Showing papers in "Drug Discovery Today in 2006"

TL;DR: Various endogenous factors that can positively impact the EPR effect in tumor tissues are discussed, as well as practical methods available in the clinical setting for augmenting the effect by use of exogenous agents.

TL;DR: A detailed comparison of a large number of similarity coefficients demonstrates that the well-known Tanimoto coefficient remains the method of choice for the computation of fingerprint-based similarity, despite possessing some inherent biases related to the sizes of the molecules that are being sought.

TL;DR: The concepts and prerequisites to perform virtual ligand screening are summarized here, and explanations are sought for the enduring limitations of the technology.

TL;DR: In developing oral protein delivery systems with high bioavailability, three practical approaches might be most helpful: modification of the physicochemical properties of macromolecules; addition of novel function to macromolescules; or use of improved delivery carriers.

TL;DR: Evaluation of factors related to the target antigen, antibody and patients can affect antibody elimination and evaluation of these factors will facilitate the understanding of the processes involved in antibody elimination.

TL;DR: There is increasing convergence between the number of human metabolites estimated via genomics and the number measured experimentally, and it is thus both timely, and now possible, to bring these two approaches together as an integrated whole to help understand the genesis of metabolic biomarkers, the progress of disease, and the modes of action, efficacy, off-target effects and toxicity of pharmaceutical drugs.

TL;DR: One of the most common mechanisms behind artifactual inhibition is discussed in this review: at micromolar concentrations organic molecules can aggregate to form particles in aqueous buffers, and these aggregates can sequester and thereby inhibit protein targets.

TL;DR: Several AGE inhibitors and AGE breakers have been developed in recent years, and their underlying mechanism is based on the attenuation of glycoxidation and/or oxidative stress by the sequestration of metal ions, reactive 1,2-dicarbonyl compounds, and reactive oxygen and reactive nitrogen species.

TL;DR: 'A wise use of lead discovery tactics will distinguish successful drug discovery engines,' according to the World Health Organization.

TL;DR: It appears that consensus scoring usually substantially improves virtual screening performance and also seems to improve the prediction of bound conformations and poses, contributing to better enrichments in routine lead optimization.

TL;DR: Neuroinflammation is a proinflammatory cytokine-mediated process that can be provoked by systemic tissue injury but it is most often associated with direct injury to the nervous system.

TL;DR: An analysis of octanol-water distribution coefficients is used to exemplify the consistency of estimated and calculated accuracy of the ALOGPS program (http://www.vcclab.org) to predict in-house and publicly available datasets.

TL;DR: In silico methods, employing receptor-based modeling, offer a more rational approach in the design of drugs targeting GPCRs, and various novel approaches, such as the design and potential utility of drugs that target more than one GPCR ('dual specificity' drugs).

TL;DR: Common industry practices adopted to tackle hit-to-lead challenges are summarized and how the advantages and drawbacks of different hit discovery techniques could affect the various issues hit- to-lead groups face are reviewed.

TL;DR: Novel possibilities where drugs that directly inhibit Nox activation could successfully inhibit oxidative stress are discussed, including the NADPH oxidases, xanthine oxidase, endothelial nitric oxide synthase and mitochondrial oxidases.

TL;DR: Recent progress and problems with respect to Abeta clearance mechanisms are discussed and strategies for the development of therapeutics targeting Abeta Clearance are proposed.

TL;DR: In this review, the latest developments of in vivo delivery of siRNA and the crucial issues related to this effort are addressed.

TL;DR: The binding and functionality (structure-activity relationships) of the lead structures have been optimized further and the concept of 'scaffold hopping' has been employed to expand the variability of the available chemical scaffolds and to generate patentable ligands.

TL;DR: The increasing emergence of drug resistance and the problem of mycobacterial persistence highlight the need to develop novel TB drugs that are active against drug resistant bacteria but, more importantly, kill persistent bacteria and shorten the length of treatment.

TL;DR: Two new pharmacological strategies based on the knockdown of antisense RNA transcripts by siRNA (or another RNA targeting principle) are proposed in this review and it remains to be seen whether they provide advantages in other contexts.

TL;DR: Current understanding of airborne pathogen spread in relation to the new methods of suppressing exhaled bioaerosols using safe surface-active materials, such as isotonic saline, is reviewed here.

TL;DR: Strategies for optimizing bioassays allow for adequate assessments of valuable pharmacophores for which solubility can be chemically optimized at a later date.

TL;DR: There are a variety of new neuroprotective compounds in the early stages of investigation and some could prove clinically effective, provided appropriate preclinical development guidelines are observed.

TL;DR: The role and significance of active metabolites in drug discovery and development, various experimental observations that can be used as indicators of their presence, and methods that can been used to assess their biological activities and contribution to the overall therapeutic and adverse effects of drugs are described.

TL;DR: This review highlights aspects of recent immunomics research that are related to the discovery of the T-cell immunome.

TL;DR: Differential pharmacology, function and regulation of GPCR hetero-dimers and -oligomers suggest means to selectively target GPCRs in different tissues and hint that the mechanism of function of several pharmacological agents might be different in vivo than anticipated from simple ligand-screening programmes that rely on heterologous expression of a single G PCR.

TL;DR: This work describes how to break down large numbers of screening hits and provides a comprehensive overview of the strengths and weaknesses for each structural class.

TL;DR: The recent approval of Prialt provides the ultimate target validation for N-type calcium channels, namely proof that they are key regulators of nociceptive signaling in humans.

TL;DR: Because peptide aptamers introduce perturbations that are similar to those caused by therapeutic molecules, their use identifies and/or validates therapeutic targets with a higher confidence level than is typically provided by methods that act upon protein expression levels.

TL;DR: It is interesting to note that most rationally designed multifunctional antioxidants are structurally different from their naturally occurring counterparts, therefore, nature's design strategy provides important clues as to how the design concept for multipotent antioxidants can be improved.