Discovery of PET radiopharmaceuticals at the academia-industry interface
Publication date: November 2017Source: Drug Discovery Today: Technologies, Volume 25Author(s): Vadim Bernard-Gauthier, Thomas L. Collier, Steven H. Liang, Neil VasdevProject-specific collaborations between academia and pharmaceutical partners are a growing phenomenon within molecular imaging and in particular in the positron emission tomography (PET) radiopharmaceutical community. This cultural shift can be attributed in part to decreased public funding in academia in conjunction with the increased reliance on outsourcing of chemistry, radiochemistry, pharmacology and molecular imaging studies by the pharmaceutical industr...
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
Imaging the glutamate receptor subtypes—Much achieved, and still much to do
Publication date: November 2017Source: Drug Discovery Today: Technologies, Volume 25Author(s): Stefan Gruber, Simon M. AmetameyFunctional imaging of glutamate receptors using PET imaging modality can be used to study numerous CNS disorders and also to select appropriate doses of clinically relevant glutamate-receptor-targeting candidate drugs. Great strides have been made in developing PET imaging probes for the non-invasive detection of glutamate receptors in the brain. This review highlights recent progress made towards the development of glutamatergic PET imaging agents. Focus is placed on PET imaging probes that have b...
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
Discovery and development of SV2A PET tracers: Potential for imaging synaptic density and clinical applications
Publication date: November 2017Source: Drug Discovery Today: Technologies, Volume 25Author(s): Joel Mercier, Laurent Provins, Anne ValadeImaging synaptic density in vivo has promise for numerous research and clinical applications in the diagnosis and treatment monitoring of neurodegenerative and psychiatric diseases. Recent developments in the field of PET, such as SV2A human imaging with the novel tracers UCB-A, UCB-H and UCB-J, may help in realizing this potential and bring significant benefit for the patients suffering from these diseases. This review provides an overview of the most recent progress in the field of SV2A...
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
In vivo molecular imaging tools facilitate drug discovery
Publication date: November 2017Source: Drug Discovery Today: Technologies, Volume 25Author(s): Yves P. Auberson (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
Editorial for the special issue on “constrained peptides”
Publication date: December 2017Source: Drug Discovery Today: Technologies, Volume 26Author(s): Jan H. van Maarseveen, Peter Timmerman (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
Recent advances in the synthesis of cyclic pseudopeptides
Publication date: December 2017Source: Drug Discovery Today: Technologies, Volume 26Author(s): Serge Zaretsky, Andrei K. YudinConstrained peptides pose tremendous value in drug discovery. For example, owing to their large surface areas, they offer novel ways at inhibiting protein–protein interactions. As this field has grown, it has become desirable to introduce non-peptidic functionality into these rings to enable differentiated structure activity relationships and improved pharmacokinetic properties. Recent advances in the synthesis of cyclic pseudopeptides include macrocyclization through cysteine alkylation, multicom...
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
Enzyme-catalyzed peptide cyclization
Publication date: December 2017Source: Drug Discovery Today: Technologies, Volume 26Author(s): Marcel Schmidt, Ana Toplak, Peter J.L.M. Quaedflieg, Jan H. van Maarseveen, Timo NuijensThe recent advancement of peptide macrocycles as promising therapeutics creates a need for novel methodologies for their efficient synthesis and (large scale) production. Within this context, due to the favorable properties of biocatalysts, enzyme-mediated methodologies have gained great interest. Enzymes such as sortase A, butelase 1, peptiligase and omniligase-1 represent extremely powerful and valuable enzymatic tools for peptide ligation, ...
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
Identification of nonstandard macrocyclic peptide ligands through display screening
Publication date: December 2017Source: Drug Discovery Today: Technologies, Volume 26Author(s): Rhys Dylan Taylor, Matias Rey-Carrizo, Toby Passioura, Hiroaki SugaTechniques facilitating the synthesis and screening of very high diversity nonstandard macrocyclic peptide libraries have led to such compounds receiving increasing attention as potential drug candidates. Specifically, approaches which allow the use of non-proteinogenic amino acids are proving to be particularly effective, since they expand the accessible chemical space of the starting library and thus allow the identification of compounds with structural similari...
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
Constrained cell penetrating peptides
Publication date: December 2017Source: Drug Discovery Today: Technologies, Volume 26Author(s): S.A. Bode, D.W.P.M. LöwikIn this review we provide 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 – one of the big challenges – by means of restraining them. Three different constraining strategies are presented: triggerable activation, backbone rigidification and macrocyclization. Each of these methods have their opportunities in gaining control over CPP activity and selectivity. (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
Tools to investigate the ubiquitin proteasome system
Publication date: December 2017Source: Drug Discovery Today: Technologies, Volume 26Author(s): Yves Leestemaker, Huib OvaaUbiquitin is a 76-amino acid regulatory protein involved in many important cellular processes. Ubiquitin can be attached to other proteins at either a lysine residue or to the N-terminus by the consecutive actions of E1, E2, and E3 enzymes. Ubiquitin can also be attached to itself, resulting in poly-ubiquitin chains. Ubiquitination affects substrate proteins in different ways, for example by resulting in degradation of the substrate protein by the 26S proteasome. Ubiquitination can be reversed by deubiq...
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
The multiplexed CRISPR targeting platforms
Publication date: Available online 4 February 2018Source: Drug Discovery Today: TechnologiesAuthor(s): Jian Cao, Qian Xiao, Qin YanThe discovery and engineering of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) in the past several years have revolutionized biomedical research. The CRISPR technology showed great potential to advance detection, prevention, and treatment of human diseases in the near future. Compared to previous developed genome editing approaches, such as zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), the CRISPR-based systems have numerous a...
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
Developing precision medicine using scarless genome editing of human pluripotent stem cells
Publication date: Available online 8 March 2018Source: Drug Discovery Today: TechnologiesAuthor(s): Benjamin Steyer, Evan Cory, Krishanu SahaMany avenues exist for human pluripotent stem cells (hPSCs) to impact medical care, but they may have their greatest impact on the development of precision medicine. Recent advances in genome editing and stem cell technology have enabled construction of clinically-relevant, genotype-specific “disease-in-a-dish” models. In this review, we outline the use of genome-edited hPSCs in precision disease modeling and drug screening as well as describe methodological advances in scarless g...
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
Log P as a tool in intramolecular hydrogen bond considerations
Publication date: Available online 30 March 2018Source: Drug Discovery Today: TechnologiesAuthor(s): Giulia Caron, Maura Vallaro, Giuseppe ErmondiIntramolecular hydrogen bonding (IMHB) considerations are gaining relevance in drug discovery and a molecular descriptor which can predict very early the capacity of a compound to form IMHB is needed to speed up the optimization process of drug candidates.Although log Poct is largely used for optimization purposes, in this paper we firstly use the Block Relevance (BR) analysis to theoretically show how log Poct is not a convenient choice to assess IMHB properties of candidates. T...
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
Modifying the physicochemical properties of NSAIDs for nasal and pulmonary administration
Publication date: Available online 12 April 2018Source: Drug Discovery Today: TechnologiesAuthor(s): P. Szabó-RévészThis review focuses on nasal and pulmonary delivery of NSAIDs (non-steroidal anti-inflammatory drugs) for fast-onset analgesia, for the potential prevention of Alzheimer’s disease (AD), as well as for an add-on treatment in cystic fibrosis (CF) and non-small cell lung cancer (NSCLC). I discuss how the physicochemical properties of NSAIDs can be modified with respect to the biological characteristics of the target site. Innovative technology and/or dosage forms can promote an effective therapy.Graphical a...
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
The influence and manipulation of acid/base properties in drug discovery
Publication date: Available online 26 April 2018Source: Drug Discovery Today: TechnologiesAuthor(s): David T. Manallack, Elizabeth Yuriev, David K. ChalmersThere is a growing awareness of the importance of acid/base properties in medicinal chemistry research. In many drug classes, ionisable groups are present that make critical interactions with the receptor and are essential for potency. Yet the presence of these groups may cause problems with oral bioavailability, pharmacokinetics, or toxicity. Manipulating pKa values during drug development or applying pro-drug techniques are strategies that can overcome potential defic...
Source: Drug Discovery Today: Technologies - July 6, 2018 Category: Drugs & Pharmacology Source Type: research
