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Assay and Drug Development Technologies

Kendy Eduardo Urdaneta, María Andrea Castillo, Nola Montiel, Neomar Semprún-Hernández, Nicola Antonucci, Dario Siniscalco
Over the years, scientific researches have validated the healing benefits of many psychopharmacotherapeutic plant-based drugs to ameliorate psychiatric disorders. In contrast, the use of chemical procedures to isolate and purify specific compounds from plants that have been used to treat autism spectrum disorders (ASDs) and its clinical features may contribute to improve the quality of life of many patients. Also, herbal pharmacological treatments could improve the core symptoms of autism with fewer side effects...
November 14, 2018: Assay and Drug Development Technologies
Hermann A M Mucke
No abstract text is available yet for this article.
October 26, 2018: Assay and Drug Development Technologies
Priscila Cristina Bartolomeu Halicki, Gabriela Hädrich, Raphael Boschero, Laís Andrade Ferreira, Andrea von Groll, Pedro Eduardo Almeida da Silva, Cristiana Lima Dora, Daniela Fernandes Ramos
Tuberculosis (TB) is considered an emergency global public health, mainly due to the TB-HIV co-infection, bacillus dormancy stage, and emergence of resistant strains. In addition, the therapeutic toxicity and its pharmacokinetic interactions with other drugs may influence treatment non-compliance, low serum concentration of drugs, and, consequently, treatment failure. Strategies using nanotechnology represent a new tool for the therapy, since they are effective delivery systems due to the possibility of solubilization of hydrophobic compounds, enable the production of formulations for oral use, and, in addition, increase bioavailability of drugs...
October 16, 2018: Assay and Drug Development Technologies
Anton Simeonov, Mindy I Davis, Doug Auld
No abstract text is available yet for this article.
October 2018: Assay and Drug Development Technologies
Hermann A M Mucke
No abstract text is available yet for this article.
October 2018: Assay and Drug Development Technologies
Pia Hansson, Helen Boyd, Ian L Dale, Göran Dahl, Felix Nicolaus, Wayne Bowen, Klaus Doering, Colin Dunsmore, Graham Cotton, Helena Lindmark
Fluorescence assay technologies are commonly used in high-throughput screening because of their sensitivity and ease of use. Different technologies have their characteristics and the rationale for choosing one over the other can differ between projects because of factors such as availability of reagents, assay performance, and cost. Another important factor to consider is the assay susceptibility to artifacts, which is almost as important as the ability of the assay to pick up active compounds. Spending time and money on false positives or missing the opportunity to build chemistry around false negatives is something that every drug project tries to avoid...
October 2018: Assay and Drug Development Technologies
Camilo J Morfa, Daniel Bassoni, Andras Szabo, Danielle McAnally, Haleli Sharir, Becky L Hood, Stefan Vasile, Tom Wehrman, Jane Lamerdin, Layton H Smith
G-protein-coupled receptors (GPCRs) have varying and diverse physiological roles, transmitting signals from a range of stimuli, including light, chemicals, peptides, and mechanical forces. More than 130 GPCRs are orphan receptors (i.e., their endogenous ligands are unknown), representing a large untapped reservoir of potential therapeutic targets for pharmaceutical intervention in a variety of diseases. Current deorphanization approaches are slow, laborious, and usually require some in-depth knowledge about the receptor pharmacology...
October 2018: Assay and Drug Development Technologies
Tim W G M Spitters, Parker L Andersen, Chloé Martel, Patrick Vermette
The lack of understanding on how to treat pancreas-related diseases and develop new therapeutics is partly due to the unavailability of appropriate models. In vitro models fail to provide a physiological environment. Testing new drug targets in these models can give rise to bias and misleading results. Therefore, we developed an in vivo model for drug testing on full pancreatic digests, which maintains the interactions between endo- and exocrine tissues and allows retrieving the samples for further analyses...
August 14, 2018: Assay and Drug Development Technologies
Tara Zakerali, Sajad Shahbazi
Herbal remedies and phytochemicals have been used in traditional medicine. Most of the herbs used in human diet have some major effective elements that can affect various pathways in the human body and play a therapeutic role in healing disorders or diseases. Among the inflammatory diseases, worldwide common disorders possess well-known pathways that can be controlled by diet and behavior. There are some well-established targets that are used for anti-inflammatory drugs like cyclooxygenase type 1 and 2 (COX-1 and COX-2), lipoxygenase, prostaglandin D2 receptor, DP1, CRTH2, and so on...
August 14, 2018: Assay and Drug Development Technologies
(no author information available yet)
No abstract text is available yet for this article.
August 2018: Assay and Drug Development Technologies
Oliver Dürr, Elvis Murina, Daniel Siegismund, Vasily Tolkachev, Stephan Steigele, Beate Sick
Deep convolutional neural networks show outstanding performance in image-based phenotype classification given that all existing phenotypes are presented during the training of the network. However, in real-world high-content screening (HCS) experiments, it is often impossible to know all phenotypes in advance. Moreover, novel phenotype discovery itself can be an HCS outcome of interest. This aspect of HCS is not yet covered by classical deep learning approaches. When presenting an image with a novel phenotype to a trained network, it fails to indicate a novelty discovery but assigns the image to a wrong phenotype...
August 2018: Assay and Drug Development Technologies
Jin-Shu He, Priscilla Soo, Maurits Evers, Kate M Parsons, Nadine Hein, Katherine M Hannan, Ross D Hannan, Amee J George
The nucleolus is a dynamic subnuclear compartment that has a number of different functions, but its primary role is to coordinate the production and assembly of ribosomes. For well over 100 years, pathologists have used changes in nucleolar number and size to stage diseases such as cancer. New information about the nucleolus' broader role within the cell is leading to the development of drugs which directly target its structure as therapies for disease. Traditionally, it has been difficult to develop high-throughput image analysis pipelines to measure nucleolar changes due to the broad range of morphologies observed...
August 2018: Assay and Drug Development Technologies
Myles Fennell, Kaylene J Simpson
No abstract text is available yet for this article.
August 2018: Assay and Drug Development Technologies
Ashley T Fancher, Yun Hua, Daniel P Camarco, David A Close, Christopher J Strock, Paul A Johnston
Twenty percent of prostate cancer (PCa) patients develop a noncurable drug-resistant form of the disease termed castration-resistant prostate cancer (CRPC). Overexpression of Androgen Receptor (AR) coactivators such as transcriptional intermediary factor 2 (TIF2) is associated with poor CRPC patient outcomes. We describe the implementation of the AR-TIF2 protein-protein interaction biosensor (PPIB) assay in a high-content screening (HCS) campaign of 143,535 compounds. The assay performed robustly and reproducibly and enabled us to identify compounds that inhibited dihydrotestosterone (DHT)-induced AR-TIF2 protein-protein interaction (PPI) formation or disrupted preexisting AR-TIF2 PPIs...
August 2018: Assay and Drug Development Technologies
Steven A Haney
No abstract text is available yet for this article.
August 2018: Assay and Drug Development Technologies
Adrien Nougarède, Chloé Tesnière, Jarkko Ylanko, Ruth Rimokh, Germain Gillet, David W Andrews
In response to a variety of insults the unfolded protein response (UPR) is a major cell program quickly engaged to promote either cell survival or if stress levels cannot be relieved, apoptosis. UPR relies on three major pathways, named from the endoplasmic reticulum (ER) resident proteins IRE1α, PERK, and ATF6 that mediate response. Current tools to measure the activation of these ER stress response pathways in mammalian cells are cumbersome and not compatible with high-throughput imaging. In this study, we present IRE1α and PERK sensors with improved sensitivity, based on the canonical events of xbp1 splicing and ATF4 translation at ORF3...
August 2018: Assay and Drug Development Technologies
William D Klaren, Ivan Rusyn
Skeletal muscle-associated toxicity is an underresearched area in the field of high-throughput toxicity screening; hence, the potential adverse effects of drugs and chemicals on skeletal muscle are largely unknown. Novel organotypic microphysiological in vitro models are being developed to replicate the contractile function of skeletal muscle; however, the throughput and a need for specialized equipment may limit the utility of these tissue chip models for screening. In addition, recent developments in stem cell biology have resulted in the generation of induced pluripotent stem cell (iPSC)-derived skeletal myoblasts that enable high-throughput in vitro screening...
August 2018: Assay and Drug Development Technologies
Norazwana Samat, Mei Fong Ng, Nur Faizah Ruslan, Kazuhide Shaun Okuda, Pei Jean Tan, Vyomesh Patel
Natural products are prolific producers of diverse chemical scaffolds, which have yielded several clinically useful drugs. However, the complex features of natural products present challenges for identifying bioactive molecules using high-throughput screens. For most assays, measured endpoints are either colorimetric or luminescence based. Thus, the presence of the major metabolites, tannins, and chlorophylls, in natural products could potentially interfere with these measurements to give either false-positive or false-negative hits...
July 9, 2018: Assay and Drug Development Technologies
Ainhoa Nieto, Virneliz Fernández-Vega, Timothy P Spicer, Emmanuel Sturchler, Pramisha Adhikari, Nicole Kennedy, Sean Mandat, Peter Chase, Louis Scampavia, Thomas Bannister, Peter Hodder, Patricia H McDonald
GPR119 drug discovery efforts in the pharmaceutical industry for the treatment of type 2 diabetes mellitus (T2DM) and obesity, were initiated based on its restricted distribution in pancreas and GI tract, and its possible role in glucose homeostasis. While a number of lead series have emerged, the pharmacological endpoints they provide have not been clear. In particular, many lead series have demonstrated loss of efficacy and significant toxic side effects. Thus, we sought to identify novel, potent, positive modulators of GPR119...
July 2018: Assay and Drug Development Technologies
Aaron Wilson, John Concannon, Doug Auld
No abstract text is available yet for this article.
July 2018: Assay and Drug Development Technologies
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