Abstract:
:Bioconjugation of therapeutic agents has been used as a selective drug delivery platform for many therapeutic areas. Bioconjugates are prepared by the covalent linkage of active compounds (small or large molecule) to a carrier molecule (lipids, proteins, peptides, carbohydrates, and polymers) through a chemical linker. The linkage of the active component to a carrier molecule enhances the therapeutic window through a targeted delivery and by reducing toxicity. Bioconjugates also possess improved pharmacokinetic properties such as a long half-life, increased stability, and cleavage by intracellular enzymes/environment. However, premature cleavage of the bioconjugates and the resulting metabolites/catabolites may produce undesirable toxic effects and, hence, it is critical to understand cleavage mechanisms, metabolism of bioconjugates, and translatability to human in the discovery stages. This article provides a comprehensive overview of linker cleavage pathways and catabolism/metabolism of antibody-drug conjugates, glycoconjugates, polymer-drug conjugates, lipid-drug conjugates, folate-targeted small molecule-drug conjugates, and drug-drug conjugates.
journal_name
Drug Metab Revjournal_title
Drug metabolism reviewsauthors
Liu H,Bolleddula J,Nichols A,Tang L,Zhao Z,Prakash Cdoi
10.1080/03602532.2020.1716784subject
Has Abstractpub_date
2020-02-01 00:00:00pages
66-124issue
1eissn
0360-2532issn
1097-9883journal_volume
52pub_type
杂志文章,评审abstract::The multiple functions of NAD(P)H:quinone oxidoreductase 1 (NQO1, DT-diaphorase) in the cell are reviewed. NQO1 has long been viewed as a chemoprotective enzyme involved in cellular defense against the electrophilic and oxidizing metabolites of xenobiotic quinones. It also participates in reduction of endogenous quino...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1081/dmr-200033465
更新日期:2004-10-01 00:00:00
abstract::The present paper has discussed available test systems for determination of the response of G-6-PD-deficient human erythrocytes to environmental agents. The limitations and advantages of each model have been examined, and the results of research using each model have been presented. The future development of suitable ...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602538608998292
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abstract::1. The metabolic activity of the gastrointestinal microflora can be modified by numerous factors derived from the host, the host's environment, and the flora itself. 2. Marked differences exist in microbial composition and metabolism of the gut floras of different species of animal, and in the degree of colonization o...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602538808994135
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abstract::This article reviews the regulatory, social, policy, and other issues that will shape the development of pharmacogenomics applications. We identify and analyze 19 key public policy issues, ranging from the economic incentives for linked diagnostic-drug development, to the regulation of tests and drugs, and to privacy ...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602530801952500
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abstract::The physiological and biochemical measurements that can be performed noninvasively in humans with modern imaging techniques offer great promise for defining the precise state of a patient's disease and its response to therapy. In general, there are two critical points in drug development when PET measurements are like...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602539709002238
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abstract::Indirect evidence for the participation of cytochrome P450 (P450) in the microsomal N-oxygenation of primary and N-substituted amine functions is presented by studies employing diagnostic modifiers of the hemoprotein system as well as immunochemical approaches. Experiments with recombinant hemoproteins or isozymes pur...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1081/dmr-120005646
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abstract::The reabsorptive and excretory capacity of the kidney has an important influence on the systemic concentration of drugs. Multidrug resistance proteins (MRP/ABCC) expressed in the kidney play a critical role in the tubular efflux of a wide variety of drugs and toxicants, and, in particular, of their negatively charged ...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602530500205275
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abstract::Pregnane X receptor (PXR) and constitutive active/androstane receptor (CAR), members of the nuclear receptor superfamily, are two major xeno-sensing transcription factors. They can be activated by a broad range of lipophilic xenobiotics including therapeutics drugs. In addition to xenobiotics, endogenous compounds suc...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602532.2013.835630
更新日期:2013-11-01 00:00:00
abstract::The CYP4 family of cytochrome P450 enzymes and the mammalian peroxidases covalently bind their heme groups. In the CYP4 enzymes this involves one, and in the peroxidases two, covalent ester links between heme methys and carboxylic acid side-chains. In addition, in myeloperoxidase, a methionine forms a sulfonium link t...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602530802186439
更新日期:2008-01-01 00:00:00
abstract::Monkeys, especially macaques, including cynomolgus (Macaca fascicularis) and rhesus monkeys (Macaca mulatta), are frequently used in drug metabolism studies due to their evolutionary closeness to humans. Recently, numerous cytochrome P450 (P450 or CYP) cDNAs have been identified and characterized in cynomolgus and rhe...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602532.2010.549492
更新日期:2011-08-01 00:00:00
abstract::Most foreign compounds, including nonnutrients in foods and vapors in air, undergo extensive metabolism before they are eliminated from the body. Included in this paper are discussions of the urinary clearance of various kinds of foreign compounds, the nonspecific enzymes that catalyze the formation of many metabolite...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602537908993901
更新日期:1979-01-01 00:00:00
abstract::Xenobiotic metabolism, a ubiquitous natural response to foreign compounds, elicits initiating signals for many pathophysiological events. Currently, most widely used techniques for identifying xenobiotic metabolites and metabolic pathways are empirical and largely based on in vitro incubation assays and in vivo radiot...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602530701497804
更新日期:2007-01-01 00:00:00
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journal_title:Drug metabolism reviews
pub_type: 杂志文章
doi:10.1080/03602530701498612
更新日期:2007-01-01 00:00:00
abstract::When target organ toxicity arises in animal models during routine drug safety evaluation, it raises several key questions: Is this target organ toxicity related to the pharmacology? What is the mode of action (MOA)? Is the target organ toxicity relevant to humans? Pathology or prior knowledge of the compound class may...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1081/dmr-120026395
更新日期:2003-11-01 00:00:00
abstract::At present, the methods and enzymology of the UDP-glucuronosyltransferases (UGTs) lag behind that of the cytochromes P450 (CYPs). About 15 human UGTs have been identified, and knowledge about their regulation, substrate selectivity, and tissue distribution has progressed recently. Alamethicin has been characterized as...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1081/dmr-120000653
更新日期:2001-08-01 00:00:00
abstract::Gold Nanostars (GNS) have attracted tremendous attention toward themselves owing to their multi-branched structure and unique properties. These state of the art metallic nanoparticles possess intrinsic features like remarkable optical properties and exceptional physiochemical activities. These star-shaped gold nanopar...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602532.2020.1734021
更新日期:2020-05-01 00:00:00
abstract::Mineral fibers, including asbestos, are ubiquitous contaminants of the environment. Asbestos fibers are generally present at levels below 1 fiber/L in air though 10 fibers/L may be found in cities; these levels do not appear to be high enough to present a hazard to health. These fibers come mostly from the use of fibr...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602539408998321
更新日期:1994-01-01 00:00:00
abstract::The cytochrome P450 (P450) field came out of interest in the metabolism of drugs, carcinogens, and steroids, which remain major focal points. Over the years we have come to understand the P450 system components, the multiplicity of P450s, and many aspects of the regulation of the genes and also the catalytic mechanism...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1081/dmr-120033996
更新日期:2004-05-01 00:00:00
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journal_title:Drug metabolism reviews
pub_type: 杂志文章,meta分析,评审
doi:10.1080/03602532.2017.1415928
更新日期:2018-05-01 00:00:00
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journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602532.2019.1632888
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journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602532.2014.982865
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journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602530701690374
更新日期:2007-01-01 00:00:00
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journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602532.2020.1726944
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journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602532.2018.1428342
更新日期:2018-02-01 00:00:00
abstract::Human CYP1A2 is one of the major CYPs in human liver and metabolizes a number of clinical drugs (e.g., clozapine, tacrine, tizanidine, and theophylline; n > 110), a number of procarcinogens (e.g., benzo[a]pyrene and aromatic amines), and several important endogenous compounds (e.g., steroids). CYP1A2 is subject to rev...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602530903286476
更新日期:2010-05-01 00:00:00
abstract::For patients undergoing cardiopulmonary bypass (CPB) during cardiac surgery, there are well-documented changes in the pharmacokinetics (PK) of commonly administered drugs. Although multiple factors potentially underpin these changes, there has been scant research attention on the impact of CPB to alter the activities ...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
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abstract::Nano-hydroxyapatite (nano-HA) is a material with multiple uses due to its biocompatibility and its resemblance to the nonorganic bone structure. It is used in various dental domains such as implantology, surgery, periodontology, esthetics and prevention. The aim of this study is to provide a wide understanding of nano...
journal_title:Drug metabolism reviews
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abstract::Global statistical data shed light on an alarming trend that every year thousands of people die due to adverse drug reactions as each individual responds in a different way to the same drug. Pharmacogenomics has come up as a promising field in drug development and clinical medication in the past few decades. It has em...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
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abstract::Chemicals that cause toxicity though a direct mechanism, such as acetaminophen, covalently bind to a select group of proteins prior to the development of toxicity, and these proteins may be important in the initiation of the events that lead to the hepatotoxicity. Disruption of the cell is measured by release of intra...
journal_title:Drug metabolism reviews
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