Showing papers in "Drug Discovery Today in 2004"

TL;DR: An analysis of literature examples reveals trends and insights that might help medicinal chemists discover the next generation of these types of compounds.

TL;DR: An overview of the latest developments in homology modeling techniques is provided and includes selected examples of successful applications of thehomology modeling technique to pharmaceutically relevant questions.

TL;DR: Results from phage display in finding peptide drug candidates are reviewed, some business benefits of developing peptides are concluded, and novel strategies have been developed for inhibiting receptor-ligand interactions are reviewed.

TL;DR: Improvements in transdermal delivery will remain incremental until there is wider acceptance of this route of administration within the pharmaceutical industry, as the trend for discovering and designing biopharmaceuticals continues.

TL;DR: The use of internalizing ligands and the targeting of intravascular tumor cells and endothelial cells of tumor blood vessels have been instrumental in demonstrating the clinical effectiveness of particulate drug carriers in animal models.

TL;DR: Recent and ongoing research seeks to address the challenge of protein therapeutic immunogenicity by elucidating the mechanisms underlying immune recognition of protein therapeutics, establishing preclinical methods for assessing Immunogenicity and developing strategies for minimizing immune responses.

TL;DR: Several emerging classes of Hsp90 inhibitors are discussed and their modes of action are discussed, including those that bind to the N-terminal ATP pocket, the C-terminus or modify its post-translational status.

TL;DR: This review presents the main findings in the field of sonophoresis, namelyTransdermal drug delivery and transdermal monitoring, with particular attention paid to proposed enhancement mechanisms and future trends in theField of cutaneous vaccination and gene delivery.

TL;DR: The need for statistical criteria in the analysis of large proteomics datasets is discussed and currently available computational tools are reviewed.

TL;DR: A novel carrier system that originates from membrane shuttling proteins such as the Drosophila homeobox protein Antennapedia, the HIV-1 transcriptional factor TAT and VP22 from HSV-1 has advantages for targeted delivery compared with standard translocation techniques.

TL;DR: Currently available resources can be split into three categories: structure-activity relationships (SAR) computational models based on compound structure, 'pattern' databases of tissue or organ response to drugs, compiled from high-throughput experiments, and 'systems biology' database of metabolic pathways, genes and regulatory networks.

TL;DR: There are three structural classes of manganese-containing catalytic antioxidants that have efficacy in several oxidative stress models of human disease that are divided based on their in vitro selectivity towards the scavenging of superoxide.

TL;DR: The activity-exposure-toxicity relationship, which can be described as "the rule of three", presents the single most difficult challenge in the design of drug candidates and their subsequent advancement to the development stage.

TL;DR: The challenges faced and the approaches taken are described to develop proteome-scale protein expression systems, highlighting the need for development of HT methods for protein isolation.

TL;DR: Structural, optical and biological assets of nanocrystals are summarized and their applications to drug discovery studies are discussed.

TL;DR: The in silico procedure of virtual screening (VS) and its relationship to the experimental procedure, HTS, is discussed, new developments in the field are summarized and perspectives on future research are offered.

TL;DR: The desolvation of the P450 active site makes a major contribution to the overall substrate-binding energy and, consequently, a good agreement with experimental information is reported based on this analysis.

TL;DR: In the past decade, several peptides that can translocate cell membranes have been identified and are capable of internalizing hydrophilic cargoes and providing a new and powerful biological tool for transporting drugs across cell membranes.

TL;DR: This review focuses on the HIF pathway as a therapeutic target because of its potential use for the treatment of ischemic disease and cancer.

TL;DR: Coupling of design of experiments with modern high-throughput automation systems has the potential to maximise the capabilities of these systems and give increased productivity for many drug discovery applications.

TL;DR: With the availability of more crystal structures for these non-target proteins, the authors should be able to predict binding in silico with a greater accuracy, thus avoiding or managing toxic side effects, therefore ultimately improving the success of drug discovery.

TL;DR: A large increase in the number of data points per day should be achieved by the introduction of automated ‘high throughput’ patch clamp machines.

TL;DR: A review of the systems currently employed shows that, whereas all systems have their own caveats, it is possible to find an appropriate system for any particular question that is asked.

TL;DR: Mice that are deficient in JNK3 are more resistant to 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine than their wild-type littermates and the inhibition of this enzyme is an attractive therapeutic target.

TL;DR: The identification of orphan nuclear receptors such as PXR and CAR represents a major step forward in understanding the pharmacological and genetic control of the expression of drug-metabolizing enzymes and the implication of this regulation in drug metabolism, drug–drug interactions, and human diseases.

TL;DR: A review of the relative merits of current and potential strategies for dealing with metabolite characterization finds that modern approaches that generate and use metabolite structural information can accelerate the drug discovery and development process.

TL;DR: A comprehensive list of drug transporters has recently become available as a result of extensive genome analysis, as well as membrane physiology and molecular biology studies, to provide clues that could lead to efficient strategies to deliver drugs and/or to optimize lead compounds.