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https://www.readbyqxmd.com/read/28642701/the-market-of-biopharmaceutical-medicines-a-snapshot-of-a-diverse-industrial-landscape
#1
Evelien Moorkens, Nicolas Meuwissen, Isabelle Huys, Paul Declerck, Arnold G Vulto, Steven Simoens
Background: Biopharmaceutical medicines represent a growing share of the global pharmaceutical market, and with many of these biopharmaceutical products facing loss of exclusivity rights, also biosimilars may now enter the biopharmaceutical market. Objectives: This study aims to identify and document which investment and development strategies are adopted by industrial players in the global biopharmaceutical market. Methods: A descriptive analysis was undertaken of the investment and development strategies of the top 25 pharmaceutical companies according to 2015 worldwide prescription drug sales...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28642145/new-and-improved-a-review-of-novel-antibiotics-for-gram-positive-bacteria
#2
REVIEW
Mohamed Abbas, Mical Paul, Angela Huttner
BACKGROUND: The number of antibiotics in the pipeline targeting Gram-positive pathogens has increased in recent years. AIMS: This narrative review aims to provide a summary of existing evidence on efficacy, microbiologic spectrum, and safety of novel systemic antibiotics that have either recently been licenced or completed phase III trials, and possess activity predominantly against Gram-positive organisms. SOURCES: A review of the published literature via the MEDLINE database was performed...
June 19, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28641198/combined-computational-experimental-approach-to-predict-blood-brain-barrier-bbb-permeation-based-on-green-salting-out-thin-layer-chromatography-supported-by-simple-molecular-descriptors
#3
Krzesimir Ciura, Mariusz Belka, Piotr Kawczak, Tomasz Bączek, Michał J Markuszewski, Joanna Nowakowska
The objective of this paper is to build QSRR/QSAR model for predicting the blood-brain barrier (BBB) permeability. The obtained models are based on salting-out thin layer chromatography (SOTLC) constants and calculated molecular descriptors. Among chromatographic methods SOTLC was chosen, since the mobile phases are free of organic solvent. As consequences, there are less toxic, and have lower environmental impact compared to classical reserved phases liquid chromatography (RPLC). During the study three stationary phase silica gel, cellulose plates and neutral aluminum oxide were examined...
June 3, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28638238/a-computational-methodology-to-overcome-the-challenges-associated-with-the-search-for-specific-enzyme-targets-to-develop-drugs-against-leishmania-major
#4
Larissa Catharina, Carlyle Ribeiro Lima, Alexander Franca, Ana Carolina Ramos Guimarães, Marcelo Alves-Ferreira, Pierre Tuffery, Philippe Derreumaux, Nicolas Carels
We present an approach for detecting enzymes that are specific of Leishmania major compared with Homo sapiens and provide targets that may assist research in drug development. This approach is based on traditional techniques of sequence homology comparison by similarity search and Markov modeling; it integrates the characterization of enzymatic functionality, secondary and tertiary protein structures, protein domain architecture, and metabolic environment. From 67 enzymes represented by 42 enzymatic activities classified by AnEnPi (Analogous Enzymes Pipeline) as specific for L major compared with H sapiens, only 40 (23 Enzyme Commission [EC] numbers) could actually be considered as strictly specific of L major and 27 enzymes (19 EC numbers) were disregarded for having ambiguous homologies or analogies with H sapiens...
2017: Bioinformatics and Biology Insights
https://www.readbyqxmd.com/read/28636311/insights-into-integrated-lead-generation-and-target-identification-in-malaria-and-tuberculosis-drug-discovery
#5
John Okombo, Kelly Chibale
New, safe and effective drugs are urgently needed to treat and control malaria and tuberculosis, which affect millions of people annually. However, financial return on investment in the poor settings where these diseases are mostly prevalent is very minimal to support market-driven drug discovery and development. Moreover, the imminent loss of therapeutic lifespan of existing therapies due to evolution and spread of drug resistance further compounds the urgency to identify novel effective drugs. However, the advent of new public-private partnerships focused on tropical diseases and the recent release of large data sets by pharmaceutical companies on antimalarial and antituberculosis compounds derived from phenotypic whole cell high throughput screening have spurred renewed interest and opened new frontiers in malaria and tuberculosis drug discovery...
June 21, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28635674/exploring-wound-healing-genomic-machinery-with-a-network-based-approach
#6
Francesca Vitali, Simone Marini, Martina Balli, Hanne Grosemans, Maurilio Sampaolesi, Yves A Lussier, Maria Gabriella Cusella De Angelis, Riccardo Bellazzi
The molecular mechanisms underlying tissue regeneration and wound healing are still poorly understood despite their importance. In this paper we develop a bioinformatics approach, combining biology and network theory to drive experiments for better understanding the genetic underpinnings of wound healing mechanisms and for selecting potential drug targets. We start by selecting literature-relevant genes in murine wound healing, and inferring from them a Protein-Protein Interaction (PPI) network. Then, we analyze the network to rank wound healing-related genes according to their topological properties...
June 21, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28635653/virtual-screening-against-phosphoglycerate-kinase-1-in-quest-of-novel-apoptosis-inhibitors
#7
Jie Xia, Bo Feng, Qianhang Shao, Yuhe Yuan, Xiang Simon Wang, Naihong Chen, Song Wu
Inhibition of apoptosis is a potential therapy to treat human diseases such as neurodegenerative disorders (e.g., Parkinson's disease), stroke, and sepsis. Due to the lack of druggable targets, it remains a major challenge to discover apoptosis inhibitors. The recent repositioning of a marketed drug (i.e., terazosin) as an anti-apoptotic agent uncovered a novel target (i.e., human phosphoglycerate kinase 1 (hPgk1)). In this study, we developed a virtual screening (VS) pipeline based on the X-ray structure of Pgk1/terazosin complex and applied it to a screening campaign for potential anti-apoptotic agents...
June 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28632997/epidemiology-of-obesity-and-pharmacologic-treatment-options
#8
Vignesh Shettar, Sarang Patel, Srividya Kidambi
Prevalence of obesity and its related morbidity have increased to alarming levels in adults and children in the United States and globally. Weight loss results in improvement of much of the obesity-related morbidity. Lifestyle changes such as dietary modifications, increased physical activity, and behavioral therapy form the crux of weight management. However, many individuals need additional assistance (pharmacologic or surgical) to initiate or sustain weight loss. Pharmacologic therapy consists of a number of agents that work by decreasing appetite, gastric emptying, or nutrient absorption or by increasing satiety...
June 1, 2017: Nutrition in Clinical Practice
https://www.readbyqxmd.com/read/28628201/designing-drug-response-experiments-and-quantifying-their-results
#9
Marc Hafner, Mario Niepel, Kartik Subramanian, Peter K Sorger
We developed a Python package to help in performing drug-response experiments at medium and high throughput and evaluating sensitivity metrics from the resulting data. In this article, we describe the steps involved in (1) generating files necessary for treating cells with the HP D300 drug dispenser, by pin transfer or by manual pipetting; (2) merging the data generated by high-throughput slide scanners, such as the Perkin Elmer Operetta, with treatment annotations; and (3) analyzing the results to obtain data normalized to untreated controls and sensitivity metrics such as IC50 or GR50 ...
June 19, 2017: Current Protocols in Chemical Biology
https://www.readbyqxmd.com/read/28625727/incomplete-loading-of-sls-and-fassif-micelles-within-the-diffusion-layers-of-dispersed-drug-particles-during-dissolution
#10
Kendra Galipeau, Michael Socki, Adam Socia, Paul A Harmon
Poorly water soluble drug candidates have been common in developmental pipelines over the last several decades. This has fueled considerable research around understanding how bile salt and model micelles can improve drug particle dissolution rates and human drug exposure levels. However, in the pharmaceutical context only a single mechanism of how micelles load solute has been assumed, that being the direct loading mechanism put forth by Cussler(1) 40 years ago. In this model micelles load at the particle surface and will be loaded to their equilibrium loading values...
June 15, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28617888/position-paper-on-treatment-of-hepatitis-c-in-romania-2017-part-one
#11
Liana Gheorghe, Ioan Sporea, Speranţa Iacob, Roxana Şirli, Anca Trifan, Daniela Dobru, Mircea Diculescu, Carol Stanciu, Oliviu Pascu, Monica Acalovschi, Ciprian Brisc, Cristina Cijevschi, Cristian Gheorghe, Zeno Spârchez, Ion Rogoveanu, Dan Dumitrascu
BACKGROUND AND AIMS: Hepatitis C Virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania the mean prevalence is about 3%. New treatments became available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country. METHODOLOGY: A group of recognized experts was created who screened the available literature and the major available guidelines...
June 2017: Journal of Gastrointestinal and Liver Diseases: JGLD
https://www.readbyqxmd.com/read/28617137/drugs-currently-under-investigation-for-the-treatment-of-invasive-candidiasis
#12
Matthew W McCarthy, Thomas J Walsh
The widespread implementation of immunosuppressants, immunomodulators, hematopoietic stem cell transplantation and solid organ transplantation in clinical practice has led to an expanding population of patients who are at risk for invasive candidiasis, which is the most common form of fungal disease among hospitalized patients in the developed world. The emergence of drug-resistant Candida spp. has added to the morbidity associated with invasive candidiasis and novel therapeutic strategies are urgently needed...
June 15, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28615526/identifying-prognostic-signature-in-ovarian-cancer-using-dirgenerank
#13
Jian-Yong Wang, Ling-Ling Chen, Xiong-Hui Zhou
Identifying the prognostic genes in cancer is essential not only for the treatment of cancer patients, but also for drug discovery. However, it's still a big challenge to select the prognostic genes that can distinguish the risk of cancer patients across various data sets because of tumor heterogeneity. In this situation, the selected genes whose expression levels are statistically related to prognostic risks may be passengers. In this paper, based on gene expression data and prognostic data of ovarian cancer patients, we used conditional mutual information to construct gene dependency network in which the nodes (genes) with more out-degrees have more chances to be the modulators of cancer prognosis...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28604120/current-and-developing-synthetic-pharmacotherapy-for-treating-relapsed-refractory-multiple-myeloma
#14
Klaus Podar, Martin Pecherstorfer
The introduction of novel agents has significantly improved multiple myeloma (MM) patient outcome during the last two decades. MM received the most drug approvals for any one malignancy during this time period, both in the United States as well as in Europe. Areas covered: Proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies are prototype drug classes, which target both specific MM cell functions, as well as the tumor supportive bone marrow microenvironment, and represent current cornerstones of MM therapy...
June 12, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28603140/mining-the-genome-for-therapeutic-targets
#15
Jose C Florez
Current pharmacological options for type 2 diabetes do not cure the disease. Despite the availability of multiple drug classes that modulate glycemia effectively and minimize long-term complications, these agents do not reverse pathogenesis, and in practice they are not selected to correct the molecular profile specific to the patient. Pharmaceutical companies find drug development programs increasingly costly and burdensome, and many promising compounds fail before launch to market. Human genetics can help advance the therapeutic enterprise...
June 11, 2017: Diabetes
https://www.readbyqxmd.com/read/28598490/development-of-a-zebrafish-sepsis-model-for-high-throughput-drug-discovery
#16
Anju Mary Philip, Youdong Wang, Antonio Mauro, Suzan El-Rass, John C Marshall, Warren L Lee, Arthur S Slutsky, Claudia C dosSantos, Xiao-Yan Wen
Sepsis is a leading cause of death worldwide. Current treatment modalities remain largely supportive. Intervention strategies focused on inhibiting specific mediators of the inflammatory host response have been largely unsuccessful, a consequence of an inadequate understanding of the complexity and heterogeneity of the innate immune response. Moreover, the conventional drug development pipeline is time consuming and expensive and the low success rates associated with cell-based screens underline the need for whole organism screening strategies, especially for complex pathological processes...
June 7, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28596718/mass-spectrometry-based-metabolomics-for-in-vitro-systems-pharmacology-pitfalls-challenges-and-computational-solutions
#17
Stephanie Herman, Payam Emami Khoonsari, Obaid Aftab, Shibu Krishnan, Emil Strömbom, Rolf Larsson, Ulf Hammerling, Ola Spjuth, Kim Kultima, Mats Gustafsson
INTRODUCTION: Mass spectrometry based metabolomics has become a promising complement and alternative to transcriptomics and proteomics in many fields including in vitro systems pharmacology. Despite several merits, metabolomics based on liquid chromatography mass spectrometry (LC-MS) is a developing area that is yet attached to several pitfalls and challenges. To reach a level of high reliability and robustness, these issues need to be tackled by implementation of refined experimental and computational protocols...
2017: Metabolomics: Official Journal of the Metabolomic Society
https://www.readbyqxmd.com/read/28594404/precision-medicine-for-hepatocelluar-carcinoma-using-molecular-pattern-diagnostics-results-from-a-preclinical-pilot-study
#18
Rahul Agarwal, Yuan Cao, Klaus Hoffmeier, Nicolas Krezdorn, Lukas Jost, Alejandro Rodriguez Meisel, Ruth Jüngling, Francesco Dituri, Serena Mancarella, Björn Rotter, Peter Winter, Gianluigi Giannelli
The aim of this study was to design a road map for personalizing cancer therapy in hepatocellular carcinoma (HCC) by using molecular pattern diagnostics. As an exploratory study, we investigated molecular patterns of tissues of two tumors from individual HCC patients, which in previous experiments had shown contrasting reactions to the phase 2 transforming growth factor beta receptor 1 inhibitor galunisertib. Cancer-driving molecular patterns encompass - inter alias - altered transcription profiles and somatic mutations in coding regions differentiating tumors from their respective peritumoral tissues and from each other...
June 8, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28592399/dacomitinib-beats-gefitinib-for-egfr-nsclc
#19
(no author information available yet)
The irreversible EGFR inhibitor dacomitinib reduced the chance of lung cancer progression compared with an older, first-generation EGFR inhibitor, gefitinib, in a phase III trial. As reported at the 2017 American Society of Clinical Oncology Annual Meeting, the experimental drug also increased toxicity, which could limit its use, especially with a safer, more effective third-generation EGFR inhibitor not far behind in the development pipeline.
June 7, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28569147/serendipitous-discovery-of-light-induced-in-situ-formation-of-an-azo-bridged-dimeric-sulfonated-naphthol-as-a-potent-ptp1b-inhibitor
#20
Robert D Bongard, Michael Lepley, Khushabu Thakur, Marat R Talipov, Jaladhi Nayak, Rachel A Jones Lipinski, Chris Bohl, Noreena Sweeney, Ramani Ramchandran, Rajendra Rathore, Daniel S Sem
BACKGROUND: Protein tyrosine phosphatases (PTPs) like dual specificity phosphatase 5 (DUSP5) and protein tyrosine phosphatase 1B (PTP1B) are drug targets for diseases that include cancer, diabetes, and vascular disorders such as hemangiomas. The PTPs are also known to be notoriously difficult targets for designing inihibitors that become viable drug leads. Therefore, the pipeline for approved drugs in this class is minimal. Furthermore, drug screening for targets like PTPs often produce false positive and false negative results...
May 31, 2017: BMC Biochemistry
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