subject:(Cytochrome P450 3A4)

University of Utah

1. Moore, Chad Douglas. Dehydrogenation of Raloxifene by Cytochrome P450 3A4.

Degree: PhD, Pharmacology & Toxicology;, 2010, University of Utah

URL: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1401/rec/288

► Raloxifene was approved in 2007 by the FDA for the chemoprevention of breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high… (more)

▼ Raloxifene was approved in 2007 by the FDA for the chemoprevention of breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer. The FDA's decision was based, in part, on a more favorable safety profile for raloxifene, as compared to the standard treatment of tamoxifen. However, recent studies have demonstrated the ability of raloxifene to form reactive intermediates and to act as a mechanism-based inactivator of cytochrome P450 3A4 (CYP3A4). The reactive raloxifene intermediate was theorized to be produced either through CYP3A4-mediated dehydrogenation to a di-quinone methide or through the more common oxygenation route to an arene oxide. However, the operative mechanism was never identified. The goal of this dissertation was to characterize the reactive intermediate formation from raloxifene, specifically the ability of CYP3A4 to catalyze the dehydrogenation of raloxifene to a di-quinone methide, using a combination of convent•i onal b•i oc«h emi•c ali and-i computati• onal techn•i ques. In the current woir k,1 8O incorporation studies were utilized to differentiate CYP3A4-mediated oxygenation versus dehydrogenation of raloxifene. These studies established that 3'-hydroxyraloxifene is produced exclusively via CYP3A4-mediated oxygenation with molecular O2. These studies also provided convincing evidence for the mechanism of CYP3A4-mediated dehydrogenation of raloxifene to a reactive di-quinone methide, and excluded the alternative arene oxide pathway. Furthermore, it was demonstrated that 7-hydroxyraloxifene, which was previously believed to be a typical 02-derived metabolite of CYP3A4, is in fact produced by a highly unusual hydrolysis pathway from a putative ester, formed by conjugation of a carboxylic acid moiety of CYP3A4 or another protein, with the di-quinone methide of raloxifene. The use of molecular modeling in conjunction with site-directed mutagenesis has extensively been used to study substrate orientation within the P450 active sites, and to identify potential residues involved in positioning and/or catalysis of these substrates. However, the effectiveness of these studies is highly dependent on the selection of the most accurate enzyme crystal structure. In the current work, we compared the ability of two commonly used CYP3A4 crystal structures, 1TQN and 1 WOE, to predict the sites of metabolism of two known CYP3A4 substrates, indapamide and raloxifene. Indapamide was used to evaluate the accuracy of the molecular model, while raloxifene was used to investigate the effects of adding partial charges to the P450 heme moiety to improve predictions of metabolic pathways by computation methods. The results demonstrated that while docking studies with both 1TQN and 1 WOE crystal structures could accurately predict the sites of indapamide metabolism, the interactions between the substrate and active site residues were different for each crystal structure. The addition of partial charges to the heme moiety of 1 WOE dramatically increased the…

Subjects/Keywords: Raloxifene; Dehydrogenation; Cytochrome P450 3A4

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APA (6^th Edition):

Moore, C. D. (2010). Dehydrogenation of Raloxifene by Cytochrome P450 3A4. (Doctoral Dissertation). University of Utah. Retrieved from http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1401/rec/288

Chicago Manual of Style (16^th Edition):

Moore, Chad Douglas. “Dehydrogenation of Raloxifene by Cytochrome P450 3A4.” 2010. Doctoral Dissertation, University of Utah. Accessed January 21, 2021. http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1401/rec/288.

MLA Handbook (7^th Edition):

Moore, Chad Douglas. “Dehydrogenation of Raloxifene by Cytochrome P450 3A4.” 2010. Web. 21 Jan 2021.

Vancouver:

Moore CD. Dehydrogenation of Raloxifene by Cytochrome P450 3A4. [Internet] [Doctoral dissertation]. University of Utah; 2010. [cited 2021 Jan 21]. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1401/rec/288.

Council of Science Editors:

Moore CD. Dehydrogenation of Raloxifene by Cytochrome P450 3A4. [Doctoral Dissertation]. University of Utah; 2010. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1401/rec/288

University of Illinois – Urbana-Champaign

2. Frank, Daniel J. Global deconvolution of heterotropic cooperativity in cytochrome P450 3A4.

Degree: PhD, 0318, 2011, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/24520

► Cytochrome P450 3A4 (CYP3A4) plays a central role in xenobiotic metabolism, and is of critical importance to both human health and the pharmaceutical industry. Its… (more)

▼ Cytochrome P450 3A4 (CYP3A4) plays a central role in xenobiotic metabolism, and is of critical importance to both human health and the pharmaceutical industry. Its ability to interact with multiple molecules of the same substrate, or multiple substrates, leads to complex non-Michaelis kinetics, called “homotropic” and “heterotropic” cooperativity respectively. Significant progress has been made towards understanding the enzyme’s complex kinetics by work in our laboratory to isolate the enzyme in Nanodiscs. This provides a homogenous, monodisperse, native-like environment, where the monomeric enzyme is biophysically characterized in the absence of detergent micellar mixtures or liposomal systems which are reported to lead to enzyme heterogeneity and obfuscate its kinetic behavior. Three distinct observable properties which CYP3A4 displays as a result of its reaction cycle are: heme iron spin state, NADPH oxidation rate, and product formation rate. Measuring these three observables as a function of substrate concentration and simultaneously fitting the data sets to a model results in a global analysis of the enzyme’s properties. It reveals the source of homotropic atypical kinetics is not due to any binding cooperativity between the substrates, but rather differences in magnitude of the functional properties from the various enzyme-substrate complexes in solution. To extend this analysis to better understand heterotropic interactions in the system, we generate an interaction surface based upon the linear combination of two substrates kinetic profiles, which corresponds to the absence of any specific heterotropic interactions between them. By comparing the observed behavior of the mixed substrate system to that of the model, we show how two commonly reported heterotropic substrates of CYP3A4 are actually not cooperative, and the observed cooperativity is due to differences in the amplitudes of the functional properties from the various binding intermediates in the system which give rise to the overall observed behavior of the enzyme. Advisors/Committee Members: Sligar, Stephen G. (advisor), Sligar, Stephen G. (Committee Chair), Gerlt, John A. (committee member), Clegg, Robert M. (committee member), Fratti, Rutilio A. (committee member).

Subjects/Keywords: cooperativity; cytochrome P450 3A4; drug-drug interactions

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Frank, D. J. (2011). Global deconvolution of heterotropic cooperativity in cytochrome P450 3A4. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/24520

Chicago Manual of Style (16^th Edition):

Frank, Daniel J. “Global deconvolution of heterotropic cooperativity in cytochrome P450 3A4.” 2011. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed January 21, 2021. http://hdl.handle.net/2142/24520.

MLA Handbook (7^th Edition):

Frank, Daniel J. “Global deconvolution of heterotropic cooperativity in cytochrome P450 3A4.” 2011. Web. 21 Jan 2021.

Vancouver:

Frank DJ. Global deconvolution of heterotropic cooperativity in cytochrome P450 3A4. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2011. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/2142/24520.

Council of Science Editors:

Frank DJ. Global deconvolution of heterotropic cooperativity in cytochrome P450 3A4. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2011. Available from: http://hdl.handle.net/2142/24520

3. Benkaidali, Lydia. Etude et applications de nouveaux modèles géométriques des canaux d'accès au site actif de certains cytochromes P450 humains par des ligands volumineux : Analysis and applications of new geometrical models of active site access channels of some human cytochromes P450 for large ligands.

Degree: Docteur es, Chimie Théorique, 2016, Université Pierre et Marie Curie – Paris VI

URL: http://www.theses.fr/2016PA066377

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Les cytochromes P450s (CYPs) sont des hémoprotéines intervenant dans la fonction de détoxication cellulaire. Le site actif des CYPs est enfoui dans la protéine, mais… (more)

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Les cytochromes P450s (CYPs) sont des hémoprotéines intervenant dans la fonction de détoxication cellulaire. Le site actif des CYPs est enfoui dans la protéine, mais accessible aux ligands par des canaux. A l'aide d'une méthode récente basée sur la triangulation de Delaunay de la protéine, et implémentée dans le logiciel CCCPP, nous avons modélisé géométriquement ces canaux pour plusieurs isoformes humaines, dont le 3A4, présent au niveau du foie humain et responsable de la métabolisation d'un nombre important de médicaments, afin de constituer un filtre stérique destiné au criblage virtuel rapide de chimiothèques. Cette approche nous a permis d'obtenir des informations sur les mécanismes d'ouverture et de fermeture des canaux, permettant d'expliquer comment des ligands volumineux peuvent accéder au site actif. Ces résultats confirment et étendent ceux de la littérature, et peuvent contribuer à l'élaboration de médicaments nouveaux ou ayant moins d'effets secondaires.

The cytochromes P450s (CYPs) are hemoproteins involved in the cellular detoxification function. The CYPs active site is buried inside the protein, but it can be accessed by the ligands through channels. With a recent method based upon the Delaunay triangulation of the protein, and implemented in the CCCPP software, we modelized geometrically these channels for several human isoforms, including the 3A4, located in the human liver and responsible of the metabolization of an important number of drugs, in order to build a sterical filter devoted to high throughput virtual screening of chemical libraries. This approach let us to get information on mechanisms of opening and closing of the channels, allowing to explain how large ligands can access to the active site. These results are in agreement and extend those found in the literature, and can contribute to the design of new drugs or of drugs having less side effects.

Advisors/Committee Members: Petitjean, Michel (thesis director), Maurel, François (thesis director).

Subjects/Keywords: Cytochrome P450; CYP 3A4; Site actif; Cavité; Canal; Triangulation de Delaunay; Channel; CYP 3A4; Cytochrome P450; 541.2

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Benkaidali, L. (2016). Etude et applications de nouveaux modèles géométriques des canaux d'accès au site actif de certains cytochromes P450 humains par des ligands volumineux : Analysis and applications of new geometrical models of active site access channels of some human cytochromes P450 for large ligands. (Doctoral Dissertation). Université Pierre et Marie Curie – Paris VI. Retrieved from http://www.theses.fr/2016PA066377

Chicago Manual of Style (16^th Edition):

Benkaidali, Lydia. “Etude et applications de nouveaux modèles géométriques des canaux d'accès au site actif de certains cytochromes P450 humains par des ligands volumineux : Analysis and applications of new geometrical models of active site access channels of some human cytochromes P450 for large ligands.” 2016. Doctoral Dissertation, Université Pierre et Marie Curie – Paris VI. Accessed January 21, 2021. http://www.theses.fr/2016PA066377.

MLA Handbook (7^th Edition):

Benkaidali, Lydia. “Etude et applications de nouveaux modèles géométriques des canaux d'accès au site actif de certains cytochromes P450 humains par des ligands volumineux : Analysis and applications of new geometrical models of active site access channels of some human cytochromes P450 for large ligands.” 2016. Web. 21 Jan 2021.

Vancouver:

Benkaidali L. Etude et applications de nouveaux modèles géométriques des canaux d'accès au site actif de certains cytochromes P450 humains par des ligands volumineux : Analysis and applications of new geometrical models of active site access channels of some human cytochromes P450 for large ligands. [Internet] [Doctoral dissertation]. Université Pierre et Marie Curie – Paris VI; 2016. [cited 2021 Jan 21]. Available from: http://www.theses.fr/2016PA066377.

Council of Science Editors:

Benkaidali L. Etude et applications de nouveaux modèles géométriques des canaux d'accès au site actif de certains cytochromes P450 humains par des ligands volumineux : Analysis and applications of new geometrical models of active site access channels of some human cytochromes P450 for large ligands. [Doctoral Dissertation]. Université Pierre et Marie Curie – Paris VI; 2016. Available from: http://www.theses.fr/2016PA066377

Texas A&M University

4. Gu, Xinsheng. Regulation of cytochrome P450 3A4 gene expression through modulating pregnane X receptor transcriptional activity by NF-ꢬ aryl hydrocarbon receptor and xenobiotics.

Degree: PhD, Toxicology, 2009, Texas A&M University

URL: http://hdl.handle.net/1969.1/ETD-TAMU-1630

► Cytochrome P450 3A4 (CYP3A4) is a key enzyme responsible for the metabolism of drugs and endogenous compounds in human liver and intestine. CYP3A4 gene expression… (more)

▼ Cytochrome P450 3A4 (CYP3A4) is a key enzyme responsible for the metabolism of drugs and endogenous compounds in human liver and intestine. CYP3A4 gene expression is mainly regulated by Pregnane X receptor (PXR) which is a ligand-dependent nuclear receptor. It is a long-standing observation that inflammatory responses and infections decrease drug metabolism capacity in human and experimental animals. In this study, I reported that NF-κB activation by LPS and TNF-α plays a pivotal role in the suppression of CYP3A4 through interactions of NF-κB with PXR/RXR complex. Inhibition of NF-κB by NF-κB specific suppressor SRIκBα reversed the suppressive effects of LPS and TNF-α. Furthermore, I showed that NF-κB p65 disrupted the association of PXR/RXRα complex with DNA sequences as determined by EMSA and chromatin immunoprecipitation assays. NF-κB p65 directly interacted with DNA binding domain of RXRα and DNA binding domain, hinge domain and ligand-binding domain of PXR and may prevent its binding to the consensus DNA sequences, thus inhibiting the transactivation by PXR/RXRα complex. This mechanism of suppression by NF-κB activation may be extended to other nuclear receptor-regulated systems where RXRα is a dimerization partner. Many genes regulated by PXR and AhR are important for phase I, II and III drug metabolism. In this study I reported a crosstalk between PXR and AhR pathways. AhR physically and functionally interacted with PXR and enhanced the PXR transcriptional activity, and the interaction repressed the AhR transcriptional activity. AhR also physically interacted with RXRα. The synergistic induction of Gsta1 in the liver of mice by PCN and TCDD might assume a different mechanism. The results suggested the metabolism kinetics of mixture drugs was different from and more complicated than that of single compound. Using a HepG2 cell-based PXR-driven CYP3A4-Luciferase assay, I reported that E/F domain of PXR was responsible for ligand-dependant activation. A/B domain was necessary for co-activating the ligand-dependent activation and D domain was suppressive. High doses of Valerian Root extraction were PXR-dependent CYP3A4 inducers. Green tea polyphenols, aflatoxin B1, CuSO4 and MnCl2 enhanced the PXR transcription activity activated by rifampicin. The results suggested PXR-mediated drug metabolism kinetics altered on xenobiotic exposure. Advisors/Committee Members: Tian, Yanan (advisor), Donnelly, Kirby C. (committee member), Porter, Weston W. (committee member), Safe, Stephen H. (committee member).

Subjects/Keywords: cytochrome P450 3A4; Pregnane X Receptor

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gu, X. (2009). Regulation of cytochrome P450 3A4 gene expression through modulating pregnane X receptor transcriptional activity by NF-ꢬ aryl hydrocarbon receptor and xenobiotics. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/ETD-TAMU-1630

Chicago Manual of Style (16^th Edition):

Gu, Xinsheng. “Regulation of cytochrome P450 3A4 gene expression through modulating pregnane X receptor transcriptional activity by NF-ꢬ aryl hydrocarbon receptor and xenobiotics.” 2009. Doctoral Dissertation, Texas A&M University. Accessed January 21, 2021. http://hdl.handle.net/1969.1/ETD-TAMU-1630.

MLA Handbook (7^th Edition):

Gu, Xinsheng. “Regulation of cytochrome P450 3A4 gene expression through modulating pregnane X receptor transcriptional activity by NF-ꢬ aryl hydrocarbon receptor and xenobiotics.” 2009. Web. 21 Jan 2021.

Vancouver:

Gu X. Regulation of cytochrome P450 3A4 gene expression through modulating pregnane X receptor transcriptional activity by NF-ꢬ aryl hydrocarbon receptor and xenobiotics. [Internet] [Doctoral dissertation]. Texas A&M University; 2009. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-1630.

Council of Science Editors:

Gu X. Regulation of cytochrome P450 3A4 gene expression through modulating pregnane X receptor transcriptional activity by NF-ꢬ aryl hydrocarbon receptor and xenobiotics. [Doctoral Dissertation]. Texas A&M University; 2009. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-1630

5. Choy, Alison Pui Ki. Prediction of metabolic stability and bioavailability with bioisosteric replacements.

Degree: PhD, 2018, University of Cambridge

URL: https://doi.org/10.17863/CAM.26167 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.753416

► Drug development is a long and expensive process. Potential drug candidates can fail clinical trials due to numerous issues, including metabolic stability and efficacy issues,… (more)

Subjects/Keywords: 615.7; Sites of metabolism prediction; QSAR; Bioisostere; Bioavailability; Cytochrome P450 3A4; P-Glycoprotein

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Choy, A. P. K. (2018). Prediction of metabolic stability and bioavailability with bioisosteric replacements. (Doctoral Dissertation). University of Cambridge. Retrieved from https://doi.org/10.17863/CAM.26167 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.753416

Chicago Manual of Style (16^th Edition):

Choy, Alison Pui Ki. “Prediction of metabolic stability and bioavailability with bioisosteric replacements.” 2018. Doctoral Dissertation, University of Cambridge. Accessed January 21, 2021. https://doi.org/10.17863/CAM.26167 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.753416.

MLA Handbook (7^th Edition):

Choy, Alison Pui Ki. “Prediction of metabolic stability and bioavailability with bioisosteric replacements.” 2018. Web. 21 Jan 2021.

Vancouver:

Choy APK. Prediction of metabolic stability and bioavailability with bioisosteric replacements. [Internet] [Doctoral dissertation]. University of Cambridge; 2018. [cited 2021 Jan 21]. Available from: https://doi.org/10.17863/CAM.26167 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.753416.

Council of Science Editors:

Choy APK. Prediction of metabolic stability and bioavailability with bioisosteric replacements. [Doctoral Dissertation]. University of Cambridge; 2018. Available from: https://doi.org/10.17863/CAM.26167 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.753416

North-West University

6. Mgwabi, Mthokozisi Muziwandile Nkosingiphile. Genetic polymorphism in dextromethorphan metabolism by CYP2D6 and CYP3A4 enzyme isoforms / Mthokozisi Muziwandile Nkosingiphile Mgwabi .

Degree: 2003, North-West University

URL: http://hdl.handle.net/10394/163

► Most administered drugs are metabolised in the liver by Phase I enzymes and more importantly by the cytochrome P450 (CYP) system. The extent of first-pass… (more)

▼ Most administered drugs are metabolised in the liver by Phase I enzymes and more importantly by the cytochrome P450 (CYP) system. The extent of first-pass metabolism is important in determining whether the drug will have therapeutic or adverse effects after being administered to a patient. To date the CYP family has been shown to consist of 74 families denoted as CYPl to CYP118, and only a few families are significantly involved in drug metabolism. CYP3A4 is the most important isoenzyme followed by CYP2D6, CYP2C9, and CYP2C19 with a small contribution by CYP2E1, CYP2A6, and CYPlA4. CYP2D6 and CYP3A4 enzyme isoforms have been well established to exhibit interethnic and interindividual variability with regard to drug metabolising capacity. Mutation on the gene coding for a metabolising enzyme is a major cause of variation in drug metabolism. This mutation gives rise to allelic variants producing enzymes with altered metabolising activity. The presence of an allele with decreased metabolic activity in an individual gives rise to the poor metabolising (PM) phenotype. When the PM phenotype occurs at a frequency of more than 1% within a given population, then the term genetic polymorphism applies. The aberrant metabolic capacity translates into variable drug responses of more than 20-fold, leading to different susceptibility to sub-therapeutic effects or adverse drug reactions. A significant number of drugs, such as the B-adrenergic blockers, antidepressants, antipsychotic and antiarrhythmic agents, are entirely or partly metabolised by CYP2D6 and CYP3A4. Genetic polymorphism is especially important for drugs with a narrow therapeutic/toxicity window. Phenotyping involves the use of a probe drug that is administered to the subject, followed by determination of the parent drug and its metabolites in the urine. The aim of this study was to develop and validate an HPLC method for phenotypic determination of the CYP3A4 and CYP2D6 enzymes, followed by the application of the assay in a random heterogeneous population of males. Dextromethorphan (DXM) was used as an in vivo probe for simultaneous determination of the phenotypic expression of CYP2D6 and CYP3A4. An HPLC method coupled with a fluorescence detector was developed for the phenotypic determination of CYP2D6 and CYP3A4 iso-enzymes as determined by the concentration of dextromethorphan/dextrophan (DXM/DX) and dextromethorphan/3methoxy-morphinan (DXM/3MM) metabolic ratios respectively. The compounds were separated on a phenyl column (150 x 4,6 mm, 5-um particle size) serially connected to nitrile column (250 x 4,6 mm, 5-um particle size) using mobile phase of 80% (1.5% glacial acetic acid and 0.1% triethyl amine in distilled water) and 20% acetonitrile. Solid phase extraction was used to extract the analytes from urine samples using silica cartridges. The suitability of the method was demonstrated in a preliminary study with sixteen healthy Caucasian males. After a single oral 30 mg DXM dose, the volunteers were required to collect all urine samples voided 8 hours post oral…

Subjects/Keywords: HPLC; Cytochrome P450 2D6 (CYP2D6); Cytochrome P450 3A4 (CYP3A4); Dextromethorphan; Metabolism; Phenotyping

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APA (6^th Edition):

Mgwabi, M. M. N. (2003). Genetic polymorphism in dextromethorphan metabolism by CYP2D6 and CYP3A4 enzyme isoforms / Mthokozisi Muziwandile Nkosingiphile Mgwabi . (Thesis). North-West University. Retrieved from http://hdl.handle.net/10394/163

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Mgwabi, Mthokozisi Muziwandile Nkosingiphile. “Genetic polymorphism in dextromethorphan metabolism by CYP2D6 and CYP3A4 enzyme isoforms / Mthokozisi Muziwandile Nkosingiphile Mgwabi .” 2003. Thesis, North-West University. Accessed January 21, 2021. http://hdl.handle.net/10394/163.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Mgwabi, Mthokozisi Muziwandile Nkosingiphile. “Genetic polymorphism in dextromethorphan metabolism by CYP2D6 and CYP3A4 enzyme isoforms / Mthokozisi Muziwandile Nkosingiphile Mgwabi .” 2003. Web. 21 Jan 2021.

Vancouver:

Mgwabi MMN. Genetic polymorphism in dextromethorphan metabolism by CYP2D6 and CYP3A4 enzyme isoforms / Mthokozisi Muziwandile Nkosingiphile Mgwabi . [Internet] [Thesis]. North-West University; 2003. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/10394/163.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Mgwabi MMN. Genetic polymorphism in dextromethorphan metabolism by CYP2D6 and CYP3A4 enzyme isoforms / Mthokozisi Muziwandile Nkosingiphile Mgwabi . [Thesis]. North-West University; 2003. Available from: http://hdl.handle.net/10394/163

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Western Ontario

7. Woolsey, Sarah J. Cytochrome P450 3A4 Expression and Regulation in Non-Alcoholic Fatty Liver Disease.

Degree: 2015, University of Western Ontario

URL: https://ir.lib.uwo.ca/etd/3355

► Non-alcoholic fatty liver disease (NAFLD) is defined as lipid accumulation within hepatocytes (steatosis) in the absence of excess alcohol consumption. It is the most common… (more)

▼ Non-alcoholic fatty liver disease (NAFLD) is defined as lipid accumulation within hepatocytes (steatosis) in the absence of excess alcohol consumption. It is the most common liver disease in the western world, affecting one third of the general adult population with particularly high prevalence in obesity and type 2 diabetes. NAFLD is a disease continuum originating with simple hepatic steatosis that can progress to non-alcoholic steatohepatitis (NASH) with fibrosis and potentially cirrhosis, which places patients at risk for hepatocellular carcinoma. Unfortunately, there are not yet specific pharmacologic agents to treat NAFLD and so its management involves treatment of comorbidities, but there are significant efforts to develop new drugs to reverse disease course and prevent progression. While the liver is the major organ of drug elimination, little is known regarding the effect of NAFLD on hepatic drug metabolism in humans. The most important drug metabolizing enzyme is cytochrome P450 (CYP) 3A4, which metabolizes medications widely prescribed in NAFLD patients including those to treat hypertension, type 2 diabetes and dyslipidemia. We tested the hypothesis that CYP3A4 expression and activity are altered in NAFLD. In the first study, we evaluated the use of predictive endogenous plasma biomarkers of drug metabolic function against the gold-standard midazolam pharmacokinetic phenotyping approach for the assessment of constitutive CYP3A activity in healthy subjects. There was a lack of association between levels of the CYP3A derived metabolites 4β-hydroxycholesterol and 6β-hydroxycortisol with midazolam pharmacokinetics indicating that these biomarkers have limited utility within the context of relatively narrow enzyme activity variability in healthy individuals. CYP3A activity was next examined in patients with biopsy-proven NAFLD in comparison to healthy control subjects using midazolam pharmacokinetic phenotyping and biomarker approaches. We demonstrated, for the first time, that in vivo CYP3A activity is reduced in patients with simple steatosis or NASH and that fibrosis was also associated with lower enzyme function. Likewise, experimental NAFLD in mice and cultured hepatoma cells was associated with lower CYP3A4 expression. In the third study, mouse and cell models of NAFLD were used to define a novel regulatory pathway involved in the observed reduction of CYP3A4 expression and activity. We found that NAFLD causes hepatic upregulation of the metabolic hormone, fibroblast growth factor 21 (FGF21), stimulating a canonical cellular phospho-signaling pathway. FGF21 acted on the liver to decrease the nuclear localization and activity of the pregnane X receptor, a key transcriptional regulator of CYP3A4 gene expression. These findings provide novel insights to altered drug metabolism in NAFLD and a mechanistic basis for studies aimed to optimize pharmacotherapy and drug development for this common liver disease.

Subjects/Keywords: Non-alcoholic fatty liver disease; Cytochrome P450 3A4; Drug metabolism; Gene regulation; Fibroblast growth factor 21; Pregnane x receptor; Diseases; Pharmacology

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APA (6^th Edition):

Woolsey, S. J. (2015). Cytochrome P450 3A4 Expression and Regulation in Non-Alcoholic Fatty Liver Disease. (Thesis). University of Western Ontario. Retrieved from https://ir.lib.uwo.ca/etd/3355

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Woolsey, Sarah J. “Cytochrome P450 3A4 Expression and Regulation in Non-Alcoholic Fatty Liver Disease.” 2015. Thesis, University of Western Ontario. Accessed January 21, 2021. https://ir.lib.uwo.ca/etd/3355.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Woolsey, Sarah J. “Cytochrome P450 3A4 Expression and Regulation in Non-Alcoholic Fatty Liver Disease.” 2015. Web. 21 Jan 2021.

Vancouver:

Woolsey SJ. Cytochrome P450 3A4 Expression and Regulation in Non-Alcoholic Fatty Liver Disease. [Internet] [Thesis]. University of Western Ontario; 2015. [cited 2021 Jan 21]. Available from: https://ir.lib.uwo.ca/etd/3355.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Woolsey SJ. Cytochrome P450 3A4 Expression and Regulation in Non-Alcoholic Fatty Liver Disease. [Thesis]. University of Western Ontario; 2015. Available from: https://ir.lib.uwo.ca/etd/3355

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Texas – Austin

8. -0507-6023. A mechanistic study of how hepatic cytochrome P450 3A4 is regulated during infectious and non-infectious conditions.

Degree: PhD, Pharmaceutical Sciences, 2018, University of Texas – Austin

URL: http://hdl.handle.net/2152/63382

► It has been established that adenovirus infection alters the expression and function of hepatic cytochrome P450 3A (CYP3A) for 14 days in several animal models.… (more)

▼ It has been established that adenovirus infection alters the expression and function of hepatic cytochrome P450 3A (CYP3A) for 14 days in several animal models. To determine the mechanism behind adenovirus-mediated alterations in CYP3A4 and if this effect was relevant to humans, we characterized a human hepatocyte cell line, HC-04, as an in vitro model to study virus-mediated changes in human CYP3A4. Similar to in vivo observations, infection with a first-generation recombinant adenovirus (AdlacZ) significantly suppressed CYP3A4 catalytic activity in an isoform-specific manner in this cell line. HC-04 cells were subsequently used to determine how vaccines to be used in pandemic outbreaks impact CYP3A4 expression and function. Infection with a recombinant adenovirus-based Ebola vaccine or influenza A virus subtypes H1N1 and H3N2 significantly suppressed human hepatic CYP3A4 catalytic activity by 34%, 91%, and 90%, respectively. This effect is important to understand as these vaccines are given to people of all ages. Mechanistic study of adenovirus infection in HC-04 cells indicated that engagement of integrin receptors is key in the initiation of processes responsible for changes in CYP3A4 during infection. Mice infected with AdlacZ experienced a 70% reduction in CYP3A activity 24 hours after infection. While infection with a mutant virus with integrin-binding arginine-glycine-aspartic acid (RGD) sequences deleted from the viral capsid (AdΔRGD) did not alter CYP3A activity at the same timepoint. CYP3A mRNA and protein levels in AdlacZ-treated animals were also suppressed, whereas those of mice given AdΔRGD were similar to uninfected control mice. Silencing of the integrin β-subunit reverted adenovirus-mediated CYP3A4 suppression in vitro. Silencing of the α-subunit did not. This led us to believe that interactions with the -tail of the integrin receptor is important for virus-mediated suppression of CYP3A4. Talin-1, a cytoplasmic protein that specifically binds to the -tail of integrins therefore became the focus of remaining studies. Knockdown of talin-1 increased CYP3A4 catalytic activity by 190%. Genes associated with post-translational modifications (PTMs) were downregulated in talin-silenced samples and analysis during viral infection revealed a significant increase in PTMs of CYP3A4. These initial experiments indicate a role of talin-1 and PTMs in the regulation of CYP3A4, however further experiments are needed to confirm these findings. Understanding changes in CYP3A4 during wild-type infection and immunization is clinically important, especially for low metabolizers. In this population, suppression of CYP3A4 could lead to accumulation of drugs that normally would be metabolized and cleared via this pathway, leading to serious therapeutic failure or adverse effects. Advisors/Committee Members: Croyle, Maria A. (advisor), Davis, Patrick J (committee member), Ghose, Romi (committee member), Ghosh, Debadyuti (committee member), Stavchansky, Salomon A (committee member).

Subjects/Keywords: Drug metabolism; Cytochrome P450 3A4; Liver; Integrins: Adenovirus; Influenza A virus; Talin-1; Post-translational modifications

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APA (6^th Edition):

-0507-6023. (2018). A mechanistic study of how hepatic cytochrome P450 3A4 is regulated during infectious and non-infectious conditions. (Doctoral Dissertation). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/63382

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Chicago Manual of Style (16^th Edition):

-0507-6023. “A mechanistic study of how hepatic cytochrome P450 3A4 is regulated during infectious and non-infectious conditions.” 2018. Doctoral Dissertation, University of Texas – Austin. Accessed January 21, 2021. http://hdl.handle.net/2152/63382.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

MLA Handbook (7^th Edition):

-0507-6023. “A mechanistic study of how hepatic cytochrome P450 3A4 is regulated during infectious and non-infectious conditions.” 2018. Web. 21 Jan 2021.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Vancouver:

-0507-6023. A mechanistic study of how hepatic cytochrome P450 3A4 is regulated during infectious and non-infectious conditions. [Internet] [Doctoral dissertation]. University of Texas – Austin; 2018. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/2152/63382.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Council of Science Editors:

-0507-6023. A mechanistic study of how hepatic cytochrome P450 3A4 is regulated during infectious and non-infectious conditions. [Doctoral Dissertation]. University of Texas – Austin; 2018. Available from: http://hdl.handle.net/2152/63382

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

University of Western Ontario

9. Wilson, Aze. Drug Response And Metabolism In Crohn's Disease.

Degree: 2018, University of Western Ontario

URL: https://ir.lib.uwo.ca/etd/5557

► Inflammatory bowel disease (IBD) is an illness of chronic intestinal inflammation comprised of Crohn's disease (CD) and ulcerative colitis (UC). Specialists rely heavily on drugs… (more)

▼ Inflammatory bowel disease (IBD) is an illness of chronic intestinal inflammation comprised of Crohn's disease (CD) and ulcerative colitis (UC). Specialists rely heavily on drugs that target a dysregulated immune system. There is a staggering degree of variation in drug response in CD. Our understanding of drug metabolism and response in IBD is limited. Gaining new insights into IBD-specific modifications of drug metabolism may allow for improved drug efficacy and reduced toxicity. Cytochrome P450 (CYP) 3A4 is the most relevant determinant of drug metabolism and exposure for medications prescribed today. CYP3A4 is highly expressed in the liver, but is also important to intestinal drug metabolism. Little is known about CYP3A4 activity in disease states. We tested the hypothesis that CD affects the activity, expression and regulation of CYP3A4. Acute, non-hepatic inflammatory states are reported to reduce hepatic CYP3A4 activity. Using midazolam pharmacokinetics and the cholesterol metabolite, 4β- hydroxycholesterol as in vivo probes of CYP3A4 activity, we were able to demonstrate and confirm that CYP3A4 activity is lower in CD. Conversely, we were unable to show, using in vitro modeling, that differences in CYP3A4 activity were due to differential nuclear receptor-signaling in CD. CYP3A4 plays a key role in hepatic and intestinal first-pass metabolism, likely in concert with the xenobiotic exporter, P-glycoprotein (P-gp). The intestinal and colonic ii expression of CYP3A4 in CD has not been well characterized. Using an immunobloting technique, we were able to demonstrate that the intestinal and colonic expression of CYP3A4 are reduced in CD. Lastly, nuclear receptors such as FXR and PXR are important regulators of CYP3A4. Both are down-regulated in IBD. This may have important consequences for drug response in IBD. We confirm that a novel single nucleotide polymorphism in FXR results in a reduction in its downstream products in vivo and reveal a link between genetic variation in FXR and outcomes of CD severity, such as risk and time to surgery, particularly relevant to women affected by CD. Ultimately, these studies demonstrate the impact of CD on drug metabolism pathways and offer insight into the overlap between CD pathogenesis and drug metabolism.

Subjects/Keywords: Crohn's disease; drug metabolism; farnesoid X receptor; pregnane X receptor; cytochrome P450 3A4; pharmacokinetics; Digestive System Diseases; Gastroenterology; Medical Pharmacology; Medicine and Health Sciences; Translational Medical Research

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APA (6^th Edition):

Wilson, A. (2018). Drug Response And Metabolism In Crohn's Disease. (Thesis). University of Western Ontario. Retrieved from https://ir.lib.uwo.ca/etd/5557

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wilson, Aze. “Drug Response And Metabolism In Crohn's Disease.” 2018. Thesis, University of Western Ontario. Accessed January 21, 2021. https://ir.lib.uwo.ca/etd/5557.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wilson, Aze. “Drug Response And Metabolism In Crohn's Disease.” 2018. Web. 21 Jan 2021.

Vancouver:

Wilson A. Drug Response And Metabolism In Crohn's Disease. [Internet] [Thesis]. University of Western Ontario; 2018. [cited 2021 Jan 21]. Available from: https://ir.lib.uwo.ca/etd/5557.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wilson A. Drug Response And Metabolism In Crohn's Disease. [Thesis]. University of Western Ontario; 2018. Available from: https://ir.lib.uwo.ca/etd/5557

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of the Western Cape

10. Feleni, Usisipho. Palladium telluride quantum dots biosensor for the determination of indinavir drug .

Degree: 2013, University of the Western Cape

URL: http://hdl.handle.net/11394/3504

► Indinavir is a potent and well tolerated protease inhibitor drug used as a component of the highly active antiretroviral therapy (HAART) of HIV/AIDS, which results… (more)

▼ Indinavir is a potent and well tolerated protease inhibitor drug used as a component of the highly active antiretroviral therapy (HAART) of HIV/AIDS, which results in pharmacokinetics that may be favourable or adverse. These drugs work by maintaining a plasma concentration that is sufficient to inhibit viral replication and thereby suppressing a patient’s viral load. A number of antiretroviral drugs, including indinavir, undergo metabolism that is catalysed by cytochrome P450-3A4 enzyme found in the human liver microsomes. The rate of drug metabolism influences a patient’s response to treatment as well as drug interactions that may lead to life-threatening toxic conditions, such as haemolytic anaemia, kidney failure and liver problems. Therapeutic drug monitoring (TDM) during HIV/AIDS treatment has been suggested to have a potential to reduce drug toxicity and optimise individual therapy. A fast and reliable detection technique, such as biosensing, is therefore necessary for the determination of a patient’s metabolic profile for indinavir and for appropriate dosing of the drugs. In this study biosensors developed for the determination of ARV drugs comprised of cysteamine self-assembled on a gold electrode, on which was attached 3-mercaptopropionic acid-capped palladium telluride (3-MPA-PdTe) or thioglycolic acid-capped palladium telluride (TGA-PdTe) quantum dots that are cross-linked to cytochrome P450-3A4 (CYP3A4) in the presence of 1-ethyl-3(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide. The quantum dots were synthesized in the presence of capping agents (3-MPA or TGA) to improve their stability, solubility and biocompatibility. The capping of PdTe quantum dots with TGA or 3-MPA was confirmed by FTIR, where the SH group absorption band disappeared from the spectra of 3-MPA-PdTe and TGA-PdTe. The particle size of the quantum dots (< 5 nm) was estimated from high resolution transmission electron microscopy (HRTEM) measurements. Optical properties of the materials were confirmed by UV-Vis spectrophotometry which produced absorption iii bands at ~320 nm that corresponded to energy band gap values of 3 eV (3.87 eV) for TGAPdTe (3-MPA-PdTe) quantum dots. The electrocatalytic properties of the quantum dots biosensor systems were studied by cyclic voltammetry (CV) for which the characteristic reduction peak at 0.75 V was used to detect the response of the biosensor to indinavir. Results for indinavir biosensor constructed with 3-MPA-SnSe quantum dots are also reported in this thesis. The three biosensors systems were very sensitive towards indinavir; and gave low limits of detection (LOD) values of 3.22, 4.3 and 6.2 ng/mL for 3-MPA-SnSe, 3-MPA-PdTe and TGA-PdTe quantum dots biosensors, respectively. The LOD values are within the ‘maximum plasma concentration’ (Cmax) value of indinavir (5 - 15 ng/mL) normally observed 8 h after drug intake. Advisors/Committee Members: Iwuoha, Emmanuel (advisor).

Subjects/Keywords: Indinavir drug; Cytochrome P450-3A4 (CYP3A4); Quantum dots; Self-assembled monolayers; Biosensors; Cyclic voltammetry; Limit of detection (LOD); Therapeutic drug monitoring (TDM)

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APA (6^th Edition):

Feleni, U. (2013). Palladium telluride quantum dots biosensor for the determination of indinavir drug . (Thesis). University of the Western Cape. Retrieved from http://hdl.handle.net/11394/3504

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Feleni, Usisipho. “Palladium telluride quantum dots biosensor for the determination of indinavir drug .” 2013. Thesis, University of the Western Cape. Accessed January 21, 2021. http://hdl.handle.net/11394/3504.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Feleni, Usisipho. “Palladium telluride quantum dots biosensor for the determination of indinavir drug .” 2013. Web. 21 Jan 2021.

Vancouver:

Feleni U. Palladium telluride quantum dots biosensor for the determination of indinavir drug . [Internet] [Thesis]. University of the Western Cape; 2013. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/11394/3504.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Feleni U. Palladium telluride quantum dots biosensor for the determination of indinavir drug . [Thesis]. University of the Western Cape; 2013. Available from: http://hdl.handle.net/11394/3504

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

RMIT University

11. Liu, Y. A bioinformatic and cell-based study on the mutation and regulation of human nuclear receptors and their target genes.

Degree: 2010, RMIT University

URL: http://researchbank.rmit.edu.au/view/rmit:160620

► Human nuclear receptor (NR) superfamily represents an important group of regulating factors of a large number of physiologically important target genes. In this project, we… (more)

▼ Human nuclear receptor (NR) superfamily represents an important group of regulating factors of a large number of physiologically important target genes. In this project, we hypothesized that the phenotype of non-synonymous single nucleotide polymorphisms (nsSNPs) of NRs and their target genes could be predicted using computational approaches and that herbal compounds regulated CYP3A4 via pregnane X receptor (PXR) mediated pathway. To test this hypothesis: Firstly, we employed SIFT and PolyPhen to predict the impact of 442 nsSNPs in 48 human NR genes on NR activities and disease susceptibility. Of 442 nsSNPs, 289 (65.38%) were classified as â€œintolerantâ€ by SIFT and 269 (60.86%) were classified as â€œprobably damagingâ€ or â€œpossibly damagingâ€ by PolyPhen respectively. The results from the two algorithms were in concordance. Among the 442 mutations, 229 of them have been functionally characterized. SIFT gave a correct prediction rate of 83.84%, while PolyPhen gave a prediction rate of 76.86%. These results indicate that both SIFT and PolyPhen are useful and efficient tools to predict the functional effects of nsSNPs of human NR genes. Secondly, we predict the phenotypical impact of 1632 nsSNPs from human ABC transporter genes. Using the PolyPhen and SIFT, 41.8-53.6% of nsSNPs in ABC transporter genes were predicted to have an impact on protein function. The prediction accuracy was up to 63-85% when compared with known phenotypical data. Of nsSNPs predicted as deleterious, the prediction scores by SIFT and PolyPhen were significantly related to the number of nsSNPs with known phenotypes confirmed by experimental and human studies. Finally, we investigated the effect of an array of compounds isolated from commonly used Chinese herbal medicines on the activity of PXR in transiently transfected HepG2 and Huh7 cells and on the expression of PXR and CYP3A4 in human intestinal LS174T cells. The study found that praeruptorin A and C, salvianolic acid B, sodium danshensu, and protocatechuic aldehyde, cryptotanshinone, emodin, morin, and tanshinone IIA significantly transactivated the CYP3A4 reporter gene construct in HepG2 cells or Huh7 cells. The PXR mRNA expression in LS174T cells was significantly induced by physcion, protocatechuic aldehyde, salvianolic acid B, and sodium danshensu. However, epifriedelanol, morin, praeruptorin D, mulberroside A, tanshinone I, and tanshinone IIA significantly down-regulated the expression of PXR mRNA in LS174T cells. Furthermore, emodin, physcion, praeruptorin C and E, protocatechuic aldehyde, rhein, salvianolic acid B, and sodium danshensu significantly induced CYP3A4 mRNA expression in human intestinal LS174T cells. These findings suggest that: a) predicting the phenotypic consequence of nsSNPs in human NRs and their target genes ABC transporters using computational algorithms may provide further understanding of genetic differences in susceptibility to diseases and drug response and would be useful hints for further genotype-phenotype studies; and b) herbal…

Subjects/Keywords: Fields of Research; Nuclear Receptor; Pregnane X Receptor (PXR); Cytochrome P450 3A4 (CYP3A4); Single Nucleotide Polymorphism (SNP); non-synonymous SNP; ATP-Binding Cassette (ABC) Transporters; Sorting Intolerant from Tolerant (SIFT); Polymorphism Phenotyping (PolyPhen); Target Gene; Chinese Herbal Medicine; Herb-Drug Interaction

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Liu, Y. (2010). A bioinformatic and cell-based study on the mutation and regulation of human nuclear receptors and their target genes. (Thesis). RMIT University. Retrieved from http://researchbank.rmit.edu.au/view/rmit:160620

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Liu, Y. “A bioinformatic and cell-based study on the mutation and regulation of human nuclear receptors and their target genes.” 2010. Thesis, RMIT University. Accessed January 21, 2021. http://researchbank.rmit.edu.au/view/rmit:160620.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Liu, Y. “A bioinformatic and cell-based study on the mutation and regulation of human nuclear receptors and their target genes.” 2010. Web. 21 Jan 2021.

Vancouver:

Liu Y. A bioinformatic and cell-based study on the mutation and regulation of human nuclear receptors and their target genes. [Internet] [Thesis]. RMIT University; 2010. [cited 2021 Jan 21]. Available from: http://researchbank.rmit.edu.au/view/rmit:160620.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Liu Y. A bioinformatic and cell-based study on the mutation and regulation of human nuclear receptors and their target genes. [Thesis]. RMIT University; 2010. Available from: http://researchbank.rmit.edu.au/view/rmit:160620

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Université de Montréal

12. Fleury, Isabelle. Polymorphismes dans des gènes de métabolisme des corticostéroïdes : rôle dans la réponse thérapeutique.

Degree: 2004, Université de Montréal

URL: http://hdl.handle.net/1866/14201

Subjects/Keywords: Pharmacogénétique; Leucémie lymphoblastique aiguë; Récepteur des glucocorticoïdes; Cytochrome P450 3A4; Bcl I; Arg23Lys; Asn363Ser; A-290G

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APA (6^th Edition):

Fleury, I. (2004). Polymorphismes dans des gènes de métabolisme des corticostéroïdes : rôle dans la réponse thérapeutique. (Thesis). Université de Montréal. Retrieved from http://hdl.handle.net/1866/14201

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Fleury, Isabelle. “Polymorphismes dans des gènes de métabolisme des corticostéroïdes : rôle dans la réponse thérapeutique.” 2004. Thesis, Université de Montréal. Accessed January 21, 2021. http://hdl.handle.net/1866/14201.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Fleury, Isabelle. “Polymorphismes dans des gènes de métabolisme des corticostéroïdes : rôle dans la réponse thérapeutique.” 2004. Web. 21 Jan 2021.

Vancouver:

Fleury I. Polymorphismes dans des gènes de métabolisme des corticostéroïdes : rôle dans la réponse thérapeutique. [Internet] [Thesis]. Université de Montréal; 2004. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/1866/14201.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Fleury I. Polymorphismes dans des gènes de métabolisme des corticostéroïdes : rôle dans la réponse thérapeutique. [Thesis]. Université de Montréal; 2004. Available from: http://hdl.handle.net/1866/14201

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of the Western Cape

13. Michira, Immaculate Nyambura. Synthesis, electrodynamics and biosensor applications of novel sulphonated polyaniline nanocomposites .

Degree: 2007, University of the Western Cape

URL: http://hdl.handle.net/11394/2290

► The overall aim of this thesis was to prepare nanostructured more processable heteronuclear sulphonated polyanyline nanocomposites with electroconductive properties suitable for applications in biosensors. The… (more)

Subjects/Keywords: Sulphonated polyaniline nanocomposites; Anthracene sulphonic acid; Horseradish peroxidase; Cytochrome P450 3A4; Erythromycin; Diazinon; N-demethylation; Cyclic voltammetry; Biosensor

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APA (6^th Edition):

Michira, I. N. (2007). Synthesis, electrodynamics and biosensor applications of novel sulphonated polyaniline nanocomposites . (Thesis). University of the Western Cape. Retrieved from http://hdl.handle.net/11394/2290

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Michira, Immaculate Nyambura. “Synthesis, electrodynamics and biosensor applications of novel sulphonated polyaniline nanocomposites .” 2007. Thesis, University of the Western Cape. Accessed January 21, 2021. http://hdl.handle.net/11394/2290.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Michira, Immaculate Nyambura. “Synthesis, electrodynamics and biosensor applications of novel sulphonated polyaniline nanocomposites .” 2007. Web. 21 Jan 2021.

Vancouver:

Michira IN. Synthesis, electrodynamics and biosensor applications of novel sulphonated polyaniline nanocomposites . [Internet] [Thesis]. University of the Western Cape; 2007. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/11394/2290.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Michira IN. Synthesis, electrodynamics and biosensor applications of novel sulphonated polyaniline nanocomposites . [Thesis]. University of the Western Cape; 2007. Available from: http://hdl.handle.net/11394/2290

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of the Western Cape

14. Jijana, Abongile Nwabisa. Development of electrochemical ZnSe Quantam dots biosensors for low-level detection of 17β-Estradiol estrogenic endocrine disrupting compound .

Degree: 2010, University of the Western Cape

URL: http://hdl.handle.net/11394/2310

► The main thesis hub was on development of two electrochemical biosensors for the determination of 17β-estradiol-estradiol: an estrogenic endocrine disrupting compound. Endocronology have significantly shown… (more)

Subjects/Keywords: Electrochemical biosensors; Cytochrome P450-3A4 (CYP3A4); Horseradish peroxidase (HRP); ZnSe quantum dots; Conducting polymers; Cyclic voltammetry (CV); Differential-pulse voltammetry (DPV); 17- estradiol; 17Î±-ethnylestradiol; Estrogenic Endocrine Disrupting Compounds (e-EDC); Michaelis Menten constant; Hydroxylation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Jijana, A. N. (2010). Development of electrochemical ZnSe Quantam dots biosensors for low-level detection of 17β-Estradiol estrogenic endocrine disrupting compound . (Thesis). University of the Western Cape. Retrieved from http://hdl.handle.net/11394/2310

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Jijana, Abongile Nwabisa. “Development of electrochemical ZnSe Quantam dots biosensors for low-level detection of 17β-Estradiol estrogenic endocrine disrupting compound .” 2010. Thesis, University of the Western Cape. Accessed January 21, 2021. http://hdl.handle.net/11394/2310.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Jijana, Abongile Nwabisa. “Development of electrochemical ZnSe Quantam dots biosensors for low-level detection of 17β-Estradiol estrogenic endocrine disrupting compound .” 2010. Web. 21 Jan 2021.

Vancouver:

Jijana AN. Development of electrochemical ZnSe Quantam dots biosensors for low-level detection of 17β-Estradiol estrogenic endocrine disrupting compound . [Internet] [Thesis]. University of the Western Cape; 2010. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/11394/2310.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Jijana AN. Development of electrochemical ZnSe Quantam dots biosensors for low-level detection of 17β-Estradiol estrogenic endocrine disrupting compound . [Thesis]. University of the Western Cape; 2010. Available from: http://hdl.handle.net/11394/2310

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Open Access Theses and Dissertations