Showing papers in "Drug Discovery Today: Technologies in 2017"

TL;DR: Two methods that produce uniform size-controlled 3D multicellular tumor spheroids that are compatible with cancer drug research and HTS are highlighted.

TL;DR: Protein–Protein Interactions and Drug Discovery Today: Technologies Vol.

TL;DR: Many proteins involved in either the ubiquitination, deubiquitination or degradation of proteins are implicated in human diseases and are currently under investigation as potential drug targets.

TL;DR: The principles behind biology-oriented synthesis and related approaches, the requirements for development of novel chemistry and how phenotypic screens are a very fruitful way to explore the bioactivity of compounds made using these approaches are described.

TL;DR: Its structural characteristics allowed the identification of reversible small-molecule inhibitors of the Keap1-Nrf2 interaction that can hopefully elucidate the therapeutic potential of Nrf2 activation.

TL;DR: The recent advancement of peptide macrocycles as promising therapeutics creates a need for novel methodologies for their efficient synthesis and (large scale) production, which will accelerate the development of future cyclic peptide therapeutics.

TL;DR: An overview of the most commonly used bioprinting approaches and how they are being used to generate complex in vitro tissues for use in toxicology and disease modeling research is provided.

TL;DR: An overview of the most recent progress in the field of SV2A PET imaging, its potential for use as a biomarker of synaptic density and the future development areas is provided.

TL;DR: To improve the physiological relevance of phenotypic assays, standardized testing of a curated set of phenotypesic pathway probes can provide a higher level of validation for phenotyping assay best practices.

TL;DR: An overview of recent developments in the field of cell penetrating peptides (CPPs) on research that aims to achieve better control over their transduction properties by means of restraining them is provided.

TL;DR: This review is meant to provide a brief overview of applied techniques for PPI elucidation, and present various case studies of PPI exploitation ranging from early discovery efforts to now-approved market drugs.

TL;DR: An overview of recent progress in resolving protein-protein and protein-chromatin interaction mechanisms of LEDGF/p75 is provided, focusing on two well-characterized domains, the PWWP domain and the integrase binding domain (IBD).

TL;DR: Clinical proof-of-concept for the theraTRACE®in vivo screening platform is exemplified by MLR-1023, a repositioned compound that has recently shown significant clinical efficacy in Type 2 diabetes patients.

TL;DR: Novel alternatives to the traditional use of reversible small molecules have emerged, including proteolytic targeting BET agents and irreversible binding inhibitors that may offer some advantage and can be used as tools to further decipher the underlying biology.

TL;DR: An overview of small-molecule library design principles as applied to phenotypic screening is provided, which increases the likelihood of identifying better quality hits, which can reduce both timelines and overall cost of the drug-discovery process.

TL;DR: This review highlights successful examples of antibody Phenotypic screens that have led to clinical drug candidates and the requirements for performing an effective antibody phenotypic screen, including antibody enrichment and target identification strategies.

TL;DR: This account highlights some of the personal experiences working with industrial partners to develop new PET radiochemistry methodologies for drug discovery and neuro-PET research studies.

TL;DR: Recent advances in the synthesis of cyclic pseudopeptides include macrocyclization through cysteine alkylation, multicomponent reactions, decarboxylative couplings, and novel stapling chemistry.

TL;DR: It is proposed that profiling of phenotypic hits and lead molecules in increasingly more complex 3D in vitro and ex vivo models at the post-translational pathway network level represents an effective strategy to both triage and progress the preclinical development of phenotypesic screening hits.

TL;DR: The scope of available carbon-11 chemistries is explored and clinical examples to highlight its value in PET studies in support of drug development are provided.

TL;DR: On-going efforts to shed light on the bioactivity of these apparently silent compounds with an emphasis on multi-parametric profiling methods are described and it is demonstrated that compounds that are dark within one institution might be found active in another, but typically show the foretold selectivity.

TL;DR: This review highlights recent progress made towards the development of glutamatergic PET imaging agents and focuses on PET imaging probes that have been labelled with either carbon-11 or fluorine-18.

TL;DR: This review focuses on mRNA display screening platforms for drug discovery and their combined use with genetic code reprogramming to identify novel macrocyclic peptides with high affinities for disease-related targets of interest.

TL;DR: Advances in neuronal screening technologies and cellular model systems that enable phenotypic screening of neuronal function as a basis for novel CNS drug discovery approaches are reviewed.

TL;DR: Jonathan Lee’s recent research emphasizes the use of complex, physiologically relevant cellular systems for target validation, biomarker discovery, lead generation, and SAR support.

TL;DR: Current approaches for imaging biological pathways with the molecular imaging technique, Positron Emission Tomography (PET), and the potential of PET imaging studies to measure the efficacy of anticancer drugs and strategies for delaying the progression of neurodegenerative disorders are described.

TL;DR: The detection of gamma rays, resulting from decay of positron emitting isotopes, allows exquisitely sensitive detection of probes radiolabeled with such isotopes that can be designed for high affinity binding to specific molecular targets and used as tools in the early development of drugs, particularly for neuropsychiatric disorders.