M, Cicek C, Sari S, et al. Novel activity of human BChE: lipid hydrolysis[J]. Biochimie, 2023, 204: 127-135. doi: 10.1016/j.biochi.2022.09.008

    [38]

    Bodur E, Cokuğraş AN, Tezcan EF. Inhibition effects of benactyzine and drofenine on human serum butyrylcholinesterase[J]. Arch Biochem Biophys, 2001, 386(1): 25-29. doi: 10.1006/abbi.2000.2188

    [39]

    Atay MS, Sari S, Bodur E. Molecular and computational analysis identify statins as selective inhibitors of human butyrylcholinesterase[J]. Protein J, 2023, 42(2): 104-111. doi: 10.1007/s10930-023-10090-z

    [40]

    Cao MD, Luo XY, Wu KM, et al. Targeting lysosomes in human disease: from basic research to clinical applications[J]. Signal Transduct Target Ther, 2021, 6(1): 379. doi: 10.1038/s41392-021-00778-y

    [41]

    Stoka V, Vasiljeva O, Nakanishi H, et al. The role of cysteine protease cathepsins B, H, C, and X/Z in neurodegenerative diseases and cancer[J]. Int J Mol Sci, 2023, 24(21): 15613. doi: 10.3390/ijms242115613

    [42]

    Mohamed MM, Sloane BF. Cysteine cathepsins: multifunctional enzymes in cancer[J]. Nat Rev Cancer, 2006, 6(10): 764-775. doi: 10.1038/nrc1949

    [43]

    Li DP, Sun XY, Li YQ, et al. AGCM-22, a novel cetuximab-based EGFR-targeting antibody-drug-conjugate with highly selective anti-glioblastoma efficacy[J]. Bioorg Med Chem, 2024, 102: 117657. doi: 10.1016/j.bmc.2024.117657

    [44]

    Satsangi A, Roy SS, Satsangi RK, et al. Design of a paclitaxel prodrug conjugate for active targeting of an enzyme upregulated in breast cancer cells[J]. Mol Pharm, 2014, 11(6): 1906-1918. doi: 10.1021/mp500128k

    [45]

    Kozminski KD, Selimkhanov J, Heyward S, et al. Contribution of extrahepatic aldehyde oxidase activity to human clearance[J]. Drug Metab Dispos, 2021, 49(9): 743-749. doi: 10.1124/dmd.120.000313

    [46]

    Busby RW, Cai XK, Yang S, et al. Metopimazine is primarily metabolized by a liver amidase in humans[J]. Pharmacol Res Perspect, 2022, 10(1): e00903. doi: 10.1002/prp2.903

    [47]

    Schofield PC, Robertson IG, Paxton JW. Inter-species variation in the metabolism and inhibition of N-[(2'-dimethylamino)ethyl] acridine-4-carboxamide (DACA) by aldehyde oxidase[J]. Biochem Pharmacol, 2000, 59(2): 161-165. doi: 10.1016/S0006-2952(99)00323-8

    [48]

    Pertwee RG. Elevating endocannabinoid levels: pharmacological strategies and potential therapeutic applications[J]. Proc Nutr Soc, 2014, 73(1): 96-105. doi: 10.1017/S0029665113003649

    [49]

    van Egmond N, Straub VM, van der Stelt M. Targeting endocannabinoid signaling: FAAH and MAG lipase inhibitors[J]. Annu Rev Pharmacol Toxicol, 2021, 61: 441-463. doi: 10.1146/annurev-pharmtox-030220-112741

    [50]

    Rabbani G, Ahn SN. Structure, enzymatic activities, glycation and therapeutic potential of human serum albumin: a natural cargo[J]. Int J Biol Macromol, 2019, 123: 979-990. doi: 10.1016/j.ijbiomac.2018.11.053

    [51]

    De Simone G, di Masi A, Ascenzi P. Serum albumin: a multifaced enzyme[J]. Int J Mol Sci, 2021, 22(18): 10086. doi: 10.3390/ijms221810086

    [52]

    Kono K, Fukuchi Y, Okawa H, et al. Unique hydrolysis of an ester-type prodrug of levodopa in human plasma: relay-type role sharing between alpha-1 acid glycoprotein and human serum albumin[J]. Mol Pharm, 2019, 16(10): 4131-4138. doi: 10.1021/acs.molpharmaceut.9b00435

    [53]

    Watanabe H, Tanase S, Nakajou K, et al. Role of arg-410 and Tyr-411 in human serum albumin for ligand binding and esterase-like activity[J]. Biochem J, 2000, 349 (Pt 3): 813-819.

    [54]

    Sun L, Mi K, Hou YX, et al. Pharmacokinetic and pharmacodynamic drug-drug interactions: research methods and applications[J]. Metabolites, 2023, 13(8): 897. doi: 10.3390/metabo13080897

    [55]

    Tsugoshi Y, Watanabe Y, Tanikawa Y, et al. Inhibitory effects of organophosphate esters on carboxylesterase activity of rat liver microsomes[J]. Chem Biol Interact, 2020, 327: 109148. doi: 10.1016/j.cbi.2020.109148

    [56]

    Khidkhan K, Poapolathep S, Kulprasertsri S, et al. Comparative in vitro biotransformation of fipronil in domestic poultry using liver microsome[J]. J Vet Sci, 2022, 23(6): e82. doi: 10.4142/jvs.22178

    [57]

    Wang XW, He B, Shi J, et al. Comparative proteomics analysis of human liver microsomes and S9 fractions[J]. Drug Metab Dispos, 2020, 48(1): 31-40. doi: 10.1124/dmd.119.089235

    [58]

    Qiao SD, Feng SS, Wu ZT, et al. Functional proliferating human hepatocytes: in vitro hepatocyte model for drug metabolism, excretion, and toxicity[J]. Drug Metab Dispos, 2021, 49(4): 305-313. doi: 10.1124/dmd.120.000275

    [59]

    Wang HB, Brown PC, Chow ECY, et al. 3D cell culture models: drug pharmacokinetics, safety assessment, and regulatory consideration[J]. Clin Transl Sci, 2021, 14(5): 1659-1680. doi: 10.1111/cts.13066

    [60]

    Marsee A, Roos FJM, Verstegen MMA, et al. Building consensus on definition and nomenclature of hepatic, pancreatic, and biliary organoids[J]. Cell Stem Cell, 2021, 28(5): 816-832. doi: 10.1016/j.stem.2021.04.005

    [61]

    Heydari Z, Moeinvaziri F, Agarwal T, et al. Organoids: a novel modality in disease modeling[J]. Biodes Manuf, 2021, 4(4): 689-716. doi: 10.1007/s42242-021-00150-7

    [62]

    Miller CO, Cao J. Probing hepatic glucose metabolism via 13C NMR spectroscopy in perfused livers-applications to drug development[J]. Metabolites, 2021, 11(11): 712. doi: 10.3390/metabo11110712

    [63]

    Blondeel J, Gilbo N, Wylin T, et al. Porcine normothermic isolated liver perfusion[J]. J Vis Exp, 2023(196): (196).

    [64]

    Czuba LC, Wu X, Huang WZ, et al. Altered vitamin A metabolism in human liver slices corresponds to fibrogenesis[J]. Clin Transl Sci, 2021, 14(3): 976-989. doi: 10.1111/cts.12962

    [65]

    Davies M, Peramuhendige P, King L, et al. Evaluation of in vitro models for assessment of human intestinal metabolism in drug discovery[J]. Drug Metab Dispos, 2020, 48(11): 1169-1182. doi: 10.1124/dmd.120.000111

    [66]

    Chen X, Yu FJ, Guo XL, et al. Clock gene Bmal1 controls diurnal rhythms in expression and activity of intestinal carboxylesterase 1[J]. J Pharm Pharmacol, 2021, 73(1): 52-59. doi: 10.1093/jpp/rgaa035

    [67]

    Li AP. In vitro human cell-based experimental models for the evaluation of enteric metabolism and drug interaction potential of drugs and natural products[J]. Drug Metab Dispos, 2020, 48(10): 980-992. doi: 10.1124/dmd.120.000053

    [68]

    Li AP, Alam N, Amaral K, et al. Cryopreserved human intestinal mucosal epithelium: a novel in vitro experimental system for the evaluation of enteric drug metabolism, cytochrome P450 induction, and enterotoxicity[J]. Drug Metab Dispos, 2018, 46(11): 1562-1571. doi: 10.1124/dmd.118.082875

    [69]

    Tian CM, Yang MF, Xu HM, et al. Stem cell-derived intestinal organoids: a novel modality for IBD[J]. Cell Death Discov, 2023, 9(1): 255. doi: 10.1038/s41420-023-01556-1

    [70]

    Cavallero A, Puccini P, Aprile V, et al. Presence, enzymatic activity, and subcellular localization of paraoxonases 1, 2, and 3 in human lung tissues[J]. Life Sci, 2022, 311 (Pt A): 121147.

    [71]

    Liu SB, Wang ZT, Tian X, et al. Predicting the effects of CYP2C19 and carboxylesterases on vicagrel, a novel P2Y12 antagonist, by physiologically based pharmacokinetic/pharmacodynamic modeling approach[J]. Front Pharmacol, 2020, 11: 591854. doi: 10.3389/fphar.2020.591854

    [72]

    Parker RB, Casey Laizure S. The effect of ethanol on oral cocaine pharmacokinetics reveals an unrecognized class of ethanol-mediated drug interactions[J]. Drug Metab Dispos, 2010, 38(2): 317-322. doi: 10.1124/dmd.109.030056

    [73]

    Zhu T, Wu Y, Li XM, et al. Vicagrel is hydrolyzed by Raf kinase inhibitor protein in human intestine[J]. Biopharm Drug Dispos, 2022, 43(6): 247-254. doi: 10.1002/bdd.2340

    [74]

    Xu AN, He F, Zhang XN, et al. Tacrine-hydroxamate derivatives as multitarget-directed ligands for the treatment of Alzheimer’s disease: design, synthesis, and biological evaluation[J]. Bioorg Chem, 2020, 98: 103721. doi: 10.1016/j.bioorg.2020.103721

    [75]

    Mijanović O, Branković A, Panin AN, et al. Cathepsin B: a sellsword of cancer progression[J]. Cancer Lett, 2019, 449: 207-214. doi: 10.1016/j.canlet.2019.02.035

表(2)
计量
  • 文章访问数:  77
  • HTML全文浏览量:  26
  • PDF下载量:  17
  • 被引次数: 0
出版历程
  • 收稿日期:  2024-10-11
  • 刊出日期:  2025-04-24

目录

    /

    返回文章
    返回
    x 关闭 永久关闭