Cyclodextrin Inclusion of Medicinal Compounds for Enhancement of their Physicochemical and Biopharmaceutical Properties

2019 ◽  
Vol 19 (25) ◽  
pp. 2357-2370 ◽  
Author(s):  
Mino R. Caira
Keyword(s):  
Drug Discovery ◽  
Inclusion Complexation ◽  
Structural Diversity ◽  
Attrition Rate ◽  
Cyclodextrin Inclusion ◽  
Biopharmaceutical Properties ◽  
Fine Tune ◽  
Early Drug ◽  
Selection Of

Owing to their wide structural diversity and unique complexing properties, cyclodextrins (CDs) find manifold applications in drug discovery and development. The focus of this mini-review is on their uses as ‘enabling excipients’ both in the context of early drug discovery and in subsequent optimisation of drug performance. Features highlighted here include descriptions of the structures of CDs, synthetic derivatisation to fine-tune their properties, the nature of inclusion complexation of drugs within the CD cavity, methodology for the study of free and complexed hosts in the solid state and in solution, the inherent pharmacological activity of several CDs and its utility, novel CD-based drug delivery systems, and the role of CDs in drug discovery and optimisation. Illustrative examples are generally based on research reported during the last two decades. Application of CDs to the optimisation of the performance of established drugs is commonplace, but there are many opportunities for the intervention of CDs during the early stages of drug discovery, which could guide the selection of suitable candidates for development, thereby contributing to reducing the attrition rate of new molecular entities.

scholarly journals Inhibition of Microglia Activation as a Phenotypic Assay in Early Drug Discovery

2013 ◽  
Vol 19 (1) ◽  
pp. 17-31 ◽  
Author(s):  
Mariana Figuera-Losada ◽  
Camilo Rojas ◽  
Barbara S. Slusher
Keyword(s):  
Drug Discovery ◽  
Nuclear Factor Κb ◽  
Microglia Activation ◽  
Biologically Active ◽  
Therapeutic Drugs ◽  
Mitogen Activated Protein ◽  
Disproportionate Number ◽  
Early Drug

Complex biological processes such as inflammation, cell death, migration, proliferation, and the release of biologically active molecules can be used as outcomes in phenotypic assays during early stages of drug discovery. Although target-based approaches have been widely used over the past decades, a disproportionate number of first-in-class drugs have been identified using phenotypic screening. This review details phenotypic assays based on inhibition of microglial activation and their utility in primary and secondary screening, target validation, and pathway elucidation. The role of microglia, both in normal as well as in pathological conditions such as chronic neurodegenerative diseases, is reviewed. Methodologies to assess microglia activation in vitro are discussed in detail, and classes of therapeutic drugs known to decrease the proinflammatory and cytotoxic responses of activated microglia are appraised, including inhibitors of glutaminase, cystine/glutamate antiporter, nuclear factor κB, and mitogen-activated protein kinases.

scholarly journals The Central Role of PDR1 in the Foundation of Yeast Drug Resistance

2006 ◽  
Vol 282 (7) ◽  
pp. 5063-5074 ◽  
Author(s):  
Vivienne Fardeau ◽  
Gaëlle Lelandais ◽  
Andrew Oldfield ◽  
Hélène Salin ◽  
Sophie Lemoine ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Genetic Determinants ◽  
Term Selection ◽  
Basal Expression ◽  
Drug Dependent ◽  
Dna Binding Properties ◽  
Early Drug ◽  
Selection Of

The widespread pleiotropic drug resistance (PDR) phenomenon is well described as the long term selection of genetic variants expressing constitutively high levels of membrane transporters involved in drug efflux. However, the transcriptional cascades leading to the PDR phenotype in wild-type cells are largely unknown, and the first steps of this phenomenon are poorly understood. We investigated the transcriptional mechanisms underlying the establishment of an efficient PDR response in budding yeast. We show that within a few minutes of drug sensing yeast elicits an effective PDR response, involving tens of PDR genes. This early PDR response (ePDR) is highly dependent on the Pdr1p transcription factor, which is also one of the major genetic determinants of long term PDR acquisition. The activity of Pdr1p in early drug response is not drug-specific, as two chemically unrelated drugs, benomyl and fluphenazine, elicit identical, Pdr1p-dependent, ePDR patterns. Our data also demonstrate that Pdr1p is an original stress response factor, the DNA binding properties of which do not depend on the presence of drugs. Thus, Pdr1p is a promoter-resident regulator involved in both basal expression and rapid drug-dependent induction of PDR genes.

scholarly journals The Role of Drug Metabolism in Drug Discovery: A Case Study in the Selection of an Oxytocin Receptor Antagonist for Development

1995 ◽  
Vol 23 (2) ◽  
pp. 124-130 ◽  
Author(s):  
Shuet-Ling L. Chiu ◽  
A. Thompson ◽  
Stella H. Vincent ◽  
Raul F. Alvaro ◽  
Su-Er W. Huskey ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Drug Metabolism ◽  
Receptor Antagonist ◽  
Oxytocin Receptor ◽  
Selection Of

scholarly journals Commentary: Why Pharmaceutical Scientists in Early Drug Discovery Are Critical for Influencing the Design and Selection of Optimal Drug Candidates

2017 ◽  
Vol 19 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Margaret S. Landis ◽  
Shobha Bhattachar ◽  
Mehran Yazdanian ◽  
John Morrison
Keyword(s):  
Drug Discovery ◽  
Drug Candidates ◽  
Optimal Drug ◽  
Early Drug ◽  
Selection Of

scholarly journals Die Rolle von Eiche, Totholz und Efeubeeren bei der Habitatwahl des Mittelspechts

2016 ◽  
Vol 167 (1) ◽  
pp. 21-28
Author(s):  
Lisa Spühler ◽  
Bertil O. Krüsi ◽  
Gilberto Pasinelli
Keyword(s):  
Forest Ecosystems ◽  
Structural Diversity ◽  
Positive Development ◽  
Dead Trees ◽  
Habitat Factors ◽  
Standing Dead ◽  
Middle Spotted Woodpecker ◽  
Selection Of ◽  
The Eu

The role of oak, deadwood and ivy for habitat selection of the middle spotted woodpecker Due to their habitat needs, woodpeckers are generally considered to be excellent indicators of forest habitat quality and biodiversity. In the EU and in Switzerland, the middle spotted woodpecker acts as a flagship species for nature conservation in forests. After several decades of decline in the Canton of Zurich, the population of the indicator species more than doubled between 2002 and 2012. The reasons for this positive development are so far unknown. It is hypothesized that an increased availability of ivy berries, sometimes eaten by the middle spotted woodpecker, may have contributed to the population growth. Based on the woodpecker monitoring 2012 in the Canton of Zurich, in 2013 the availability of trees with ivy berries at sites with and without presence of the middle spotted woodpecker was examined in eight forests. At the same time we also studied the availability of oaks and standing dead trees, two habitat factors well known to be important for the middle spotted woodpecker. Results revealed significantly shorter distances to large oaks and a tendency towards shorter distances to dead trees at points with middle spotted woodpecker presence than at points without. The distance to trees with ivy berries, on the other hand, was the same at presence and absence points. Occurrence probability of the middle spotted woodpecker was best explained by the distances to the closest large oak and to the closest standing dead tree, respectively. The importance of ivy contributing to the structural diversity in forest ecosystems and providing food and refuge to many species is widely recognized. Therefore, ivy should not be eliminated and oaks and dead trees should be continued to be fostered.

Faculty selection of textbooks: Key variables and the role of teaching experience

2010 ◽  
Author(s):  
Aja Taitano ◽  
Bradley Smith ◽  
Cade Hulbert ◽  
Kristin Batten ◽  
Lalania Woodstrom ◽  
...  
Keyword(s):  
Teaching Experience ◽  
Key Variables ◽  
Faculty Selection ◽  
Selection Of

Posttransplant CMV infection and the role of immunosuppression (Sponsor: Novartis Pharma GmbH, Nürnberg)

2016 ◽  
Vol 04 (01) ◽  
pp. 4-10
Keyword(s):  
Lower Incidence ◽  
Paradigm Shift ◽  
Mtor Inhibitor ◽  
De Novo ◽  
Expert Panel ◽  
Risk Of Infection ◽  
Cmv Infection ◽  
Expert Meeting ◽  
Selection Of

AbstractImmunosuppression permits graft survival after transplantation and consequently a longer and better life. On the other hand, it increases the risk of infection, for instance with cytomegalovirus (CMV). However, the various available immunosuppressive therapies differ in this regard. One of the first clinical trials using de novo everolimus after kidney transplantation [1] already revealed a considerably lower incidence of CMV infection in the everolimus arms than in the mycophenolate mofetil (MMF) arm. This result was repeatedly confirmed in later studies [2–4]. Everolimus is now considered a substance with antiviral properties. This article is based on the expert meeting “Posttransplant CMV infection and the role of immunosuppression”. The expert panel called for a paradigm shift: In a CMV prevention strategy the targeted selection of the immunosuppressive therapy is also a key element. For patients with elevated risk of CMV, mTOR inhibitor-based immunosuppression is advantageous as it is associated with a significantly lower incidence of CMV events.

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