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Pipeline drugs

John F Brothers, Matthew Ung, Renan Escalante-Chong, Jermaine Ross, Jenny Zhang, Yoonjeong Cha, Andrew Lysaght, Jason Funt, Rebecca Kusko
The tremendous expansion of data analytics and public and private big datasets presents an important opportunity for pre-clinical drug discovery and development. In the field of life sciences, the growth of genetic, genomic, transcriptomic and proteomic data is partly driven by a rapid decline in experimental costs as biotechnology improves throughput, scalability, and speed. Yet far too many researchers tend to underestimate the challenges and consequences involving data integrity and quality standards. Given the effect of data integrity on scientific interpretation, these issues have significant implications during preclinical drug development...
March 15, 2018: Biochemical Pharmacology
Guillermo de Anda-Jáuregui, Kai Guo, Brett A McGregor, Junguk Hur
The quintessential biological response to disease is inflammation. It is a driver and an important element in a wide range of pathological states. Pharmacological management of inflammation is therefore central in the clinical setting. Anti-inflammatory drugs modulate specific molecules involved in the inflammatory response; these drugs are traditionally classified as steroidal and non-steroidal drugs. However, the effects of these drugs are rarely limited to their canonical targets, affecting other molecules and altering biological functions with system-wide effects that can lead to the emergence of secondary therapeutic applications or adverse drug reactions (ADRs)...
2018: Frontiers in Physiology
Sheikh Arslan Sehgal, Mirza A Hammad, Rana Adnan Tahir, Hafiza Nisha Akram, Faheem Ahmad
BACKGROUND: As the number of elderly persons increases, neurodegenerative diseases are becoming ubiquitous. There is currently a great need for knowledge concerning management of old-age neurodegenerative diseases; the most important of which are: Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, and Huntington's disease. OBJECTIVE: To summarize the potential of computationally predicted molecules and targets against neurodegenerative diseases...
March 15, 2018: Current Neuropharmacology
David F Driscoll
The incidence of antimicrobial resistance (AMR) worldwide is increasing as the pipeline for the development of new chemotherapeutic entities is decreasing. Clearly, overexposure to antibiotics, including excessive dosing, is a key factor that fuels AMR. In fact, most of the new antibacterial agents under development are derivatives of existing classes of antibiotics. Novel approaches involving unique antimicrobial combinations, targets, and/or delivery systems are under intense investigation. An innovative combination of active pharmaceutical ingredients (APIs) consisting of antimicrobial drug(s), krill-oil-based phospholipids, and omega-3 fatty acid triglycerides, that may extend the therapeutic viability of currently effective antibiotics, at least until new chemical entities are introduced, is described...
March 10, 2018: Antibiotics
A Samdani, Umashankar Vetrivel
High throughput virtual screening plays a crucial role in hit identification during the drug discovery process. With the rapid increase in the chemical libraries, virtual screening process becomes computationally challenging, thereby posing a demand for efficiently parallelized software pipelines. Here we present a GNU Parallel based pipeline-POAP that is programmed to run Open Babel and AutoDock suite under highly optimized parallelization. The ligand preparation module is a unique feature in POAP, as it offers extensive options for geometry optimization, conformer generation, parallelization and also quarantines erroneous datasets for seamless operation...
March 1, 2018: Computational Biology and Chemistry
Ken Garber
No abstract text is available yet for this article.
March 9, 2018: Nature Reviews. Drug Discovery
Wen He, Shanrong Zhao, Chi Zhang, Michael S Vincent, Baohong Zhang
Sequencing of transcribed RNA molecules (RNA-Seq) has been used wildly for studying cell transcriptomes in bulk or at the single-cell level (Wang et al., Nat Rev Genet, 10:57-63, 2009; Ozsolak and Milos, Nat Rev Genet, 12:87-98, 2011; Sandberg, Nat Methods, 11:22-24, 2014) and is becoming the de facto technology for investigating gene expression level changes in various biological conditions, on the time course, and under drug treatments. Furthermore, RNA-Seq data helped identify fusion genes that are related to certain cancers (Maher et al...
2018: Methods in Molecular Biology
Katherine Smith Fornili
The purpose of this column is to summarize important aspects of the racialized War on Drugs, including (a) the school-to-prison pipeline, (b) the for-profit prison system ("prison industrial complex"), (c) racialized mass incarceration, and (d) the disproportionately negative impact of the War on Drugs on families and communities of color. Analysis of critical race theory (CRT), the study of the relationships between race, racism, and power, will provide a cohesive framework for examining these four aspects...
January 2018: Journal of Addictions Nursing
Francesco Masia, Iestyn Pope, Peter Watson, Wolfgang Langbein, Paola Borri
Microscopy based high-content and high-throughput analysis of cellular systems plays a central role in drug discovery. However, for contrast and specificity, the majority of assays require a fluorescent readout which always comes with the risk of alteration of the true biological conditions. In this work, we demonstrate a label-free imaging platform which combines chemically-specific hyperspectral coherent anti-Stokes Raman scattering microscopy with sparse sampling and Bessel beam illumination. This enabled us to screen multi-well plates at high speed while retaining the high-content chemical analysis of hyperspectral imaging...
March 5, 2018: Analytical Chemistry
Gitanjali Srivastava, Caroline Apovian
PURPOSE OF REVIEW: Obesity is a global health crisis with detrimental effects on all organ systems leading to worsening disease state and rising costs of care. Persons with obesity failing lifestyle therapies need to be escalated to appropriate pharmacological treatment modalities, medical devices, and/or bariatric surgery if criteria are met and more aggressive intervention is needed. The progression of severe obesity in the patient population coupled with related co-morbidities necessitates the development of novel therapies for the treatment of obesity...
March 5, 2018: Current Obesity Reports
Joanne Young, Yoran Margaron, Mathieu Fernandes, Eve Duchemin-Pelletier, Joris Michaud, Mélanie Flaender, Oana Lorintiu, Sébastien Degot, Pauline Poydenot
Despite the need for more effective drug treatments to address muscle atrophy and disease, physiologically accurate in vitro screening models and higher information content preclinical assays that aid in the discovery and development of novel therapies are lacking. To this end, MyoScreen was developed: a robust and versatile high-throughput high-content screening (HT/HCS) platform that integrates a physiologically and pharmacologically relevant micropatterned human primary skeletal muscle model with a panel of pertinent phenotypic and functional assays...
March 1, 2018: SLAS Discovery
Syed S Hassan, Syed B Jamal, Leandro G Radusky, Sandeep Tiwari, Asad Ullah, Javed Ali, Behramand, Paulo V S D de Carvalho, Rida Shams, Sabir Khan, Henrique C P Figueiredo, Debmalya Barh, Preetam Ghosh, Artur Silva, Jan Baumbach, Richard Röttger, Adrián G Turjanski, Vasco A C Azevedo
Diphtheria is an acute and highly infectious disease, previously regarded as endemic in nature but vaccine-preventable, is caused by Corynebacterium diphtheriae (Cd). In this work, we used an in silico approach along the 13 complete genome sequences of C. diphtheriae followed by a computational assessment of structural information of the binding sites to characterize the "pocketome druggability." To this end, we first computed the "modelome" (3D structures of a complete genome) of a randomly selected reference strain Cd NCTC13129; that had 13,763 open reading frames (ORFs) and resulted in 1,253 (∼9%) structure models...
2018: Frontiers in Genetics
Tobias Atkin, Stefano Comai, Gabriella Gobbi
Although the GABAergic benzodiazepines (BZDs) and Z-drugs (zolpidem, zopiclone, and zaleplon) are FDA-approved for insomnia disorders with a strong evidence base, they have many side effects, including cognitive impairment, tolerance, rebound insomnia upon discontinuation, car accidents/falls, abuse, and dependence liability. Consequently, the clinical use of off-label drugs and novel drugs that do not target the GABAergic system is increasing. The purpose of this review is to analyze the neurobiological and clinical evidence of pharmacological treatments of insomnia, excluding the BZDs and Z-drugs...
April 2018: Pharmacological Reviews
Jason R Guercio, Jason E Kralic, Eric J Marrotte, Michael L James
CONTEXT: Current treatment of spinal cord injury (SCI) focuses on cord stabilization to prevent further injury, rehabilitation, management of non-motor symptoms, and prevention of complications. Currently, no approved treatments are available, and limited treatment options exist for symptoms and complications associated with chronic SCI. This review describes the pharmacotherapy landscape in SCI from both commercial and research and development (R&D) standpoints through March 2015...
February 27, 2018: Journal of Spinal Cord Medicine
Benjamin J Drapkin, Julie George, Camilla L Christensen, Mari Mino-Kenudson, Ruben Dries, Tilak Sundaresan, Sarah Phat, David T Myers, Jun Zhong, Peter Igo, Mehlika H Hazar-Rethinam, Joseph A LiCausi, Maria Gomez-Caraballo, Marina Kem, Kandarp N Jani, Roxana Azimi, Nima Abedpour, Roopika Menon, Sotirios Lakis, Rebecca S Heist, Reinhard Büttner, Stefan Haas, Lecia V Sequist, Alice T Shaw, Kwok-Kin Wong, Aaron N Hata, Mehmet Toner, Shyamala Maheswaran, Daniel A Haber, Martin Peifer, Nicholas Dyson, Roman K Thomas, Anna F Farago
Small cell lung cancer (SCLC) patient-derived xenografts (PDXs) can be generated from biopsies or circulating tumor cells (CTCs), though scarcity of tissue and low efficiency of tumor growth have previously limited these approaches. Applying an established clinical-translational pipeline for tissue collection and an automated microfluidic platform for CTC-enrichment, we generated 17 biopsy-derived PDXs and 17 CTC-derived PDXs in a two-year timeframe, at 89% and 38% efficiency, respectively. Whole exome sequencing showed that somatic alterations are stably maintained between patient tumors and PDXs...
February 26, 2018: Cancer Discovery
Michelle M Butler, Samanthi L Waidyarachchi, Kristie L Connolly, Ann E Jerse, Weirui Chai, Richard E Lee, Stephan A Kohlhoff, Dean L Shinabarger, Terry L Bowlin
Bacterial sexually transmitted infections are widespread and common, with Neisseria gonorrhoeae (gonorrhea) and Chlamydia trachomatis (chlamydia) being the two most frequent causes. If left untreated, both infections can cause pelvic inflammatory disease, infertility, ectopic pregnancy and other sequelae. The recommended treatment for gonorrhea is ceftriaxone plus azithromycin (to empirically treat chlamydial co-infections). Antibiotic resistance to all existing therapies has developed in gonorrheal infections...
February 26, 2018: Antimicrobial Agents and Chemotherapy
Joanna C Evans, Valerie Mizrahi
Claiming close to two million lives each year, tuberculosis is now the leading cause of death from an infectious disease. The rise in number of Mycobacterium tuberculosis (Mtb) strains resistant to existing TB drugs has underscored the urgent need to develop new antimycobacterials with novel mechanisms of action. To meet this need, a drug pipeline has been established that is populated with new and repurposed drugs. Recent advances in identifying molecules with inhibitory activity against Mtb under conditions modelled on those encountered during infection, and in elucidating their mechanisms of action, have primed the pipeline with promising drug/target couples, hit compounds and new targets...
February 23, 2018: Current Opinion in Microbiology
Karthikeyan Muthusamy, Selvaraman Nagamani
Pharmacogenetics and pharmacogenomics have become presumptive with advancements in next-generation sequencing technology. In complex diseases, distinguishing the feasibility of pathogenic and neutral disease-causing variants is a time consuming and expensive process. Recent drug research and development processes mainly rely on the relationship between the genotype and phenotype through Single nucleotide polymorphisms (SNPs). The SNPs play an indispensable role in elucidating the individual's vulnerability to disease and drug response...
February 12, 2018: Journal of Molecular Graphics & Modelling
Paul McVeigh, Erin McCammick, Paul McCusker, Duncan Wells, Jane Hodgkinson, Steve Paterson, Angela Mousley, Nikki J Marks, Aaron G Maule
G protein-coupled receptors (GPCRs) are established drug targets. Despite their considerable appeal as targets for next-generation anthelmintics, poor understanding of their diversity and function in parasitic helminths has thwarted progress towards GPCR-targeted anti-parasite drugs. This study facilitates GPCR research in the liver fluke, Fasciola hepatica, by generating the first profile of GPCRs from the F. hepatica genome. Our dataset describes 147 high confidence GPCRs, representing the largest cohort of GPCRs, and the largest set of in silico ligand-receptor predictions, yet reported in any parasitic helminth...
February 5, 2018: International Journal for Parasitology, Drugs and Drug Resistance
Bashir Sajo Mienda, Rabiu Salihu, Aliyu Adamu, Shehu Idris
The growing number of multidrug-resistant pathogenic bacteria is becoming a world leading challenge for the scientific community and for public health. However, advances in high-throughput technologies and whole-genome sequencing of bacterial pathogens make the construction of bacterial genome-scale metabolic models (GEMs) increasingly realistic. The use of GEMs as an alternative platforms will expedite identification of novel unconditionally essential genes and enzymes of target organisms with existing and forthcoming GEMs...
February 22, 2018: Future Microbiology
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