keyword
MENU ▼
Read by QxMD icon Read
search

"Drug development"

keyword
https://www.readbyqxmd.com/read/28346578/association-of-plasma-neurofilament-light-with-neurodegeneration-in-patients-with-alzheimer-disease
#1
Niklas Mattsson, Ulf Andreasson, Henrik Zetterberg, Kaj Blennow
Importance: Existing cerebrospinal fluid (CSF) or imaging (tau positron emission tomography) biomarkers for Alzheimer disease (AD) are invasive or expensive. Biomarkers based on standard blood test results would be useful in research, drug development, and clinical practice. Plasma neurofilament light (NFL) has recently been proposed as a blood-based biomarker for neurodegeneration in dementias. Objective: To test whether plasma NFL concentrations are increased in AD and associated with cognitive decline, other AD biomarkers, and imaging evidence of neurodegeneration...
March 27, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28346107/a-high-throughput-method-for-measuring-drug-residence-time-using-the-transcreener-adp-assay
#2
Meera Kumar, Robert G Lowery
Analysis of drug-target residence times during drug development can result in improved efficacy, increased therapeutic window, and reduced side effects. Residence time can be estimated as the reciprocal of the dissociation rate ( koff) of an inhibitor from its target. The traditional methods for measuring koff require synthesis of labeled ligands or low-throughput label-free methods. To provide an alternative that is better suited to an automated high-throughput screening (HTS) environment, we adapted a classic "jump dilution" catalytic assay method for determination of koff values for kinase inhibitor drugs...
February 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346087/pubchem-bioassay
#3
Yanli Wang, Tiejun Cheng, Stephen H Bryant
High-throughput screening (HTS) is now routinely conducted for drug discovery by both pharmaceutical companies and screening centers at academic institutions and universities. Rapid advance in assay development, robot automation, and computer technology has led to the generation of terabytes of data in screening laboratories. Despite the technology development toward HTS productivity, fewer efforts were devoted to HTS data integration and sharing. As a result, the huge amount of HTS data was rarely made available to the public...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28344021/pharmaceutical-cocrystals-salts-and-multicomponent-systems-intermolecular-interactions-and-property-based-design
#4
REVIEW
David J Berry, Jonathan W Steed
As small molecule drugs become harder to develop and less cost effective for patient use, efficient strategies for their property improvement become increasingly important to global health initiatives. Improvements in the physical properties of Active Pharmaceutical Ingredients (APIs), without changes in the covalent chemistry, have long been possible through the application of binary component solids. This was first achieved through the use of pharmaceutical salts, within the last 10-15years with cocrystals and more recently coamorphous systems have also been consciously applied to this problem...
March 23, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28344002/establishment-of-a-human-blood-brain-barrier-co-culture-model-mimicking-the-neurovascular-unit-using-induced-pluri-and-multipotent-stem-cells
#5
Antje Appelt-Menzel, Alevtina Cubukova, Katharina Günther, Frank Edenhofer, Jörg Piontek, Gerd Krause, Tanja Stüber, Heike Walles, Winfried Neuhaus, Marco Metzger
In vitro models of the human blood-brain barrier (BBB) are highly desirable for drug development. This study aims to analyze a set of ten different BBB culture models based on primary cells, human induced pluripotent stem cells (hiPSCs), and multipotent fetal neural stem cells (fNSCs). We systematically investigated the impact of astrocytes, pericytes, and NSCs on hiPSC-derived BBB endothelial cell function and gene expression. The quadruple culture models, based on these four cell types, achieved BBB characteristics including transendothelial electrical resistance (TEER) up to 2,500 Ω cm(2) and distinct upregulation of typical BBB genes...
March 22, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28342897/dose-response-effect-of-acute-phencyclidine-on-functional-connectivity-and-dopamine-levels-and-their-association-with-schizophrenia-like-symptom-classes-in-rat
#6
Jaakko Paasonen, Raimo A Salo, Jouni Ihalainen, Juuso V Leikas, Katja Savolainen, Marko Lehtonen, Markus M Forsberg, Olli Gröhn
Current drug treatments for schizophrenia (SCZ) can alleviate positive symptoms, but have little effect on the negative symptoms and cognitive deficits that are difficult to translate into preclinical models for drug development. Therefore, we aimed to determine the dose-response effects of acute phencyclidine (PCP, 1.0-5.0 mg/kg) on rat brain connectivity and detect markers for different SCZ-like symptoms. Pharmacological functional magnetic resonance imaging (phMRI) and microdialysis were used to investigate PCP-induced effects on functional connectivity (FC) and dopamine levels, respectively...
March 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28342833/a-high-density-cho-s-transient-transfection-system-comparison-of-expicho-and-expi293
#7
Nina K Jain, Susan Barkowski-Clark, Richard Altman, Krista Johnson, Fang Sun, Jonathan Zmuda, Chao Yan Liu, Adriana Kita, Ryan Schulz, Alyssa Neill, Robert Ballinger, Rekha Patel, Jian Liu, Alinafe Mpanda, Brian Huta, Henry Chiou, Walter Voegtli, Tadas Panavas
Chinese Hamster Ovary (CHO) cells are the principal mammalian host used for stable cell line generation and biotherapeutic protein production. Until recently, production of milligrams to grams of protein in CHO transient systems was challenging. As such, Human Embryonic Kidney (HEK293) cells are the most common mammalian cell type used for transient transfection. The post-translational modifications (PTMs) of a protein are dictated in part by the cell line used for expression, and changes in PTMs have been shown to affect both the activity and biophysical properties of proteins...
March 22, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28342305/metabolic-profiling-of-nuciferine-in-rat-urine-plasma-bile-and-feces-after-oral-administration-using-ultra-high-performance-liquid-chromatography-diode-array-detection-quadrupole-time-of-flight-mass-spectrometry
#8
Xiao-Lei Wu, Ming-Jiang Wu, Xin-Ze Chen, Hao-Ling Ma, Li-Qin Ding, Feng Qiu, Qin Pan, De-Qin Zhang
Nuciferine, a major alkaloid found in Nelumbinis Folium, exhibits a broad spectrum of bioactivities, such as antiobesity, anti-diabetes and anti-inflammatory. However, many research regarding nuciferine focused on the extraction, isolation and biological activity, the metabolism is not comprehensively explained in vivo. Thence, the present of this paper is to establish a simple method for speculating metabolites of nuciferine. A total of 15 metabolites were detected and tentatively identified through ultra high performance liquid chromatography-diode array detection-quadrupole time-of-flight mass spectrometry (UHPLC-DAD-QTOF-MS), including 7 new metabolites...
March 18, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28342149/identification-and-preparation-of-a-novel-chemokine-receptor-binding-domain-in-the-cytoplasmic-regulator-frount
#9
Akihiro Sonoda, Sosuke Yoshinaga, Kaori Yunoki, Soichiro Ezaki, Kotaro Yano, Mitsuhiro Takeda, Etsuko Toda, Yuya Terashima, Kouji Matsushima, Hiroaki Terasawa
FROUNT is a cytoplasmic protein that binds to the membrane-proximal C-terminal regions (Pro-Cs) of chemokine receptors, CCR2 and CCR5. The FROUNT-chemokine receptor interactions play a pivotal role in the migration of inflammatory immune cells, indicating the potential of FROUNT as a drug target for inflammatory diseases. To provide the foundation for drug development, structural information of the Pro-C binding region of FROUNT is desired. Here, we defined the novel structural domain (FNT-CB), which mediates the interaction with the chemokine receptors...
March 24, 2017: Molecular Biotechnology
https://www.readbyqxmd.com/read/28341945/translational-value-of-drug-discrimination-with-typical-and-atypical-antipsychotic-drugs
#10
Joseph H Porter, Kevin A Webster, Adam J Prus
This chapter focuses on the translational value of drug discrimination as a preclinical assay for drug development. In particular, the importance of two factors, i.e., training dose and species, for drug discrimination studies with the atypical antipsychotic clozapine is examined. Serotonin receptors appear to be an important pharmacological mechanism mediating clozapine's discriminative cue in both rats and mice, although differences are clearly evident as antagonism of cholinergic muscarinic receptors is important in rats at a higher training dose (5...
March 25, 2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28341403/thiazolidine-derivatives-as-potent-and-selective-inhibitors-of-the-pim-kinase-family
#11
Carole J R Bataille, Méabh B Brennan, Simon Byrne, Stephen G Davies, Matthew Durbin, Oleg Fedorov, Kilian V M Huber, Alan M Jones, Stefan Knapp, Gu Liu, Anna Nadali, Camilo E Quevedo, Angela J Russell, Roderick G Walker, Robert Westwood, Graham M Wynne
The PIM family of serine/threonine kinases have become an attractive target for anti-cancer drug development, particularly for certain hematological malignancies. Here, we describe the discovery of a series of inhibitors of the PIM kinase family using a high throughput screening strategy. Through a combination of molecular modeling and optimization studies, the intrinsic potencies and molecular properties of this series of compounds was significantly improved. An excellent pan-PIM isoform inhibition profile was observed across the series, while optimized examples show good selectivity over other kinases...
February 28, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28340622/anti-plasmodial-activity-of-norcaesalpin-d-and-extracts-of-four-medicinal-plants-used-traditionally-for-treatment-of-malaria
#12
Ramadhani Selemani Omari Nondo, Mainen Julius Moshi, Paul Erasto, Pax Jessey Masimba, Francis Machumi, Abdul Waziri Kidukuli, Matthias Heydenreich, Denis Zofou
BACKGROUND: Malaria is an old life-threatening parasitic disease that is still affecting many people, mainly children living in sub-Saharan Africa. Availability of effective antimalarial drugs played a significant role in the treatment and control of malaria. However, recent information on the emergence of P. falciparum parasites resistant to one of the artemisinin-based combination therapies suggests the need for discovery of new drug molecules. Therefore, this study aimed to evaluate the antiplasmodial activity of extracts, fractions and isolated compound from medicinal plants traditionally used in the treatment of malaria in Tanzania...
March 24, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28340378/current-fda-approved-treatments-for-non-small-cell-lung-cancer-and-potential-biomarkers-for-its-detection
#13
REVIEW
Karla A Ruiz-Ceja, Yolanda I Chirino
BACKGROUND: Lung cancer is the leading worldwide cancer with almost 1.5 million deaths every year. Some drugs for lung cancer treatment have been available on the market for decades, but novel drugs have emerged promising better outcomes, especially for Non-Small Cell Lung Cancer (NSCLC), which represents 75% of lung cancer cases. However, how much do drugs have evolved for NSCLC treatment? Are they sharing the same mechanism of action? AIM: In this review we analyzed how the approved drugs by Federal Drug Agency for NSCLC have advanced in the last four decades identifying shared mechanism of action of medicines against NSCLC treatment and some of the potential biomarkers for early detection...
March 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28337147/3d-proximal-tubule-tissues-recapitulate-key-aspects-of-renal-physiology-to-enable-nephrotoxicity-testing
#14
Shelby M King, J William Higgins, Celina R Nino, Timothy R Smith, Elizabeth H Paffenroth, Casey E Fairbairn, Abigail Docuyanan, Vishal D Shah, Alice E Chen, Sharon C Presnell, Deborah G Nguyen
Due to its exposure to high concentrations of xenobiotics, the kidney proximal tubule is a primary site of nephrotoxicity and resulting attrition in the drug development pipeline. Current pre-clinical methods using 2D cell cultures and animal models are unable to fully recapitulate clinical drug responses due to limited in vitro functional lifespan, or species-specific differences. Using Organovo's proprietary 3D bioprinting platform, we have developed a fully cellular human in vitro model of the proximal tubule interstitial interface comprising renal fibroblasts, endothelial cells, and primary human renal proximal tubule epithelial cells to enable more accurate prediction of tissue-level clinical outcomes...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28336557/catechins-as-potential-mediators-of-cardiovascular-health
#15
REVIEW
Daniel R Mangels, Emile R Mohler
The impact of diet on cardiovascular disease has become an increasingly relevant topic as ongoing epidemiological evidence continues to demonstrate clear associations with disease burden and mortality. Certain diets, such as those high in sodium and saturated fat, are associated with cardiovascular disease states, while other diets can be cardioprotective. However, there is limited knowledge on how the micro- and macronutrients within such cardioprotective diets afford their benefits. One such micronutrient is the catechin class, which are naturally occurring compounds in plant foods, such as teas, cocoa, wine, pears, and apples...
March 23, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28335658/dopamine-antagonists-for-treatment-resistance-in-autism-spectrum-disorders-review-and-focus-on-bdnf-stimulators-loxapine-and-amitriptyline
#16
Jessica A Hellings, L Eugene Arnold, Joan Han
Drug development is urgently needed for individuals with autism spectrum disorders (ASD) and psychiatric comorbidity, which often presents as aggression and self-injury. At the same time, most psychiatric medications are drugs that have been repurposed following clinical observations of efficacy for a new treatment purpose. Areas Covered: This review aims to provide an overview of dopamine antagonists, including classical and atypical, as well as unconventional antipsychotics in ASD, since they are a mainstay of treatment for such problems...
March 24, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28334136/a-review-of-network-based-approaches-to-drug-repositioning
#17
Maryam Lotfi Shahreza, Nasser Ghadiri, Sayed Rasoul Mousavi, Jaleh Varshosaz, James R Green
Experimental drug development is time-consuming, expensive and limited to a relatively small number of targets. However, recent studies show that repositioning of existing drugs can function more efficiently than de novo experimental drug development to minimize costs and risks. Previous studies have proven that network analysis is a versatile platform for this purpose, as the biological networks are used to model interactions between many different biological concepts. The present study is an attempt to review network-based methods in predicting drug targets for drug repositioning...
February 27, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28334070/detection-of-drug-drug-interactions-through-data-mining-studies-using-clinical-sources-scientific-literature-and-social-media
#18
Santiago Vilar, Carol Friedman, George Hripcsak
Drug-drug interactions (DDIs) constitute an important concern in drug development and postmarketing pharmacovigilance. They are considered the cause of many adverse drug effects exposing patients to higher risks and increasing public health system costs. Methods to follow-up and discover possible DDIs causing harm to the population are a primary aim of drug safety researchers. Here, we review different methodologies and recent advances using data mining to detect DDIs with impact on patients. We focus on data mining of different pharmacovigilance sources, such as the US Food and Drug Administration Adverse Event Reporting System and electronic health records from medical institutions, as well as on the diverse data mining studies that use narrative text available in the scientific biomedical literature and social media...
February 17, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28333961/phytochemical-investigation-of-aloe-pulcherrima-roots-and-evaluation-for-its-antibacterial-and-antiplasmodial-activities
#19
Dele Abdissa, Girma Geleta, Ketema Bacha, Negera Abdissa
Medicinal plants with documented traditional uses remain an important source for the treatment of a wide range of ailments. Evidence shows that majority of the Ethiopian population are still dependent on traditional medicine. Aloe pulcherrima Gilbert & Sebsebe is one of the endemic Aloe species traditionally used for the treatment of malaria and wound healing in central, Southern and Northern part of Ethiopia. The aim of the current study was, therefore, to isolate active compounds from roots of A. pulcherrima and evaluate for their antibacterial and antiplasmodial activities using standard test strains...
2017: PloS One
https://www.readbyqxmd.com/read/28332132/redefining-the-role-of-biomarkers-in-heart-failure-trials-expert-consensus-document
#20
REVIEW
Frank Kramer, Hani N Sabbah, James J Januzzi, Faiez Zannad, J Peter van Tintelen, Erik B Schelbert, Raymond J Kim, Hendrik Milting, Richardus Vonk, Brien Neudeck, Richard Clark, Klaus Witte, Wilfried Dinh, Burkert Pieske, Javed Butler, Mihai Gheorghiade
Heart failure is a growing cardiovascular disease with significant epidemiological, clinical, and societal implications and represents a high unmet need. Strong efforts are currently underway by academic and industrial researchers to develop novel treatments for heart failure. Biomarkers play an important role in patient selection and monitoring in drug trials and in clinical management. The present review gives an overview of the role of available molecular, imaging, and device-derived digital biomarkers in heart failure drug development and highlights capabilities and limitations of biomarker use in this context...
March 23, 2017: Heart Failure Reviews
keyword
keyword
47312
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"