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Drug Discovery Today

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https://www.readbyqxmd.com/read/28336175/the-academic-industrial-complex-navigating-the-translational-and-cultural-divide
#1
REVIEW
Stephen Freedman, Kevin Mullane
In general, the fruits of academic discoveries can only be realized through joint efforts with industry. However, the poor reproducibility of much academic research has damaged credibility and jeopardized translational efforts that could benefit patients. Meanwhile, journals are rife with articles bemoaning the limited productivity and increasing costs of the biopharmaceutical industry and its resultant predilection for mergers and reorganizations while decreasing internal research efforts. The ensuing disarray and uncertainty has created tremendous opportunities for academia and industry to form even closer ties, and to embrace new operational and financial models to their joint benefit...
March 20, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28288783/factors-related-to-drug-approvals-predictors-of-outcome
#2
REVIEW
Lawrence Liberti, Alasdair Breckenridge, Jarno Hoekman, Neil McAuslane, Pieter Stolk, Hubert Leufkens
There is growing interest in characterising factors associated with positive regulatory outcomes for drug marketing authorisations. We assessed empirical studies published over the past 15 years seeking to identify predictive factors. Factors were classified to one of four 'factor clusters': evidentiary support; product or indication characteristics; company experience or strategy; social and regulatory factors. We observed a heterogeneous mix of technical factors (e.g., study designs, clinical evidence of efficacy) and less studied social factors (e...
March 10, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28288782/exosomes-a-new-horizon-in-lung-cancer
#3
REVIEW
Irene Vanni, Angela Alama, Francesco Grossi, Maria Giovanna Dal Bello, Simona Coco
Circulating exosomes are the major mediators of cell-cell communication. They have been found in various body fluids of healthy individuals and patients with malignancies as cargos of several molecules including miRNAs. Several studies have underlined the role of exosome miRNAs in different tumor types, including lung cancer, suggesting their potential use as biomarkers and therapeutic agents. An overview of the biology and function of exosomes and exosome miRNAs as indicators of diagnosis and treatment response in lung cancer is presented...
March 10, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28284830/technological-advances-and-proteomic-applications-in-drug-discovery-and-target-deconvolution-identification-of-the-pleiotropic-effects-of-statins
#4
REVIEW
Cristina Banfi, Roberta Baetta, Erica Gianazza, Elena Tremoli
Proteomic-based techniques provide a powerful tool for identifying the full spectrum of protein targets of a drug, elucidating its mechanism(s) of action, and identifying biomarkers of its efficacy and safety. Herein, we outline the technological advancements in the field, and illustrate the contribution of proteomics to the definition of the pharmacological profile of statins, which represent the cornerstone of the prevention and treatment of cardiovascular diseases (CVDs). Statins act by inhibiting 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, thus reducing cholesterol biosynthesis and consequently enhancing the clearance of low-density lipoproteins from the blood; however, HMG-CoA reductase inhibition can result in a multitude of additional effects beyond lipid lowering, known as 'pleiotropic effects'...
March 8, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28279788/containment-challenges-in-hpapi-manufacture-for-adc-generation
#5
REVIEW
Elizabeth Dunny, Imelda O'Connor, Jonathan Bones
Antibody-drug conjugates (ADCs) are emerging as an impactful class of therapeutics for the treatment of cancer because of their ability to harness the specificity of an antibody and the cytotoxic potential of the payload to target and destroy cancer cells. However, the potent nature of the cytotoxic payload creates associated manufacturing challenges for active pharmaceutical ingredient (API) manufacturers, because huge investment in containment technology is required to ensure the protection of operators and the environment...
March 6, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28274840/systemic-qsar-and-phenotypic-virtual-screening-chasing-butterflies-in-drug-discovery
#6
REVIEW
Maykel Cruz-Monteagudo, Stephan Schürer, Eduardo Tejera, Yunierkis Pérez-Castillo, José L Medina-Franco, Aminael Sánchez-Rodríguez, Fernanda Borges
Current advances in systems biology suggest a new change of paradigm reinforcing the holistic nature of the drug discovery process. According to the principles of systems biology, a simple drug perturbing a network of targets can trigger complex reactions. Therefore, it is possible to connect initial events with final outcomes and consequently prioritize those events, leading to a desired effect. Here, we introduce a new concept, 'Systemic Chemogenomics/Quantitative Structure-Activity Relationship (QSAR)'. To elaborate on the concept, relevant information surrounding it is addressed...
March 6, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28219742/the-use-of-nanoscaffolds-and-dendrimers-in-tissue-engineering
#7
REVIEW
Bapi Gorain, Muktika Tekade, Prashant Kesharwani, Arun K Iyer, Kiran Kalia, Rakesh Kumar Tekade
To avoid tissue rejection during organ transplantation, research has focused on the use of tissue engineering to regenerate required tissues or organs for patients. The biomedical applications of hyperbranched, multivalent, structurally uniform, biocompatible dendrimers in tissue engineering include the mimicking of natural extracellular matrices (ECMs) in the 3D microenvironment. Dendrimers are unimolecular architects that can incorporate a variety of biological and/or chemical substances in a 3D architecture to actively support the scaffold microenvironment during cell growth...
February 20, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28212948/the-importance-of-the-glycosylation-of-antimicrobial-peptides-natural-and-synthetic-approaches
#8
REVIEW
Natalia G Bednarska, Brendan W Wren, Sam J Willcocks
Glycosylation is one of the most prevalent post-translational modifications of a protein, with a defining impact on its structure and function. Many of the proteins involved in the innate or adaptive immune response, including cytokines, chemokines, and antimicrobial peptides (AMPs), are glycosylated, contributing to their myriad activities. The current availability of synthetic coupling and glycoengineering technology makes it possible to customise the most beneficial glycan modifications for improved AMP stability, microbicidal potency, pathogen specificity, tissue or cell targeting, and immunomodulation...
February 14, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28189800/is-the-european-regulatory-framework-sufficient-to-assure-the-safety-of-citizens-using-health-products-containing-nanomaterials
#9
REVIEW
Umberto M Musazzi, Valentina Marini, Antonella Casiraghi, Paola Minghetti
The growing application of nanomaterials in healthcare products (i.e., cosmetics, medical devices, and medicinal products) has encouraged the upgrade of the regulatory framework within the European Community to better control their use and manage the risk of negative effects on human health and environment. Unfortunately, despite the efforts of European Authorities, the current legislation is still stratified and several criticisms remain because of the lack of well-established scientific knowledge on nanomaterials...
February 9, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28188894/emerging-rna-editing-biomarkers-will-foster-drug-development
#10
REVIEW
Siem van der Laan, Nicolas Salvetat, Dinah Weissmann, Franck Molina
Unanticipated adverse drug reactions (ADRs) on the central nervous system are a major cause of clinical attrition and market withdrawal. Current practices for their prospective assessment still lean on extensive analysis of rodent behaviour despite their highly controversial predictive value. Human-derived in vitro models that objectively quantify mechanism-related biomarkers can greatly contribute to better ADR prediction at early developmental stages. Adenosine-to-inosine RNA editing constitutes a physiological cellular process that translates environmental cues by regulating protein function at the synaptic level in health and disease...
February 7, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28179145/bringing-new-dimensions-to-drug-discovery-screening-impact-of-cellular-stimulation-technologies
#11
REVIEW
Elena Molokanova, Mark Mercola, Alex Savchenko
The current mandate for the drug discovery industry is to develop more efficient drugs faster while reducing the costs associated with their development. Incorporation of cell stimulation technologies during screening assays is expected to revolutionize the discovery of novel drugs as well as safety pharmacology. In this review, we highlight 'classical' and emerging cell stimulation technologies that provide the ability to evaluate the effects of drug candidates on cells in different functional states to assess clinically relevant phenotypes...
February 4, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28163155/next-generation-sequencing-big-data-meets-high-performance-computing
#12
REVIEW
Bertil Schmidt, Andreas Hildebrandt
The progress of next-generation sequencing has a major impact on medical and genomic research. This high-throughput technology can now produce billions of short DNA or RNA fragments in excess of a few terabytes of data in a single run. This leads to massive datasets used by a wide range of applications including personalized cancer treatment and precision medicine. In addition to the hugely increased throughput, the cost of using high-throughput technologies has been dramatically decreasing. A low sequencing cost of around US$1000 per genome has now rendered large population-scale projects feasible...
February 2, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28159625/safety-of-antisense-oligonucleotide-and-sirna-based-therapeutics
#13
REVIEW
Xuan Chi, Philip Gatti, Thomas Papoian
Oligonucleotide-based therapy is an active area of drug development designed to treat a variety of gene-specific diseases. Two of the more promising platforms are the antisense oligonucleotides (ASOs) and short interfering RNAs (siRNAs), both of which are often directed against similar targets. In light of recent reports on clinical trials of severe thrombocytopenia with two different ASO drugs and increased peripheral neuropathy with an siRNA drug, we compared and contrasted the specific safety characteristics of these two classes of oligonucleotide therapeutic...
January 31, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28153670/designing-a-bio-inspired-biomimetic-in-vitro-system-for-the-optimization-of-ex-vivo-studies-of-pancreatic-cancer
#14
REVIEW
Stella Totti, Spyros I Vernardis, Lisiane Meira, Pedro A Pérez-Mancera, Eithne Costello, William Greenhalf, Daniel Palmer, John Neoptolemos, Athanasios Mantalaris, Eirini G Velliou
Pancreatic cancer is one of the most aggressive and lethal human malignancies. Drug therapies and radiotherapy are used for treatment as adjuvants to surgery, but outcomes remain disappointing. Advances in tissue engineering suggest that 3D cultures can reflect the in vivo tumor microenvironment and can guarantee a physiological distribution of oxygen, nutrients, and drugs, making them promising low-cost tools for therapy development. Here, we review crucial structural and environmental elements that should be considered for an accurate design of an ex vivo platform for studies of pancreatic cancer...
January 30, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28137645/how-can-nanoparticles-contribute-to-antituberculosis-therapy
#15
REVIEW
Joana Costa-Gouveia, José A Aínsa, Priscille Brodin, Ainhoa Lucía
Therapeutic approaches using nanoparticles are being successfully used in foods and in several fields of medicine, including infectious diseases. Regarding tuberculosis (TB) treatment, nanoparticles can be a useful strategy for two distinct applications: (i) for their intrinsic antimycobacterial activity; (ii) as vehicles for known antitubercular drugs to allow reduction of dose- and drug-associated side-effects and administration via user-friendly administration routes such as pulmonary or oral ones. Promising results were obtained in vitro and in animal Mycobacterium tuberculosis models and need now to be translated into clinical drug candidates...
January 27, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28137644/measuring-the-effectiveness-and-impact-of-an-open-innovation-platform
#16
REVIEW
Glenn P Carroll, Sanjay Srivastava, Adam S Volini, Marta M Piñeiro-Núñez, Tatiana Vetman
Today, most pharmaceutical companies complement their traditional R&D models with some variation on the Open Innovation (OI) approach in an effort to better access global scientific talent, ideas and hypotheses. Traditional performance indicators that measure economic returns from R&D through commercialization are often not applicable to the practical assessment of these OI approaches, particularly within the context of early drug discovery. This leaves OI programs focused on early R&D without a standard assessment framework from which to evaluate overall performance...
January 27, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28130117/can-pharmaceutical-co-crystals-provide-an-opportunity-to-modify-the-biological-properties-of-drugs
#17
Alessandro Dalpiaz, Barbara Pavan, Valeria Ferretti
Poorly soluble and/or permeable molecules jeopardize the discovery and development of innovative medicines. Pharmaceutical co-crystals, formed by an active pharmaceutical substance (API) and a co-crystal former, can show enhanced dissolution and permeation values compared with those of the parent crystalline pure phases. It is currently assumed that co-crystallization with pharmaceutical excipients does not affect the pharmacological activity of an API or, indeed, might even improve physical properties such as solubility and permeability...
January 24, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28115264/models-for-drug-absorption-from-the-small-intestine-where-are-we-and-where-are-we-going
#18
REVIEW
Pierre-André Billat, Emilie Roger, Sébastien Faure, Frédéric Lagarce
The small intestine is a complex organ with movements, flora, mucus and flows. Despite this, the most widely used absorption models consider the organ a cylindrical monoepithelial tube. This review presents the recent evolution of models to take into consideration the complex nature of gut physiology. The most commonly encountered issues are ethical (in vivo models) and differences in drug transport as a result of a modified expression of drug transporters or metabolic enzymes compared with human (in vitro and in vivo models)...
January 20, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28111331/assessing-molecular-scaffolds-for-cns-drug-discovery
#19
Joan Mayol-Llinàs, Adam Nelson, William Farnaby, Andrew Ayscough
There is a need for high-quality screening collections that maximise hit rate and minimise the time taken in lead optimisation to derive a candidate drug. Identifying and accessing molecules that meet these criteria is a challenge. Within central nervous system (CNS)-focused drug discovery, this challenge is heightened by the requirement for lead compounds to cross the blood-brain barrier. Herein, we demonstrate use of a multiparameter optimisation tool to prioritise the synthesis of molecular scaffolds that, when subsequently decorated, yield screening compounds with experimentally determined properties that align with CNS lead generation needs...
January 20, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28111332/therapeutic-interventions-for-aging-the-case-of-cellular-senescence
#20
REVIEW
Abel Soto-Gamez, Marco Demaria
Organismal aging is a multifactorial process characterized by the onset of degenerative conditions and cancer. One of the key drivers of aging is cellular senescence, a state of irreversible growth arrest induced by many pro-tumorigenic stresses. Senescent cells accumulate late in life and at sites of age-related pathologies, where they contribute to disease onset and progression through complex cell and non-cell autonomous effects. Here, we summarize the mechanisms by which cellular senescence can promote aging, and we offer an extensive description of current potential pharmacological interventions for senescent cells, highlighting limitations and suggesting alternatives...
January 19, 2017: Drug Discovery Today
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