Stereoselectivity of chiral drug transport: a focus on enantiomer-transporter interaction.

Abstract:

:Drug transporters and drug metabolism enzymes govern drug absorption, distribution, metabolism and elimination. Many literature works presenting important aspects related to stereochemistry of drug metabolism are available. However, there is very little literature on stereoselectivity of chiral drug transport and enantiomer-transporter interaction. In recent years, the experimental research within this field showed good momentum. Herein, an up-to-date review on this topic was presented. Breast Cancer Resistance Protein (BCRP), Multidrug Resistance Proteins (MRP), P-glycoprotein (P-gp), Organic Anion Transporters (OATs), Organic Anion Transporting Polypeptides (OATPs), Organic Cation Transporters (OCTs), Peptide Transport Proteins (PepTs), Human Proton-Coupled Folate Transporter (PCFT) and Multidrug and Toxic Extrusion Proteins (MATEs), have been reported to exhibit either positive or negative enantio-selective substrate recognition. The approaches utilized to study chirality in enantiomer-transporter interaction include inhibition experiments of specific transporters in cell models (e.g. Caco-2 cells), transport study using drug resistance cell lines or transgenic cell lines expressing transporters in wild type or variant, the use of transporter knockout mice, pharmacokinetics association of single nucleotide polymorphism in transporters, pharmacokinetic interaction study of racemate in the presence of specific transporter inhibitor or inducer, molecule cellular membrane affinity chromatography and pharmacophore modeling. Enantiomer-enantiomer interactions exist in chiral transport. The strength and/or enantiomeric preference of stereoselectivity may be species or tissue-specific, concentration-dependent and transporter family member-dependent. Modulation of specific drug transporter by pure enantiomers might exhibit opposite stereoselectivity. Further studies with integrated approaches will open up new horizons in stereochemistry of pharmacokinetics.

journal_name

Drug Metab Rev

journal_title

Drug metabolism reviews

authors

Zhou Q,Yu LS,Zeng S

doi

10.3109/03602532.2014.887094

subject

Has Abstract

pub_date

2014-08-01 00:00:00

pages

283-90

issue

3

eissn

0360-2532

issn

1097-9883

journal_volume

46

pub_type

杂志文章,评审
  • NAT1 genotypic and phenotypic contribution to urinary bladder cancer risk: a systematic review and meta-analysis.

    abstract::N-acetyltransferase 1 (NAT1), a polymorphic Phase II enzyme, plays an essential role in metabolizing heterocyclic and aromatic amines, which are implicated in urinary bladder cancer (BCa). This systematic review investigates a possible association between the different NAT1 genetic polymorphisms and BCa risk. Medline,...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,meta分析,评审

    doi:10.1080/03602532.2017.1415928

    authors: Dhaini HR,El Hafi B,Khamis AM

    更新日期:2018-05-01 00:00:00

  • Predictive models for human glucose-6-phosphate dehydrogenase deficiency.

    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

    authors: Horton HM,Calabrese EJ

    更新日期:1986-01-01 00:00:00

  • The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modeling.

    abstract::Glycyrrhizic acid is widely applied as a sweetener in food products and chewing tobacco. In addition, it is of clinical interest for possible treatment of chronic hepatitis C. In some highly exposed subjects, side effects such as hypertension and symptoms associated with electrolyte disturbances have been reported. To...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1081/dmr-100104400

    authors: Ploeger B,Mensinga T,Sips A,Seinen W,Meulenbelt J,DeJongh J

    更新日期:2001-05-01 00:00:00

  • Structure, function, regulation and polymorphism and the clinical significance of human cytochrome P450 1A2.

    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

    authors: Zhou SF,Wang B,Yang LP,Liu JP

    更新日期:2010-05-01 00:00:00

  • Cytochrome P450-based cancer gene therapy: recent advances and future prospects.

    abstract::Cytochrome P450-based cancer gene therapy is a novel prodrug activation strategy for cancer treatment that has substantial potential for improving the safety and efficacy of cancer chemotherapeutics. The primary goal of this strategy is to selectively increase tumor cell exposure to cytotoxic drug metabolites generate...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1081/dmr-100101933

    authors: Waxman DJ,Chen L,Hecht JE,Jounaidi Y

    更新日期:1999-05-01 00:00:00

  • Effects of induction of cytochrome P-450 enzymes on the concentration of foreign compounds and their metabolites and on the toxicological effects of these compounds.

    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

    authors: Gillette JR

    更新日期:1979-01-01 00:00:00

  • Structure and regulation of P-450s in the rat P450IIA gene subfamily.

    abstract::The rat P450IIA subfamily was characterized at the protein, cDNA, and gene level. The purified IIA1 and IIA2 P-450s displayed distinct positional specificities toward hydroxylation of the prototype substrate testosterone. The IIA1 and IIA2 genes were also regulated differently during development; IIA1 was expressed wi...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章

    doi:10.3109/03602538909103582

    authors: Gonzalez FJ,Matsunaga T,Nagata K

    更新日期:1989-01-01 00:00:00

  • Nuclear receptors and endobiotics glucuronidation: the good, the bad, and the UGT.

    abstract::The recent progresses in molecular biology and pharmacology approaches allowed the characterization of a series of nuclear receptors (NRs) as efficient regulators of uridine diphosphate glucuronosyltransferase (UGT) genes activity. These regulatory processes ensure an optimized UGT expression in response to specific e...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.3109/03602532.2012.751992

    authors: Bigo C,Caron S,Dallaire-Théroux A,Barbier O

    更新日期:2013-02-01 00:00:00

  • Mechanisms regulating human FMO3 transcription.

    abstract::Flavin-containing monooxygenases (FMOs) are important oxidative drug metabolizing enzymes. FMO3 is the primary human adult liver FMO enzyme, but is developmentally regulated. FMO3 promoter characterization using in vitro DNA binding assays with HepG2 cell and fetal and adult liver nuclear protein, as well as FMO3/repo...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章

    doi:10.1080/03602530701498612

    authors: Klick DE,Hines RN

    更新日期:2007-01-01 00:00:00

  • Practical aspects of transporter model systems: a case study involving SQV.

    abstract::In this case study, in vitro and in vivo data were provided for saquinavir (SQV) showing that drug transporters play a significant role in the absorption and disposition of drugs. This article is focused on the more practical points with a technical emphasis. Currently many in vitro and in vivo experimental models hav...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1081/dmr-120037570

    authors: Su Y,Lee SH,Sinko PJ

    更新日期:2004-05-01 00:00:00

  • Substrate selectivity of drug-metabolizing cytochrome P450s predicted from crystal structures and in silico modeling.

    abstract::Enormous efforts toward predicting the metabolic fate of a drug have been driven by the high attrition rate in drug development. To accelerate such efforts, it is critical to elucidate the molecular mechanisms of drug recognition by drug-metabolizing enzymes. Therefore, it is not surprising that an increasing number o...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.3109/03602532.2011.645581

    authors: Dong D,Wu B

    更新日期:2012-02-01 00:00:00

  • Gold nanostars-diagnosis, bioimaging and biomedical applications.

    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

    authors: Mousavi SM,Zarei M,Hashemi SA,Ramakrishna S,Chiang WH,Lai CW,Gholami A

    更新日期:2020-05-01 00:00:00

  • Entering the era of computationally driven drug development.

    abstract::Historically, failure rates in drug development are high; increased sophistication and investment throughout the process has shifted the reasons for attrition, but the overall success rates have remained stubbornly and consistently low. Only 8% of new entities entering clinical testing gain regulatory approval, indica...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1080/03602532.2020.1726944

    authors: Maharao N,Antontsev V,Wright M,Varshney J

    更新日期:2020-05-01 00:00:00

  • Quantitative relationships between dynamics and kinetics of drugs: a systems dynamics approach.

    abstract::The body is considered as a system composed of a number of subsystems. The response(s) of a drug is a complicated function of the concentration in the blood plasma, which in turn is some function of the dosage input. The dose-response curve of a drug in a subsystem (e.g., isolated organ) is, over a limited concentrati...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.3109/03602538409015072

    authors: van Rossum JM,Burgers JP

    更新日期:1984-01-01 00:00:00

  • Pharmacokinetic herb-drug interactions with traditional Chinese medicine: progress, causes of conflicting results and suggestions for future research.

    abstract::Traditional Chinese medicine (TCM) has a long history of medical use in China and is still used worldwide. Unexpected herb-drug interactions (HDIs) may lead to adverse drug reactions or loss of therapeutic efficacy of the victim drug. Here, based on searches of Medline, EBSCO, Science Direct and Web of Science using v...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.3109/03602532.2015.1124888

    authors: Ma BL,Ma YM

    更新日期:2016-01-01 00:00:00

  • Pharmacogenetic screening of the gene deletion and duplications of CYP2D6.

    abstract::Cytochrome P450 (CYP) 2D6 is one of the most important enzymes involved in the metabolism of drugs. Multiple, clinically relevant, genetic variants of this gene have been identified and, among them, a gene deletion as well as multiplications of the gene. These large structural mutations in CYP2D6 occur at a relatively...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1080/03602530600952206

    authors: Meijerman I,Sanderson LM,Smits PH,Beijnen JH,Schellens JH

    更新日期:2007-01-01 00:00:00

  • Metabolism of bioconjugate therapeutics: why, when, and how?

    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...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1080/03602532.2020.1716784

    authors: Liu H,Bolleddula J,Nichols A,Tang L,Zhao Z,Prakash C

    更新日期:2020-02-01 00:00:00

  • Drug transporters: gatekeepers controlling access of xenobiotics to the cellular interior.

    abstract::In this paper, we evaluate methodologies and null mouse models used to study drug transporter function in vitro and in vivo. P-glycoprotein and MRP null mice have been used to examine many aspects of xenobiotic distribution and bioavailability. Their advantage over conventional models is that they allow the exclusion ...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1080/03602530802605040

    authors: Stanley LA,Horsburgh BC,Ross J,Scheer N,Wolf CR

    更新日期:2009-01-01 00:00:00

  • LC-MS-based metabolomics in drug metabolism.

    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

    authors: Chen C,Gonzalez FJ,Idle JR

    更新日期:2007-01-01 00:00:00

  • The fourth mammalian molybdenum enzyme mARC: current state of research.

    abstract::The mitochondrial amidoxime-reducing component (mARC) is a recently discovered molybdenum-containing enzyme in mammalians. Upon reconstitution with the electron transport proteins, cytochrome b(5) and its reductase, this molybdenum enzyme is capable of reducing N-hydroxylated compounds. It was named mARC because the N...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.3109/03602532.2011.608682

    authors: Havemeyer A,Lang J,Clement B

    更新日期:2011-11-01 00:00:00

  • Sulfotransferase genes: regulation by nuclear receptors in response to xeno/endo-biotics.

    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

    authors: Kodama S,Negishi M

    更新日期:2013-11-01 00:00:00

  • Early drug safety evaluation: biomarkers, signatures, and fingerprints.

    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

    authors: Roberts R,Cain K,Coyle B,Freathy C,Leonard JF,Gautier JC

    更新日期:2003-11-01 00:00:00

  • Adverse pharmacokinetic interactions between illicit substances and clinical drugs.

    abstract::Adverse pharmacokinetic interactions between illicit substances and clinical drugs are of a significant health concern. Illicit substances are taken by healthy individuals as well as by patients with medical conditions such as mental illnesses, acquired immunodeficiency syndrome, diabetes mellitus and cancer. Many ind...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1080/03602532.2019.1697283

    authors: Abbott KL,Flannery PC,Gill KS,Boothe DM,Dhanasekaran M,Mani S,Pondugula SR

    更新日期:2020-02-01 00:00:00

  • Nano-hydroxyapatite use in dentistry: a systematic review.

    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

    pub_type: 杂志文章

    doi:10.1080/03602532.2020.1758713

    authors: Bordea IR,Candrea S,Alexescu GT,Bran S,Băciuț M,Băciuț G,Lucaciu O,Dinu CM,Todea DA

    更新日期:2020-05-01 00:00:00

  • The role of aryl hydrocarbon receptor in the pathogenesis of cardiovascular diseases.

    abstract::Numerous experimental and epidemiological studies have demonstrated that polycyclic aromatic hydrocarbons (PAHs), which are major constituents of cigarette tobacco tar, are strongly involved in the pathogenesis of the cardiovascular diseases (CVDs). Knowing that PAH-induced toxicities are mediated by the activation of...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1080/03602530600632063

    authors: Korashy HM,El-Kadi AO

    更新日期:2006-01-01 00:00:00

  • Mechanism and role of covalent heme binding in the CYP4 family of P450 enzymes and the mammalian peroxidases.

    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

    authors: Ortiz de Montellano PR

    更新日期:2008-01-01 00:00:00

  • Synthetic cannabinoids pharmacokinetics and detection methods in biological matrices.

    abstract::Synthetic cannabinoids (SC), originally developed as research tools, are now highly abused novel psychoactive substances. We present a comprehensive systematic review covering in vivo and in vitro animal and human pharmacokinetics and analytical methods for identifying SC and their metabolites in biological matrices. ...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.3109/03602532.2015.1029635

    authors: Castaneto MS,Wohlfarth A,Desrosiers NA,Hartman RL,Gorelick DA,Huestis MA

    更新日期:2015-05-01 00:00:00

  • A review of public policy issues in promoting the development and commercialization of pharmacogenomic applications: challenges and implications.

    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

    authors: Garrison LP Jr,Carlson RJ,Carlson JJ,Kuszler PC,Meckley LM,Veenstra DL

    更新日期:2008-01-01 00:00:00

  • The right compound in the right assay at the right time: an integrated discovery DMPK strategy.

    abstract::The high rate of attrition during drug development and its associated high research and development (R&D) cost have put pressure on pharmaceutical companies to ensure that candidate drugs going to clinical testing have the appropriate quality such that the biological hypothesis could be evaluated. To help achieve this...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.3109/03602532.2012.691099

    authors: Ballard P,Brassil P,Bui KH,Dolgos H,Petersson C,Tunek A,Webborn PJ

    更新日期:2012-08-01 00:00:00

  • Novel insights into the complex pharmacokinetics of voriconazole: a review of its metabolism.

    abstract::Voriconazole, a second-generation triazole frequently used for the prophylaxis and treatment of invasive fungal infections, undergoes complex metabolism mainly involving various (polymorphic) cytochrome P450 enzymes in humans. Although high inter- and intraindividual variability in voriconazole pharmacokinetics have b...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1080/03602532.2019.1632888

    authors: Schulz J,Kluwe F,Mikus G,Michelet R,Kloft C

    更新日期:2019-08-01 00:00:00