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Drug Discovery Today

Vineet Jain, Keerti Jain
Visceral leishmaniasis (VL) represents the most severe form of the tropical disease, leishmaniasis. Treatment of VL is complicated because of the few clinically approved antileishmanial drugs available; emerging resistance to first-line drugs; need for a temperature-controlled 'cold' supply chain; serious toxicity concerns over drugs such as Amphotericin B; high cost of medication; and unavailability of clinically approved antileishmanial vaccines. Attacking potential molecular targets, specific to the parasite, is a vital step in the treatment of this and other infectious diseases...
September 14, 2017: Drug Discovery Today
Cláudia Azevedo, Maria Helena Macedo, Bruno Sarmento
The intracellular delivery of nanomaterials and drugs has been attracting increasing research interest, mainly because of their important effects and functions in several organelles. Targeting specific organelles can help treat or decrease the symptoms of diabetes, cancer, infectious, and autoimmune diseases. Tuning biological and chemical properties enables the creation of functionalized nanomaterials with enhanced intracellular uptake, ability to escape premature lysosome degradation, and to reach a specific target...
September 14, 2017: Drug Discovery Today
Mugdha Khaladkar, Gautier Koscielny, Samiul Hasan, Pankaj Agarwal, Ian Dunham, Deepak Rajpal, Philippe Sanseau
The recently developed Open Targets platform consolidates a wide range of comprehensive evidence associating known and potential drug targets with human diseases. We have harnessed the integrated data from this platform for novel drug repositioning opportunities. Our computational workflow systematically mines data from various evidence categories and presents potential repositioning opportunities for drugs that are marketed or being investigated in ongoing human clinical trials, based on evidence strength on target-disease pairing...
September 14, 2017: Drug Discovery Today
Peter S Kutchukian, Charlie Chang, Sean J Fox, Erica Cook, Richard Barnard, David Tellers, Huijun Wang, Dante Pertusi, Meir Glick, Robert P Sheridan, Iain Wallace, Anne Mai Wassermann
Increasing amounts of biological data are accumulating in the pharmaceutical industry and academic institutions. However, data do not equal actionable information, and guidelines for appropriate data capture, harmonization, integration, mining, and visualization need to be established to fully harness their potential. Here, we describe ongoing efforts at Merck & Co. to structure data in the area of chemogenomics. We are integrating complementary data from both internal and external data sources into one chemogenomics database (Chemical Genetic Interaction Enterprise; CHEMGENIE)...
September 14, 2017: Drug Discovery Today
Thierry Burnouf, Pierre-Alain Burnouf, Yu-Wen Wu, Er-Yuan Chuang, Long-Sheng Lu, Hadi Goubran
Circulating blood cells, and cell-derived microvesicles, are emerging as pragmatic delivery systems that can smartly complement the already existing nanotherapeutic platforms evaluated to treat or diagnose diseases. The valuable distinctive features of circulatory cells over synthetic nanocarriers encompass their biological origin which confers immune transparence, known biodegradability, high drug loading, relatively long half-life and a targeting capacity associated with their physiological surface functionality...
September 14, 2017: Drug Discovery Today
Mei Ding, Karin Kaspersson, David Murray, Catherine Bardelle
Flow cytometry is a technology providing multiparametric analysis of single cells or other suspension particles. High-throughput (HT) flow cytometry has become an attractive screening platform for drug discovery. In this review, we highlight the recent HT flow cytometry applications, and then focus on HT flow cytometry deployment at AstraZeneca (AZ). Practical considerations for successful HT flow cytometry assay development and screening are provided based on experience from four project case studies at AZ...
September 12, 2017: Drug Discovery Today
Rahul B Chavan, Nallamothu Bhargavi, Anurag Lodagekar, Nalini R Shastri
Physical characterization of solid drugs is of paramount importance because the biopharmaceutical properties and/or processing behavior can be altered. Early identification and monitoring of solid-state transformation is a crucial requirement for pharmaceutical product development. In combination with chemometrics, a nondestructive and noninvasive technique such as near infrared spectroscopy (NIR) is a powerful tool for solid-state characterization. The main focus of this review is the application of NIR for qualitative and quantitative analysis of solid forms of drugs and excipients...
September 8, 2017: Drug Discovery Today
Tim Koopmans, Reinoud Gosens
Asthma is a complex disease of the airways that develops as a consequence of both genetic and environmental factors. This interaction has highlighted genes important in early life, particularly those that control lung development, such as the Wingless/Integrase-1 (WNT) signalling pathway. Although aberrant WNT signalling is involved with an array of human conditions, it has received little attention within the context of asthma. Yet it is highly relevant, driving events involved with inflammation, airway remodelling, and airway hyper-responsiveness (AHR)...
September 7, 2017: Drug Discovery Today
Gianpiero Calabrese, Anis Daou, Eugen Barbu, John Tsibouklis
Boron neutron capture therapy (BNCT) is a promising targeted chemoradiotherapeutic technique for the management of invasive brain tumors, such as glioblastoma multiforme (GBM). A prerequisite for effective BNCT is the selective targeting of tumour cells with (10)B-rich therapeutic moieties. To this end, polyhedral boranes, especially carboranes, have received considerable attention because they combine a high boron content with relative low toxicity and metabolic inertness. Here, we review progress in the molecular design of recently investigated carborane derivatives in light of the widely accepted performance requirements for effective BNCT...
September 5, 2017: Drug Discovery Today
Lu Zhang, Jianjun Tan, Dan Han, Hao Zhu
Machine intelligence, which is normally presented as artificial intelligence, refers to the intelligence exhibited by computers. In the history of rational drug discovery, various machine intelligence approaches have been applied to guide traditional experiments, which are expensive and time-consuming. Over the past several decades, machine-learning tools, such as quantitative structure-activity relationship (QSAR) modeling, were developed that can identify potential biological active molecules from millions of candidate compounds quickly and cheaply...
September 4, 2017: Drug Discovery Today
Hong Zhao, Ruihua Ding, Xin Zhao, Yiwei Li, Liangliang Qu, Hao Pei, Lara Yildirimer, Zhengwei Wu, Weixia Zhang
Here, we discuss the biomedical applications of graphene-based nanomaterials (GBNs). We examine graphene and its various derivatives, including graphene, graphene oxides (GOs), reduced graphene oxides (rGOs), graphene quantum dots (GQDs), and graphene composites, and discuss their unique properties related to their biomedical applications. We also summarize the detailed biomedical applications of GBNs, including drug and/or gene delivery, bioimaging, and tissue engineering. We also highlight the toxicity of these nanomaterials...
September 1, 2017: Drug Discovery Today
Melek Simsek, Berrie Meijer, Adriaan A van Bodegraven, Nanne K H de Boer, Chris J J Mulder
Identifying new indications for existing drugs creates new therapeutic options while bypassing much of the costs and time involved with bringing a new drug to market. The rediscovery of a generic drug, however, is a challenging pursuit because there is no formal regulatory approach and a lack of economic interest by pharmaceutical companies. This played a part in the re-registration of thioguanine as a rescue drug for the treatment of patients with inflammatory bowel disease in The Netherlands. In this article, we aim to underline the importance of drug rediscovery, the difficulties of this procedure in Europe and we attempt to suggest conceivable solutions...
September 1, 2017: Drug Discovery Today
Frederic D C Martin, Amanda Benjamin, Ruth MacLean, David M Hollinshead, Claire Landqvist
In 2012, AstraZeneca entered into a strategic relationship with Charles River Laboratories whereby preclinical safety packages comprising safety pharmacology, toxicology, formulation analysis, in vivo ADME, bioanalysis and pharmacokinetics studies are outsourced. New processes were put in place to ensure seamless workflows with the aim of accelerating the delivery of new medicines to patients. Here, we describe in more detail the AstraZeneca preclinical safety outsourcing model and the way in which a collaborative tool has helped to translate the processes in AstraZeneca and Charles River Laboratories into simpler integrated workflows that are efficient and visible across the two companies...
August 26, 2017: Drug Discovery Today
Soumyadip Das, Bharathi Suresh, Hyongbum Henry Kim, Suresh Ramakrishna
The Ran-binding protein microtubule-organizing center (RanBPM) is a highly conserved nucleocytoplasmic protein involved in a variety of intracellular signaling pathways that control diverse cellular functions. RanBPM interacts with proteins that are linked to various diseases, including Alzheimer's disease (AD), schizophrenia (SCZ), and cancer. In this article, we define the characteristics of the scaffolding protein RanBPM and focus on its interaction partners in diverse physiological disorders, such as neurological diseases, fertility disorders, and cancer...
August 26, 2017: Drug Discovery Today
Pawan K Mishra, Harshita Mishra, Adam Ekielski, Sushama Talegaonkar, Bhuvaneshwar Vaidya
Zinc oxide (ZnO) nanoparticles (NPs) are a promising platform for use in biomedical research, especially given their anticancer and antimicrobial activities. These activities are associated with the ability of ZnO NPs to generate reactive oxygen species (ROS) and induce apoptosis. In addition, ZnO NPs have been successfully exploited as drug carriers for loading and transporting drugs to target sites, thereby reducing unwanted toxicity and off-target effects, and resulting in amplified synergistic effects. Here, we discuss the synthesis and biomedical applications of ZnO NPs...
August 25, 2017: Drug Discovery Today
Rakesh K Tekade, Xiankai Sun
Tumor cells are known for their propensity to proliferate uncontrollably and generate multitudes of metastatic masses at the advanced stages of cancer. During this progression, tumor cells switch their energy source from mitochondrial oxidative phosphorylation to a glucose-dependent glycolytic pathway, despite the availability of oxygen. Consequently, tumor cells increase their metabolic rates as well as glucose uptake to maintain their proliferation. This atypical metabolic phenomenon is known as the Warburg effect, which has been recognized as a hallmark of cancer and serves as a promising target for diagnosis and therapy of cancer...
August 24, 2017: Drug Discovery Today
Joseph C Somody, Stephen S MacKinnon, Andreas Windemuth
Structure-based computational drug discovery efforts have traditionally focused on the structure of a single, well-known drug target. Important applications, such as target deconvolution and the analysis of polypharmacology, require proteome-scale molecular docking and have been inaccessible to structure-based in silico approaches. One important reason for this inaccessibility was that the structure of most proteins was not known. Lately, this 'structure gap' has been closing rapidly, and proteome-scale molecular docking seems within reach...
August 23, 2017: Drug Discovery Today
Guorui Jin, Xin Zhao, Feng Xu
No abstract text is available yet for this article.
August 10, 2017: Drug Discovery Today
Rhys D O Jones, Marie Cooke, James Hinchliffe, Justin Morley, Simon T Barry
In vivo models have been crucial for developing our understanding of key processes associated with human disease and developing novel therapeutics. These in vivo studies are becoming increasingly complex, requiring long-term efficacy data and additional supportive datasets such as pharmacokinetic profiles and analysis of multiple biomarkers of pharmacodynamic response and efficacy. Moreover, a new agent will be investigated in many different models and often in combination with other drugs. Despite advances across the industry integrating and analysing complex datasets, management of in vivo data remains an ongoing challenge across the industry...
August 9, 2017: Drug Discovery Today
Madhu M Kanchi, Muthu K Shanmugam, Grishma Rane, Gautam Sethi, Alan P Kumar
Vitamin E family members: tocotrienols and tocopherols are widely known for their health benefits. Decades of research on tocotrienols have shown they have diverse biological activities such as antioxidant, anti-inflammatory, anticancer, neuroprotective and skin protection benefits, as well as improved cognition, bone health, longevity and reduction of cholesterol levels in plasma. Tocotrienols also modulate several intracellular molecular targets and, most importantly, have been shown to improve lipid profiles, reduce total cholesterol and reduce the volume of white matter lesions in human clinical trials...
August 5, 2017: Drug Discovery Today
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