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https://www.readbyqxmd.com/read/27916649/new-horizons-for-cystic-fibrosis-treatment
#1
REVIEW
Isabelle Fajac, Kris De Boeck
Cystic fibrosis is an inherited multi-system disease associated with chronic lung infection, malabsorption, salt loss syndromes, male infertility and leading to numerous comorbidities. The landscape in cystic fibrosis care has changed markedly with currently more adult patients than children in many countries. Over 2000 different mutations in theCFTRgene have been reported and the majority are extremely rare. Understanding howCFTRmutations translate to disturbed synthesis or function of the CFTR protein has opened the way to 'personalized' treatments to correct the basic defect...
December 1, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27913670/screening-for-chemical-modulators-for-lrrk2
#2
REVIEW
Heather Mortiboys
After the discovery of leucine-rich repeat kinase 2 (LRRK2) as a risk factor for sporadic Parkinson's disease (PD) and mutations in LRRK2 as a cause of some forms of familial PD, there has been substantial interest in finding chemical modulators of LRRK2 function. Most of the pathogenic mutations in LRRK2 are within the enzymatic cores of the protein; therefore, many screens have focused on finding chemical modulators of this enzymatic activity. There are alternative screening approaches that could be taken to investigate compounds that modulate LRRK2 cellular functions...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27902994/targeted-immunomodulatory-therapy-an-overview
#3
Ashley L Lefebvre, Laura McAuliffe
Monoclonal antibodies and other biologic response modifiers have allowed for targeted drug therapy in managing various autoimmune diseases. A number of immune pathways have been exploited in the development of targeted immunomodulatory therapies, including cytokine-directed therapies such as tumor necrosis factor-alpha and interleukins, integrins, B-cells, and co-stimulation modulators. With new targeted therapies in the pipeline, more options are becoming available for treatment of autoimmune diseases. [Full article available at http://rimed...
December 1, 2016: Rhode Island Medical Journal
https://www.readbyqxmd.com/read/27901159/a-portable-and-reconfigurable-multi-organ-platform-for-drug-development-with-onboard-microfluidic-flow-control
#4
J R Coppeta, M J Mescher, B C Isenberg, A J Spencer, E S Kim, A R Lever, T J Mulhern, R Prantil-Baun, J C Comolli, J T Borenstein
The drug development pipeline is severely limited by a lack of reliable tools for prediction of human clinical safety and efficacy profiles for compounds at the pre-clinical stage. Here we present the design and implementation of a platform technology comprising multiple human cell-based tissue models in a portable and reconfigurable format that supports individual organ function and crosstalk for periods of up to several weeks. Organ perfusion and crosstalk are enabled by a precision flow control technology based on electromagnetic actuators embedded in an arrayed format on a microfluidic platform...
November 30, 2016: Lab on a Chip
https://www.readbyqxmd.com/read/27896754/application-of-multiplex-biomarker-approaches-to-accelerate-drug-discovery-and-development
#5
Hassan Rahmoune, Paul C Guest
Multiplex biomarker tests are becoming an essential part of the drug development process. This chapter explores the role of biomarker-based tests as effective tools in improving preclinical research and clinical development, and the challenges that this presents. The potential of incorporating biomarkers in the clinical pipeline to improve decision making, accelerate drug development, improve translation, and reduce development costs is discussed. This chapter also discusses the latest biomarker technologies in use to make this possible and details the next steps that must undertaken to keep driving this process forwards...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27893735/computational-discovery-of-putative-leads-for-drug-repositioning-through-drug-target-interaction-prediction
#6
Edgar D Coelho, Joel P Arrais, José Luís Oliveira
De novo experimental drug discovery is an expensive and time-consuming task. It requires the identification of drug-target interactions (DTIs) towards targets of biological interest, either to inhibit or enhance a specific molecular function. Dedicated computational models for protein simulation and DTI prediction are crucial for speed and to reduce the costs associated with DTI identification. In this paper we present a computational pipeline that enables the discovery of putative leads for drug repositioning that can be applied to any microbial proteome, as long as the interactome of interest is at least partially known...
November 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27890821/molecular-dynamics-driven-drug-discovery-leaping-forward-with-confidence
#7
REVIEW
Aravindhan Ganesan, Michelle L Coote, Khaled Barakat
Given the significant time and financial costs of developing a commercial drug, it remains important to constantly reform the drug discovery pipeline with novel technologies that can narrow the candidates down to the most promising lead compounds for clinical testing. The past decade has witnessed tremendous growth in computational capabilities that enable in silico approaches to expedite drug discovery processes. Molecular dynamics (MD) has become a particularly important tool in drug design and discovery...
November 24, 2016: Drug Discovery Today
https://www.readbyqxmd.com/read/27890820/recent-developments-in-natural-product-based-drug-discovery-for-tuberculosis
#8
REVIEW
Maryline Dong, Bernhard Pfeiffer, Karl-Heinz Altmann
Natural products (NPs) have been at the origin of several established drugs against tuberculosis (TB). Although the current clinical TB pipeline does not feature any candidates derived from new NP scaffolds, numerous novel NP or NP analogs have been discovered in the recent past with promising activity against Mycobacterium tuberculosis (Mtb) This includes newly discovered structures as well as known NP classes that had not been previously recognized to be active against Mtb. These compounds could help to replenish the dry clinical TB pipeline and, thus, contribute to improvements in the treatment of a devastating disease...
November 24, 2016: Drug Discovery Today
https://www.readbyqxmd.com/read/27884742/antifungals
#9
REVIEW
Sonia Campoy, José L Adrio
The need for new antifungal agents is undeniable. Current therapeutics choices for the treatment of invasive fungal infections are limited to three classes of drugs. Most used antifungals agents are not completely effective due to the development of resistance, host toxicity and undesirable side effects that limit their use in medical practice. Invasive fungal infections have significantly increased over the last decades and the mortality rates remain unacceptably high. More threatening, new resistance patterns have been observed including simultaneous resistance to different antifungal classes...
November 21, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27881429/a-review-of-validation-strategies-for-computational-drug-repositioning
#10
Adam S Brown, Chirag J Patel
Repositioning of previously approved drugs is a promising methodology because it reduces the cost and duration of the drug development pipeline and reduces the likelihood of unforeseen adverse events. Computational repositioning is especially appealing because of the ability to rapidly screen candidates in silico and to reduce the number of possible repositioning candidates. What is unclear, however, is how useful such methods are in producing clinically efficacious repositioning hypotheses. Furthermore, there is no agreement in the field over the proper way to perform validation of in silico predictions, and in fact no systematic review of repositioning validation methodologies...
November 22, 2016: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/27870245/the-art-of-compiling-protein-binding-site-ensembles
#11
Stefan Bietz, Rainer Fährrolfes, Matthias Rarey
Structure-based drug design starts with the collection, preparation, and initial analysis of protein structures. With more than 115,000 structures publically available in the Protein Data Bank (PDB), fully automated processes reliably performing these important preprocessing steps are needed. Several tools are available for these tasks, however, most of them do not address the special needs of scientists interested in protein-ligand interactions. In this paper, we summarize our research activities towards an automated processing pipeline from raw PDB data towards ready-to-use protein binding site ensembles...
December 2016: Molecular Informatics
https://www.readbyqxmd.com/read/27867045/minvar-a-rapid-and-versatile-tool-for-hiv-1-drug-resistance-genotyping-by-deep-sequencing
#12
Michael Huber, Karin J Metzner, Fabienne D Geissberger, Cyril Shah, Christine Leemann, Thomas Klimkait, Jürg Böni, Alexandra Trkola, Osvaldo Zagordi
Genotypic monitoring of drug-resistance mutations (DRMs) in HIV-1 infected individuals is strongly recommended to guide selection of the initial antiretroviral therapy (ART) and changes of drug regimens. Traditionally, mutations conferring drug resistance are detected by population sequencing of the reverse transcribed viral RNA encoding the HIV-1 enzymes target by ART, followed by manual analysis and interpretation of Sanger sequencing traces. This process is labor intensive, relies on subjective interpretation from the operator, and offers limited sensitivity as only mutations above 20% frequency can be reliably detected...
November 17, 2016: Journal of Virological Methods
https://www.readbyqxmd.com/read/27865740/sm-p80-based-schistosomiasis-vaccine-preparation-for-human-clinical-trials
#13
REVIEW
Afzal A Siddiqui, Sabrina Z Siddiqui
Mass antiparasitic drug administration programs and other control strategies have made important contributions in reducing the global prevalence of helminths. Schistosomiasis, however, continues to spread to new geographic areas. The advent of a viable vaccine and its deployment, coupled with existing control efforts, is expected to make significant headway towards sustained schistosomiasis control. In 2016, Science ranked the schistosomiasis vaccine as one of the top 10 vaccines that needs to be urgently developed...
November 16, 2016: Trends in Parasitology
https://www.readbyqxmd.com/read/27865394/recent-developments-in-genomics-bioinformatics-and-drug-discovery-to-combat-emerging-drug-resistant-tuberculosis
#14
REVIEW
Soumya Swaminathan, Jagadish Chandrabose Sundaramurthi, Alangudi Natarajan Palaniappan, Sujatha Narayanan
Emergence of drug-resistant tuberculosis (DR-TB) is a big challenge in TB control. The delay in diagnosis of DR-TB leads to its increased transmission, and therefore prevalence. Recent developments in genomics have enabled whole genome sequencing (WGS) of Mycobacterium tuberculosis (M. tuberculosis) from 3-day-old liquid culture and directly from uncultured sputa, while new bioinformatics tools facilitate to determine DR mutations rapidly from the resulting sequences. The present drug discovery and development pipeline is filled with candidate drugs which have shown efficacy against DR-TB...
December 2016: Tuberculosis
https://www.readbyqxmd.com/read/27859674/an-integrative-drug-repurposing-pipeline-switching-viral-drugs-to-breast-cancer
#15
K Ramanathan, Kanika Verma, Velin Marita Sequeira, B Lokapriya Nandan, V Shanthi
The growing incidence rate of breast cancer, coupled with cellular chemotherapeutic resistance, has made this disease one of the most prevalent cancers among women worldwide. Despite the recent efforts to understand the underlying cause of the resistance due to mutation, there are no feasible tactics to overcome this bottleneck. This issue could be addressed by the concept of polypharmacology - disguising drugs present in the pharmacopeia for novel purposes (drug repurposing). Of note, we have proposed a multi-modal computational drug repositioning stratagem to predict drugs possessing anti-proliferative effect...
November 17, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27859453/past-present-and-future-of-antibacterial-economics-increasing-bacterial-resistance-limited-antibiotic-pipeline-and-societal-implications
#16
Katherine H Luepke, Katie J Suda, Helen Boucher, Rene L Russo, Michael W Bonney, Timothy D Hunt, John F Mohr
Growing antimicrobial resistance and a dwindling antibiotic pipeline has resulted in an emerging postantibiotic era, as patients are now dying from bacterial infections that were once treatable. The fast-paced "Golden Age" of antibiotic development that started in the 1940s has lost momentum, as from the 1980s to the early 2000s, there was a 90% decline in approval of new antibiotics as well as discovery of few new novel classes. Many companies have shifted away from development due to scientific, regulatory, and economic hurdles that proved antibiotic development to be less attractive compared with more lucrative therapeutic areas...
November 12, 2016: Pharmacotherapy
https://www.readbyqxmd.com/read/27856684/psychedelics-in-the-treatment-of-unipolar-mood-disorders-a-systematic-review
#17
REVIEW
James Jh Rucker, Luke A Jelen, Sarah Flynn, Kyle D Frowde, Allan H Young
Unipolar mood disorders, including major depressive disorder and persistent depressive disorder (dysthymia), confer high rates of disability and mortality and a very high socioeconomic burden. Current treatment is suboptimal in most cases and there is little of note in the pharmaceutical development pipeline. The psychedelic drugs, including lysergic acid diethylamide and psilocybin, were used extensively in the treatment of mood disorders, and other psychiatric conditions, before their prohibition in the late 1960s...
December 2016: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/27845727/ligand-fishing-a-remarkable-strategy-for-discovering-bioactive-compounds-from-complex-mixture-of-natural-products
#18
REVIEW
Rongjie Zhuo, Hao Liu, Ningning Liu, Yi Wang
Identification of active compounds from natural products is a critical and challenging task in drug discovery pipelines. Besides commonly used bio-guided screening approaches, affinity selection strategy coupled with liquid chromatography or mass spectrometry, known as ligand fishing, has been gaining increasing interest from researchers. In this review, we summarized this emerging strategy and categorized those methods as off-line or on-line mode according to their features. The separation principles of ligand fishing were introduced based on distinct analytical techniques, including biochromatography, capillary electrophoresis, ultrafiltration, equilibrium dialysis, microdialysis, and magnetic beads...
November 11, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27834921/functional-components-of-carob-fruit-linking-the-chemical-and-biological-space
#19
REVIEW
Vlasios Goulas, Evgenios Stylos, Maria V Chatziathanasiadou, Thomas Mavromoustakos, Andreas G Tzakos
The contribution of natural products to the drug-discovery pipeline has been remarkable since they have served as a rich source for drug development and discovery. Natural products have adapted, during the course of evolution, optimum chemical scaffolds against a wide variety of diseases, including cancer and diabetes. Advances in high-throughput screening assays, assisted by the continuous development on the instrumentation's capabilities and omics, have resulted in charting a large chemical and biological space of drug-like compounds, originating from natural sources...
November 10, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27832792/gout-will-the-king-of-diseases-be-the-first-rheumatic-disease-to-be-cured
#20
EDITORIAL
Jasvinder A Singh
Gout is the most common inflammatory arthritis in adults in the Western world. Characterized by hyperuricemia and the effects of acute and chronic inflammation in joints and bursa, gout leads to an agonizing, chronically painful arthritis. Arthritis can also be accompanied by urate nephropathy and subcutaneous urate deposits (tophi). Exciting new developments in the last decade have brought back the focus on this interesting, crystal-induced chronic inflammatory condition. New insights include the role of NALP3 inflammasome-induced inflammation in acute gout, the characterization of diagnostic signs on ultrasound and dual-energy computed tomography imaging modalities, the recognition of target serum urate less than 6 mg/day as the goal for urate-lowering therapies, and evidence-based treatment guidelines...
November 11, 2016: BMC Medicine
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