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Pipeline drugs

Tal Lorberbaum, Kevin J Sampson, Jeremy B Chang, Vivek Iyer, Raymond L Woosley, Robert S Kass, Nicholas P Tatonetti
BACKGROUND: QT interval-prolonging drug-drug interactions (QT-DDIs) may increase the risk of life-threatening arrhythmia. Despite guidelines for testing from regulatory agencies, these interactions are usually discovered after drugs are marketed and may go undiscovered for years. OBJECTIVES: Using a combination of adverse event reports, electronic health records (EHR), and laboratory experiments, the goal of this study was to develop a data-driven pipeline for discovering QT-DDIs...
October 18, 2016: Journal of the American College of Cardiology
Pedram Ramin, Andreas Libonati Brock, Fabio Polesel, Ana Causanilles, Erik Emke, Pim de Voogt, Benedek Gy Plosz
Sewer pipelines, although primarily designed for sewage transport, can also be considered as bioreactors. In-sewer processes may lead to significant variations of chemical loadings from source release points to the treatment plant influent. In this study, we assessed in-sewer utilization of growth substrates (primary metabolic processes) and transformation of illicit drug biomarkers (secondary metabolic processes) by suspended biomass. Sixteen drug biomarkers were targeted, including mephedrone, methadone, cocaine, heroin, codeine and tetrahydrocannabinol (THC) and their major human metabolites...
October 14, 2016: Environmental Science & Technology
Aastha Gupta, Sandeep Juneja, Marco Vitoria, Vincent Habiyambere, Boniface Dongmo Nguimfack, Meg Doherty, Daniel Low-Beer
With anti-retroviral treatment (ART) scale-up set to continue over the next few years it is of key importance that manufacturers and planners in low- and middle-income countries (LMICs) hardest hit by the HIV/AIDS pandemic are able to anticipate and respond to future changes to treatment regimens, generics pipeline and demand, in order to secure continued access to all ARV medicines required. We did a forecast analysis, using secondary WHO and UNAIDS data sources, to estimate the number of people living with HIV (PLHIV) and the market share and demand for a range of new and existing ARV drugs in LMICs up to 2025...
2016: PloS One
Joshua I Siner, Benjamin J Samelson-Jones, Julie M Crudele, Robert A French, Benjamin J Lee, Shanzhen Zhou, Elizabeth Merricks, Robin Raymer, Timothy C Nichols, Rodney M Camire, Valder R Arruda
Processing by the proprotein convertase furin is believed to be critical for the biological activity of multiple proteins involved in hemostasis, including coagulation factor VIII (FVIII). This belief prompted the retention of the furin recognition motif (amino acids 1645-1648) in the design of B-domain-deleted FVIII (FVIII-BDD) products in current clinical use and in the drug development pipeline, as well as in experimental FVIII gene therapy strategies. Here, we report that processing by furin is in fact deleterious to FVIII-BDD secretion and procoagulant activity...
October 6, 2016: JCI Insight
Harrison Liu, Steven Chen, Kevin Huang, Jeffrey Kim, Han Mo, Raffael Iovine, Julie Gendre, Pauline Pascal, Qiang Li, Yaping Sun, Zhiqiang Dong, Michelle Arkin, Su Guo, Bo Huang
Drug discovery in whole-organisms such as zebrafish is a promising approach for identifying biologically-relevant lead compounds. However, high content imaging of zebrafish at cellular resolution is challenging due to the difficulty in orienting larvae en masse such that the cell type of interest is in clear view. We report the development of the multi-pose imaging method, which uses 96-well round bottom plates combined with a standard liquid handler to repose the larvae within each well multiple times, such that an image in a specific orientation can be acquired...
2016: PloS One
Héloïse Ragelle, Fabienne Danhier, Véronique Préat, Robert Langer, Daniel G Anderson
Nanomedicine has emerged as a major field of academic research with direct impact on human health. While a first generation of products has been successfully commercialized and has significantly contributed to enhance patient's life, recent advances in material design and the emergence of new therapeutics are contributing to the development of more sophisticated systems. As the field matures, it is important to comprehend the challenges related to nanoparticle commercial development for a more efficient and predictable path to the clinic...
October 12, 2016: Expert Opinion on Drug Delivery
Ahmad Abu Turab Naqvi, Farah Anjum, Faez Iqbal Khan, Asimul Islam, Faizan Ahmad, Md Imtaiyaz Hassan
Helicobacter pylori is a Gram-negative bacteria that is responsible for gastritis in human. Its spiral flagellated body helps in locomotion and colonization in the host environment. It is capable of living in the highly acidic environment of the stomach with the help of acid adaptive genes. The genome of H. pylori 26695 strain contains 1,555 coding genes that encode 1,445 proteins. Out of these, 340 proteins are characterized as hypothetical proteins (HP). This study involves extensive analysis of the HPs using an established pipeline which comprises various bioinformatics tools and databases to find out probable functions of the HPs and identification of virulence factors...
September 2016: Genomics & Informatics
Vaishali Gaikwad, Tejash Gohel, Shrijeet Panickar, Vijay Chincholkar, Santosh Mangalkar
INTRODUCTION: Staphylococcus is one of the most common causes of nosocomial infection, especially pneumonia, surgical site infections, blood stream infections, and continues to be a major cause of community-acquired infections. The emergence of penicillin resistance followed by the development and spread of strains resistant to the semisynthetic penicillins such as methicillin, oxacillin and nafcillin, macrolides, tetracycline, and aminoglycosides has made the treatment of staphylococcal infection a global challenge...
October 2016: Indian Journal of Pathology & Microbiology
Ranjeet Prasad Dash, R Jayachandra Babu, Nuggehally R Srinivas
1. Several SGLT-2 inhibitors are in clinical use for the management of type 2 diabetes. The objectives of the current review were: a) to provide a comparative pharmacokinetics including absorption, distribution, metabolism and excretory (ADME) profiles of three SGLT2 inhibitors namely: sergliflozin, remogliflozin and ertugliflozin; b) to provide some perspectives on possible developmental issues. 2. Based on the t1/2 values observed in humans, the rank order of the three SGLT-2 inhibitors were ertugliflozin (16 h) > remogliflozin (2-4 h) >sergliflozin (1-1...
October 10, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
John Christian Givhan Spainhour, Peng Qiu
BACKGROUND: With the advent of large scale biological data collection for various diseases, data analysis pipelines and workflows need to be established to build frameworks for integrative analysis. Here the authors present a pipeline for identifying disease specific gene-drug interactions using CNV (Copy Number Variation) and clinical data from the TCGA (The Cancer Genome Atlas) project. Two cancer types were selected for analysis, LGG (Brain lower grade glioma) and GBM (Glioblastoma multiforme), due to the possible progression from LGG to GBM in some cases...
October 6, 2016: BMC Bioinformatics
Craig R MacNair, Jonathan M Stokes, Shawn French, Cullen L Myers, Kali R Iyer, Eric D Brown
The rapid spread of antibiotic resistance has created a pressing need for the development of novel drug screening platforms. Herein, we report on the use of cell-based kinetic dose response curves for small molecule characterization in antibiotic discovery efforts. Kinetically monitoring bacterial growth at sub-inhibitory concentrations of antimicrobial small molecules generates unique dose response profiles. We show that clustering of profiles by growth characteristics can classify antibiotics by mechanism of action...
September 22, 2016: Bioorganic & Medicinal Chemistry
Supriyo Bhattacharya, Romelia Salomon-Ferrer, Sangbae Lee, Nagarajan Vaidehi
GPCRs are transmembrane receptors involved in diverse biological functions. Despite the diversity in their amino acid sequences, class A GPCRs exhibit a conserved structural topology and possibly common mechanism of receptor activation. To understand how this high sequence diversity translates to a conserved functional mechanism, we have compared the dynamic behavior of eight class A GPCRs comprising of six biogenic amine receptors, and the adenosine A2A and a peptide receptor protease activated receptor 1...
October 6, 2016: Journal of Chemical Theory and Computation
Fabiano A Tofoli, Maximiliano Dasso, Mariana Morato-Marques, Kelly Nunes, Lucas Assis Pereira, Giselle Siqueira da Silva, Simone A S Fonseca, Roberta Montero Costas, Hadassa Campos Santos, Alexandre da Costa Pereira, Paulo A Lotufo, Isabela M Bensenor, Diogo Meyer, Lygia Veiga Pereira
Human pluripotent stem cells (hPSCs) may significantly improve drug development pipeline, serving as an in vitro system for the identification of novel leads, and for testing drug toxicity. Furthermore, these cells may be used to address the issue of differential drug response, a phenomenon greatly influenced by genetic factors. This application depends on the availability of hPSC lines from populations with diverse ancestries. So far, it has been reported that most lines of hPSCs derived worldwide are of European or East Asian ancestries...
October 6, 2016: Scientific Reports
(no author information available yet)
Estimates of future growth in the oncology market, a predicted increase of 11% per year in sales, and the need to expand drug-development pipelines to sustain profits have been driving up the value of corporate mergers, such as Pfizer's purchase of Medivation for $14 billion.
September 30, 2016: Cancer Discovery
Sergio Cantoreggi
Sergio Cantoreggi speaks to Henry Ireland, Commissioning Editor: Sergio Cantoreggi, PhD, is the Chief Scientific Officer and Global Head of Research and Development of the Helsinn Group, a mid-sized pharmaceutical company headquartered in Lugano, Switzerland, and focused on providing cancer supportive care solutions to oncology patients worldwide. Dr Cantoreggi has overall responsibility for all R&D activities of the Helsinn Group and has contributed to six major regulatory approvals of cancer supportive care agents in the USA, Europe and Japan...
October 3, 2016: Future Oncology
Matthew H Ung, Frederick S Varn, Chao Cheng
Leukemia is a collection of highly heterogeneous cancers that arise from neoplastic transformation and clonal expansion of immature hematopoietic cells. Post-treatment recurrence is high, especially among elderly patients, thus necessitating more effective treatment modalities. Development of novel anti-leukemic compounds relies heavily on traditional in vitro screens which require extensive resources and time. Therefore, integration of in silico screens prior to experimental validation can improve the efficiency of pre-clinical drug development...
October 11, 2016: Expert Opinion on Drug Discovery
Dalia Buffery
No abstract text is available yet for this article.
June 2016: American Health & Drug Benefits
Molly Campa, Alan Menter
INTRODUCTION: Interleukin-17 has recently been identified as a key player in the pathogenesis of psoriasis. As such, several drugs targeting IL-17 are in various stages of clinical development. AREAS COVERED: In this review, the authors describe several emerging therapies and drug candidates targeting IL-17. The authors detail many biologic injectable drug candidates as well as numerous potential oral and topical small molecule drug candidates. EXPERT OPINION: Approval of IL-17 inhibitors has significantly improved the treatment options for psoriasis patients...
September 30, 2016: Expert Opinion on Investigational Drugs
Adam S Brown, Chirag J Patel
OBJECTIVE: Drug repositioning is a promising methodology for reducing the cost and duration of the drug discovery pipeline. We sought to develop a computational repositioning method leveraging annotations in the literature, such as Medical Subject Heading (MeSH) terms. METHODS: We developed software to determine significantly co-occurring drug-MeSH term pairs and a method to estimate pair-wise literature-derived distances between drugs. RESULTS: We found that literature-based drug-drug similarities predicted the number of shared indications across drug-drug pairs...
September 27, 2016: Journal of the American Medical Informatics Association: JAMIA
V Erdeljic Turk, I Simic, R Likic, K Makar-Ausperger, M Radacic-Aumiler, I Cegec, D Juricic Nahal, I Kraljickovic
No abstract text is available yet for this article.
October 6, 2016: Clinical Therapeutics
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