LIVIVO - Search results -

Search results

Result 1 - 10 of total 19

Search options

Article ; Online: Perspectives on gender parity in bioanalysis: an interview with Scott Summerfield.

Summerfield, Scott G

Bioanalysis

2019 Volume 11, Issue 7, Page(s) 675–676

Abstract: Biography Having studied for a PhD and postdoctoral fellowship in proteomics Scott moved into the field of regulated Bioanalysis in 1997 when joining SmithKline Beecham. In 2001, Scott moved to Neuroscience Drug Discovery to lead a bioanalytical team ... ...

Abstract	Biography Having studied for a PhD and postdoctoral fellowship in proteomics Scott moved into the field of regulated Bioanalysis in 1997 when joining SmithKline Beecham. In 2001, Scott moved to Neuroscience Drug Discovery to lead a bioanalytical team supporting PK,
MeSH term(s)	Career Choice ; Career Mobility ; Chemistry, Analytic ; Commerce ; Decision Making ; Gender Identity ; Humans
Language	English
Publishing date	2019-04-18
Publishing country	England
Document type	Interview
ISSN	1757-6199
ISSN (online)	1757-6199
DOI	10.4155/bio-2019-0073
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Free Drug Theory - No Longer Just a Hypothesis?

Summerfield, Scott G / Yates, James W T / Fairman, David A

Pharmaceutical research

2022 Volume 39, Issue 2, Page(s) 213–222

Abstract: The Free Drug Hypothesis is a well-established concept within the scientific lexicon pervading many areas of Drug Discovery and Development, and yet it is poorly defined by virtue of many variations appearing in the literature. Clearly, unbound drug is ... ...

Abstract	The Free Drug Hypothesis is a well-established concept within the scientific lexicon pervading many areas of Drug Discovery and Development, and yet it is poorly defined by virtue of many variations appearing in the literature. Clearly, unbound drug is in dynamic equilibrium with respect to absorption, distribution, metabolism, elimination, and indeed, interaction with the desired pharmacological target. Binding interactions be they specific (e.g. high affinity) or nonspecific (e.g. lower affinity/higher capacity) are governed by the same fundamental physicochemical tenets including Hill-Langmuir Isotherms, the Law of Mass Action and Drug Receptor Theory. With this in mind, it is time to recognise a more coherent version and consider it the Free Drug Theory and a hypothesis no longer. Today, we have the experimental and modelling capabilities, pharmacological knowledge, and an improved understanding of unbound drug distribution (e.g. Kp
MeSH term(s)	Animals ; Drug Development ; Drug Discovery ; Humans ; Models, Biological ; Molecular Targeted Therapy ; Network Pharmacology ; Pharmaceutical Preparations/blood ; Pharmaceutical Preparations/metabolism ; Pharmacokinetics ; Protein Binding ; Signal Transduction
Chemical Substances	Pharmaceutical Preparations
Language	English
Publishing date	2022-02-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	843063-9
ISSN	1573-904X ; 0724-8741 ; 0739-0742
ISSN (online)	1573-904X
ISSN	0724-8741 ; 0739-0742
DOI	10.1007/s11095-022-03172-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1937: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: The GSK Bioanalytical Hub model in bioanalysis: maximizing the synergies of co-locating various platforms in support of regulated and nonregulated study end points.

Summerfield, Scott G / Tang, Huaping / Decman, Vilma / Abberley, Lee / Gunn, George / Yang, Eric

Bioanalysis

2023 Volume 15, Issue 3, Page(s) 127–132

Abstract: The term "bioanalytical" encompasses a much greater breadth of analytical deliverables than ever before. Circulating drug concentration data are complemented by experimental evidence of drug in biophase, immunogenicity, target engagement and subsequent ... ...

Abstract	The term "bioanalytical" encompasses a much greater breadth of analytical deliverables than ever before. Circulating drug concentration data are complemented by experimental evidence of drug in biophase, immunogenicity, target engagement and subsequent pathway modulation. Many bioanalytical assays bridge the traditional divide across discovery and development. Our approach is the Bioanalytical Hub model bringing together a wide breadth of bioanalytical support (GxP and non-GxP), multiple end points (pharmacokinetics, anti-drug antibodies and biomarkers) and analytical platforms (LC/MS, immunoassay, flow cytometry, genomics, immunohistochemistry) onto a common lab footprint. This maximizes instrument utilization, facilitates workforce agility and enhances data interpretation capability while reducing the number of hand-offs as assays evolve from their origins as exploratory end points to fully characterized to support primary and secondary end points.
MeSH term(s)	Mass Spectrometry ; Antibodies ; Immunoassay ; Biomarkers ; Chromatography, Liquid
Chemical Substances	Antibodies ; Biomarkers
Language	English
Publishing date	2023-03-14
Publishing country	England
Document type	Journal Article ; Review
ISSN	1757-6199
ISSN (online)	1757-6199
DOI	10.4155/bio-2022-0180
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Incurred sample reanalysis at GSK: what have we learned?

Summerfield, Scott G / Barfield, Matthew / White, Stephen A

Bioanalysis

2018 Volume 10, Issue 21, Page(s) 1755–1766

Abstract: Outcomes of incurred sample reanalysis (ISR) studies have been reviewed from a decade of internally supported bioanalysis. From over 1000 bioanalytical pharmacokinetic end points, 26 bioanalytical studies have failed against predefined ISR acceptance ... ...

Abstract	Outcomes of incurred sample reanalysis (ISR) studies have been reviewed from a decade of internally supported bioanalysis. From over 1000 bioanalytical pharmacokinetic end points, 26 bioanalytical studies have failed against predefined ISR acceptance criteria, ultimately resulting in the rejection of three partial and two full datasets (instability or preanalytic contamination). The remaining investigations highlighted methodological root causes including unexpected within-study assay variability, inappropriate assay range and sample homogeneity. However, the data variability remained acceptable for the purposes of decision-making and asset progression. Overall, ISR adds value in early development to characterize the reliability of a nascent assay and then also at the latter stages where pharmacokinetic data are pivotal to submission. However, for the intermediate development studies there is a question whether ISR adds much additional value in understanding assay performance or whether the industry is just too conservative to follow the guidance. This is where the future debate must be.
MeSH term(s)	Animals ; Chromatography, High Pressure Liquid/methods ; Chromatography, High Pressure Liquid/standards ; Drug Development/methods ; Drug Development/standards ; Humans ; Pharmacokinetics ; Quality Control ; Reproducibility of Results ; Tandem Mass Spectrometry/methods ; Tandem Mass Spectrometry/standards ; Validation Studies as Topic
Language	English
Publishing date	2018-10-16
Publishing country	England
Document type	Journal Article
ISSN	1757-6199
ISSN (online)	1757-6199
DOI	10.4155/bio-2018-0204
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: The importance of evaluating the chemical structures and strategies to avoid pitfalls in quantitative bioanalysis.

Licea-Perez, Hermes / Evans, Christopher A / Summerfield, Scott G

Bioanalysis

2018 Volume 11, Issue 2, Page(s) 85–101

Abstract: Quantitative bioanalytical data are crucial in pharmaceutical research and development, allowing project teams to make informed scientific decisions on the progression of candidate molecules to medicines. Many challenges are often encountered during the ... ...

Abstract	Quantitative bioanalytical data are crucial in pharmaceutical research and development, allowing project teams to make informed scientific decisions on the progression of candidate molecules to medicines. Many challenges are often encountered during the bioanalysis of drugs in biological matrices which require resolution in a timely manner. In this publication, guidance is provided to bioanalytical scientists on how to identify potential problems before they become an obstacle for the drug development and to share our experiences dealing some of most common problems encountered in the bioanalytical laboratory. Relevant topics in bioanalysis such as stabilization approaches for glucuronides (Acyl and N-); prodrugs (phosphate and esters), amides, amines, N-oxides; bioanalysis of light sensitive molecules, halogenated drugs and lactones are discussed in this publication.
MeSH term(s)	Animals ; Biomarkers, Pharmacological/analysis ; Chemistry, Pharmaceutical ; Drug Discovery/methods ; Humans ; Molecular Structure ; Molecular Weight ; Pharmaceutical Preparations/analysis ; Pharmaceutical Preparations/chemistry ; Prodrugs/analysis ; Prodrugs/chemistry
Chemical Substances	Biomarkers, Pharmacological ; Pharmaceutical Preparations ; Prodrugs
Language	English
Publishing date	2018-11-26
Publishing country	England
Document type	Journal Article ; Review
ISSN	1757-6199
ISSN (online)	1757-6199
DOI	10.4155/bio-2018-0211
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: In vitro, in vivo and in silico models of drug distribution into the brain.

Summerfield, Scott G / Dong, Kelly C

Journal of pharmacokinetics and pharmacodynamics

2013 Volume 40, Issue 3, Page(s) 301–314

Abstract: Achieving sufficient brain penetration to elicit efficacy in humans is one of the most challenging tasks for scientists in CNS Drug Discovery. Substantial progress has been made in the past decade in understanding the factors influencing the rate and ... ...

Abstract	Achieving sufficient brain penetration to elicit efficacy in humans is one of the most challenging tasks for scientists in CNS Drug Discovery. Substantial progress has been made in the past decade in understanding the factors influencing the rate and extent of brain distribution via a variety of in vivo, in vitro and in silico methodologies, and hence, predict their likelihood of success in man. This purpose of this review is to summarize the current approaches with a special focus on parameters related to free drug concentrations in brain which are the most pharmacologically relevant for the majority of CNS disease targets. Due to the dynamic and complex nature of this targeted organ, it is inevitable that these approaches have not been able to provide a fully comprehensive assessment of brain distribution and are expected to evolve further in the years to come.
MeSH term(s)	Animals ; Brain/metabolism ; Cell Line ; Central Nervous System Agents/blood ; Central Nervous System Agents/chemistry ; Central Nervous System Agents/pharmacokinetics ; Drug Discovery/methods ; Humans ; Models, Biological ; Structure-Activity Relationship ; Substrate Specificity ; Tissue Distribution
Chemical Substances	Central Nervous System Agents
Language	English
Publishing date	2013-02-13
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2041601-5
ISSN	1573-8744 ; 1567-567X
ISSN (online)	1573-8744
ISSN	1567-567X
DOI	10.1007/s10928-013-9303-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 980: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Examining the Uptake of Central Nervous System Drugs and Candidates across the Blood-Brain Barrier.

Summerfield, Scott G / Zhang, Yanyan / Liu, Houfu

The Journal of pharmacology and experimental therapeutics

2016 Volume 358, Issue 2, Page(s) 294–305

Abstract: Assessing the equilibration of the unbound drug concentrations across the blood-brain barrier (Kp,uu) has progressively replaced the partition coefficient based on the ratio of the total concentration in brain tissue to blood (Kp). Here, in vivo brain ... ...

Abstract	Assessing the equilibration of the unbound drug concentrations across the blood-brain barrier (Kp,uu) has progressively replaced the partition coefficient based on the ratio of the total concentration in brain tissue to blood (Kp). Here, in vivo brain distribution studies were performed on a set of central nervous system (CNS)-targeted compounds in both rats and P-glycoprotein (P-gp) genetic knockout mice. Several CNS drugs are characterized by Kp,uu values greater than unity, inferring facilitated uptake across the rodent blood-brain barrier (BBB). Examples are shown in which Kp,uu also increases above unity on knockout of P-gp, highlighting the composite nature of this parameter with respect to facilitated BBB uptake, efflux, and passive diffusion. Several molecules with high Kp,uu values share common structural elements, whereas uptake across the BBB appears more prevalent in the CNS-targeted drug set than the chemical templates being generated within the current lead optimization paradigm. Challenges for identifying high Kp,uu compounds are discussed in the context of acute versus steady-state data and cross-species differences. Evidently, there is a need for better predictive models of human brain Kp,uu.
MeSH term(s)	Animals ; Biological Transport ; Blood-Brain Barrier/metabolism ; Central Nervous System Agents/metabolism ; Drug Discovery ; Male ; Mice ; Rats
Chemical Substances	Central Nervous System Agents
Language	English
Publishing date	2016-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	3106-9
ISSN	1521-0103 ; 0022-3565
ISSN (online)	1521-0103
ISSN	0022-3565
DOI	10.1124/jpet.116.232447
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uf I Zs.40: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Toward best practices in data processing and analysis for intact biotherapeutics by MS in quantitative bioanalysis.

Kellie, John F / Kehler, Jonathan R / Karlinsey, Molly Z / Summerfield, Scott G

Bioanalysis

2017 Volume 9, Issue 23, Page(s) 1883–1893

Abstract: Aim: Typically, quantitation of biotherapeutics from biological matrices by LC-MS is based on a surrogate peptide approach to determine molecule concentration. Recent efforts have focused on quantitation of the intact protein molecules or larger mass ... ...

Abstract	Aim: Typically, quantitation of biotherapeutics from biological matrices by LC-MS is based on a surrogate peptide approach to determine molecule concentration. Recent efforts have focused on quantitation of the intact protein molecules or larger mass subunits of monoclonal antibodies. To date, there has been limited guidance for large or intact protein mass quantitation for quantitative bioanalysis. Methodology: Intact- and subunit-level analyses of biotherapeutics from biological matrices are performed at 12-25 kDa mass range with quantitation data presented. Results: Linearity, bias and other metrics are presented along with recommendations made on the viability of existing quantitation approaches. Conclusion: This communication is intended to start a discussion around intact protein data analysis and processing, recognizing that other published contributions will be required.
MeSH term(s)	Animals ; Antibodies, Monoclonal/analysis ; Antibodies, Monoclonal/blood ; Antibodies, Monoclonal/metabolism ; Chromatography, High Pressure Liquid ; Limit of Detection ; Peptides/analysis ; Rats ; Tandem Mass Spectrometry
Chemical Substances	Antibodies, Monoclonal ; Peptides
Language	English
Publishing date	2017-11-24
Publishing country	England
Document type	Journal Article
ISSN	1757-6199
ISSN (online)	1757-6199
DOI	10.4155/bio-2017-0179
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Prediction of brain:blood unbound concentration ratios in CNS drug discovery employing in silico and in vitro model systems.

Liu, Houfu / Dong, Kelly / Zhang, Wandong / Summerfield, Scott G / Terstappen, Georg C

Drug discovery today

2018 Volume 23, Issue 7, Page(s) 1357–1372

Abstract: Recent years have seen a paradigm shift away from optimizing the brain:blood concentration ratio toward the more relevant brain:blood unbound concentration ratio ( ... ...

Abstract	Recent years have seen a paradigm shift away from optimizing the brain:blood concentration ratio toward the more relevant brain:blood unbound concentration ratio (K
MeSH term(s)	Animals ; Biological Transport ; Blood-Brain Barrier/metabolism ; Capillary Permeability ; Central Nervous System Agents/administration & dosage ; Central Nervous System Agents/blood ; Central Nervous System Agents/pharmacokinetics ; Computer Simulation ; Drug Discovery/methods ; Humans ; In Vitro Techniques ; Membrane Transport Proteins/metabolism ; Models, Biological ; Tissue Distribution
Chemical Substances	Central Nervous System Agents ; Membrane Transport Proteins
Language	English
Publishing date	2018-03-13
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1324988-5
ISSN	1878-5832 ; 1359-6446
ISSN (online)	1878-5832
ISSN	1359-6446
DOI	10.1016/j.drudis.2018.03.002
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 4725: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Integrating in Silico and in Vitro Approaches To Predict Drug Accessibility to the Central Nervous System.

Zhang, Yan-Yan / Liu, Houfu / Summerfield, Scott G / Luscombe, Christopher N / Sahi, Jasminder

Molecular pharmaceutics

2016 Volume 13, Issue 5, Page(s) 1540–1550

Abstract: Estimation of uptake across the blood-brain barrier (BBB) is key to designing central nervous system (CNS) therapeutics. In silico approaches ranging from physicochemical rules to quantitative structure-activity relationship (QSAR) models are utilized to ...

Abstract	Estimation of uptake across the blood-brain barrier (BBB) is key to designing central nervous system (CNS) therapeutics. In silico approaches ranging from physicochemical rules to quantitative structure-activity relationship (QSAR) models are utilized to predict potential for CNS penetration of new chemical entities. However, there are still gaps in our knowledge of (1) the relationship between marketed human drug derived CNS-accessible chemical space and preclinical neuropharmacokinetic (neuroPK) data, (2) interpretability of the selected physicochemical descriptors, and (3) correlation of the in vitro human P-glycoprotein (P-gp) efflux ratio (ER) and in vivo rodent unbound brain-to-blood ratio (Kp,uu), as these are assays routinely used to predict clinical CNS exposure, during drug discovery. To close these gaps, we explored the CNS druglike property boundaries of 920 market oral drugs (315 CNS and 605 non-CNS) and 846 compounds (54 CNS drugs and 792 proprietary GlaxoSmithKline compounds) with available rat Kp,uu data. The exact permeability coefficient (Pexact) and P-gp ER were determined for 176 compounds from the rat Kp,uu data set. Receiver operating characteristic curves were performed to evaluate the predictive power of human P-gp ER for rat Kp,uu. Our data demonstrates that simple physicochemical rules (most acidic pKa ≥ 9.5 and TPSA < 100) in combination with P-gp ER < 1.5 provide mechanistic insights for filtering BBB permeable compounds. For comparison, six classification modeling methods were investigated using multiple sets of in silico molecular descriptors. We present a random forest model with excellent predictive power (∼0.75 overall accuracy) using the rat neuroPK data set. We also observed good concordance between the structural interpretation results and physicochemical descriptor importance from the Kp,uu classification QSAR model. In summary, we propose a novel, hybrid in silico/in vitro approach and an in silico screening model for the effective development of chemical series with the potential to achieve optimal CNS exposure.
MeSH term(s)	ATP-Binding Cassette, Sub-Family B, Member 1/metabolism ; Animals ; Biological Transport/physiology ; Blood-Brain Barrier/metabolism ; Central Nervous System/metabolism ; Central Nervous System Agents/metabolism ; Computer Simulation ; Drug Discovery/methods ; Humans ; Male ; Permeability ; Quantitative Structure-Activity Relationship ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar
Chemical Substances	ATP-Binding Cassette, Sub-Family B, Member 1 ; Central Nervous System Agents
Language	English
Publishing date	2016-05-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2138405-8
ISSN	1543-8392 ; 1543-8384
ISSN (online)	1543-8392
ISSN	1543-8384
DOI	10.1021/acs.molpharmaceut.6b00031
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6250: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito