keyword
MENU ▼
Read by QxMD icon Read
search

New drug discovery

keyword
https://www.readbyqxmd.com/read/29792805/a-cheminformatic-insight-into-the-differences-between-terrestrial-and-marine-originated-natural-products
#1
Jun Shang, Ben Hu, Junmei Wang, Feng Zhu, Yu Kang, Dan Li, Huiyong Sun, De-Xin Kong, Tingjun Hou
This is a new golden age for the drug discovery based on natural products derived from both marine and terrestrial sources. Herein, a straightforward but important question is what are the major structural differences between marine natural products (MNPs) and terrestrial natural products (TNPs). To answer this question, we analyzed the important physicochemical properties, structural features and drug-likeness of the two types of natural products and discussed their differences from the perceptive of evolution...
May 24, 2018: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29792714/docking-screens-for-dual-inhibitors-of-disparate-drug-targets-for-parkinson-s-disease
#2
Mariama Jaiteh, Alexey Zeifman, Marcus Saarinen, Per Svenningsson, José M Brea, Maria Isabel Loza, Jens Carlsson
Modulation of multiple biological targets with a single drug can lead to synergistic therapeutic effects and has been demonstrated to be essential for efficient treatment of CNS disorders. However, rational design of compounds that interact with several targets is very challenging. Here, we demonstrate that structure-based virtual screening can guide the discovery of multi-target ligands of unrelated proteins relevant for Parkinson's disease. A library with 5.4 million molecules was docked to crystal structures of the A2A adenosine receptor (A2AAR) and monoamine oxidase B (MAO-B)...
May 24, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29792329/residual-complexity-does-impact-organic-chemistry-and-drug-discovery-the-case-of-rufomyazine-and-rufomycin
#3
Mary P Choules, Larry L Klein, David C Lankin, James B McAlpine, Sang-Hyun Cho, Jinhua Cheng, Hanki Lee, Joo-Won Suh, Birgit U Jaki, Scott G Franzblau, Guido F Pauli
Residual complexity (RC) involves the impact of subtle but critical structural and biological features on drug lead validation, including unexplained effects related to unidentified impurities. RC commonly plagues drug discovery efforts due to the inherent imperfections of chromatographic separation methods. The new diketopiperazine, rufomyazine (6), and the previously known antibiotic, rufomycin (7), represent a prototypical case of RC that (almost) resulted in the misassignment of biological activity. The case exemplifies that impurities well below the natural abundance of 13 C (1...
May 24, 2018: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29792109/computational-functional-genomics-based-approaches-in-analgesic-drug-discovery-and-repurposing
#4
Catharina Lippmann, Dario Kringel, Alfred Ultsch, Jörn Lötsch
Persistent pain is a major healthcare problem affecting a fifth of adults worldwide with still limited treatment options. The search for new analgesics increasingly includes the novel research area of functional genomics, which combines data derived from various processes related to DNA sequence, gene expression or protein function and uses advanced methods of data mining and knowledge discovery with the goal of understanding the relationship between the genome and the phenotype. Its use in drug discovery and repurposing for analgesic indications has so far been performed using knowledge discovery in gene function and drug target-related databases; next-generation sequencing; and functional proteomics-based approaches...
May 24, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29791525/2-3-8-trisubstituted-quinolines-with-antimalarial-activity
#5
Pablo D G Martinez, Susann H Krake, Maitia L Poggi, Simon F Campbell, Paul A Willis, Luiz C Dias
Combination therapy drugs are considered a fundamental way to control malaria as it mimimizes the risk of emergence of resistance to the individual partner drugs. Consequently, this type of therapy constitutes a driving force for the discovery of new drugs with different modes of action, since this will provide options for combining different drugs to achieve the optimum antimalarial treatment. In this context, a 2,3,8-trisubstitued quinoline compound was found in a high throughput screen (HTS) to show an excellent inhibition of P...
May 21, 2018: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/29790875/visible-light-induced-electropolymerization-of-suspended-hydrogel-bioscaffolds-in-a-microfluidic-chip
#6
Pan Li, Haibo Yu, Na Liu, Feifei Wang, Gwo-Bin Lee, Yuechao Wang, Lianqing Liu, Wen Jung Li
The development of microengineered hydrogels co-cultured with cells in vitro could advance in vivo bio-systems in both structural complexity and functional hierarchy, which holds great promise for applications in regenerative tissues or organs, drug discovery and screening, and bio-sensors or bio-actuators. Traditional hydrogel microfabrication technologies such as ultraviolet (UV) laser or multiphoton laser stereolithography and three-dimensional (3D) printing systems have advanced the development of 3D hydrogel micro-structures but need either expensive and complex equipment, or harsh material selection with limited photoinitiators...
May 23, 2018: Biomaterials Science
https://www.readbyqxmd.com/read/29789338/inner-workings-zebrafish-assay-forges-new-approach-to-drug-discovery
#7
Kim Smuga-Otto
No abstract text is available yet for this article.
May 22, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29788892/inhibition-of-glycolysis-and-glutaminolysis-emerging-drug-discovery-approach-to-combat-cancer
#8
Nicholas S Akins, Tanner C Nielson, Hoang V Le
Cancer cells have a very different metabolism from that of normal cells from which they are derived. Their metabolism is elevated, which allows them to sustain higher proliferative rate and resist some cell death signals. This phenomenon, known as the "Warburg effect", has become the focus of intensive efforts in the discovery of new therapeutic targets and new cancer drugs. Both glycolysis and glutaminolysis pathways are enhanced in cancer cells. While glycolysis is enhanced to satisfy the increasing energy demand of cancer cells, glutaminolysis is enhanced to provide biosynthetic precursors for cancer cells...
May 22, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29788787/review-of-bioactive-secondary-metabolites-from-marine-bryozoans-in-the-progress-of-new-drugs-discovery
#9
Xiang Rong Tian, Hai Feng Tang, Xiao Lin Tian, Jia Jun Hu, Li Li Huang, Kirk R Gustafson
Marine bryozoans play an important role for the discovery of novel bioactive compounds among marine organisms. In this review, we summarize 164 new secondary metabolites including macrocyclic lactones, sterols, alkaloids, sphingolipids and so forth from 24 marine bryozoans in the last two decades. The structural features, bioactivity, structure-activity relationship, mechanism and strategies to address the resupply of these scarce secondary metabolites are discussed. The structural and bioactive diversity of the secondary metabolites from marine bryozoans indicated the possibility of using these compounds, especially bryostatin 1 (1), bryostatin analog (BA1), alkaloids (50, 53, 127-128 and 134-139), sphingolipids sulfates (148 and 149) and sulfur-containing aromatic compound (160), as the starting points for new drug discovery...
May 23, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29787326/application-of-high-throughput-flow-cytometry-in-early-drug-discovery-an-astrazeneca-perspective
#10
Mei Ding, Roger Clark, Catherine Bardelle, Anna Backmark, Tyrrell Norris, Wendy Williams, Mark Wigglesworth, Rob Howes
Flow cytometry is a powerful tool providing multiparametric analysis of single cells or particles. The introduction of faster plate-based sampling technologies on flow cytometers has transformed the technology into one that has become attractive for higher throughput drug discovery screening. This article describes AstraZeneca's perspectives on the deployment and application of high-throughput flow cytometry (HTFC) platforms for small-molecule high-throughput screening (HTS), structure-activity relationship (SAR) and phenotypic screening, and antibody screening...
May 1, 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29786944/design-synthesis-and-evaluation-of-a-novel-series-of-inhibitors-reversing-p-glycoprotein-mediated-multidrug-resistance
#11
Hesham Ghaleb, Huilan Li, Mutta Kairuki, Qianqian Qiu, Xinzhou Bi, Chunxia Liu, Chen Liao, Jieming Li, Kamal Hezam, Wenlong Huang, Hai Qian
Multidrug resistance (MDR) is still the main barrier to attaining effective results with chemotherapy. Discovery of new chemo-reversal agents is needed to overcome MDR. Our study focused on a better way to obtain novel drugs with triazole rings that have an MDR-reversal ability through click chemistry. Among 20 developed compounds, compound 19 had a minimal cytotoxic effect compared to tariquidar and verapamil (VRP) and showed a higher reversal activity than VRP through increased accumulation in K562/A02 cells...
May 22, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29786430/galaxygpcrloop-template-based-and-ab-initio-structure-sampling-of-the-extracellular-loops-of-g-protein-coupled-receptors
#12
Jonghun Won, Gyu Rie Lee, Hahnbeom Park, Chaok Seok
The second extracellular loops (ECL2s) of G-protein-coupled receptors (GPCRs) are often involved in GPCR functions, and their structures have important implications in drug discovery. However, structure prediction of ECL2 is difficult because of its long length and the structural diversity among different GPCRs. In this study, a new ECL2 conformational sampling method involving both template-based and ab initio sampling was developed. Inspired by observation of similar ECL2 structures of closely related GPCRs, a template-based sampling method employing loop structure templates selected from the structure database was developed...
May 22, 2018: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29785561/reptb-a-gene-ontology-based-drug-repurposing-approach-for-tuberculosis
#13
Anurag Passi, Neeraj Kumar Rajput, David J Wild, Anshu Bhardwaj
Tuberculosis (TB) is the world's leading infectious killer with 1.8 million deaths in 2015 as reported by WHO. It is therefore imperative that alternate routes of identification of novel anti-TB compounds are explored given the time and costs involved in new drug discovery process. Towards this, we have developed RepTB. This is a unique drug repurposing approach for TB that uses molecular function correlations among known drug-target pairs to predict novel drug-target interactions. In this study, we have created a Gene Ontology based network containing 26,404 edges, 6630 drug and 4083 target nodes...
May 21, 2018: Journal of Cheminformatics
https://www.readbyqxmd.com/read/29785244/more-than-just-an-immunosuppressant-the-emerging-role-of-fty720-as-a-novel-inducer-of-ros-and-apoptosis
#14
REVIEW
Teruaki Takasaki, Kanako Hagihara, Ryosuke Satoh, Reiko Sugiura
Fingolimod hydrochloride (FTY720) is a first-in-class of sphingosine-1-phosphate (S1P) receptor modulator approved to treat multiple sclerosis by its phosphorylated form (FTY720-P). Recently, a novel role of FTY720 as a potential anticancer drug has emerged. One of the anticancer mechanisms of FTY720 involves the induction of reactive oxygen species (ROS) and subsequent apoptosis, which is largely independent of its property as an S1P modulator. ROS have been considered as a double-edged sword in tumor initiation/progression...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29785193/gallnuts-a-potential-treasure-in-anticancer-drug-discovery
#15
REVIEW
Jiayu Gao, Xiao Yang, Weiping Yin, Ming Li
Introduction. In the discovery of more potent and selective anticancer drugs, the research continually expands and explores new bioactive metabolites coming from different natural sources. Gallnuts are a group of very special natural products formed through parasitic interaction between plants and insects. Though it has been traditionally used as a source of drugs for the treatment of cancerous diseases in traditional and folk medicinal systems through centuries, the anticancer properties of gallnuts are barely systematically reviewed...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29783192/interaction-of-dna-and-mononucleotides-with-theophylline-investigated-using-electrochemical-biosensors-and-biosensing
#16
Katarína Nemčeková, Ján Labuda, Viktor Milata, Jana Blaškovičová, Jozef Sochr
The understanding of DNA-drug interaction mechanism is among the important aspects of biological studies for drug design, discovery and pharmaceutical development processes. Published rather detailed FTIR and UV-visible spectroscopic studies on the interactions of theophylline, theobromine and caffeine with calf thymus DNA have shown effective binding of these methylxanthine derivatives to DNA and RNA involving H-bonds. However, to our knowledge, there is no such investigation using electrochemical approach...
May 3, 2018: Bioelectrochemistry
https://www.readbyqxmd.com/read/29782894/screening-of-the-mmv-and-gsk-open-access-chemical-boxes-using-a-viability-assay-developed-against-the-kinetoplastid-crithidia-fasciculata
#17
Wakisa Kipandula, Simon A Young, Stuart A MacNeill, Terry K Smith
Diseases caused by the pathogenic kinetoplastids continue to incapacitate and kill hundreds of thousands of people annually throughout the tropics and sub-tropics. Unfortunately, in the countries where these neglected diseases occur, financial obstacles to drug discovery and technical limitations associated with biochemical studies impede the development of new, safe, easy to administer and effective drugs. Here we report the development and optimisation of a Crithidia fasciculata resazurin viability assay, which is subsequently used for screening and identification of anti-crithidial compounds in the MMV and GSK open access chemical boxes...
May 18, 2018: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/29782488/insight-into-small-molecule-binding-to-the-neonatal-fc-receptor-by-x-ray-crystallography-and-100-khz-magic-angle-spinning-nmr
#18
Daniel Stöppler, Alex Macpherson, Susanne Smith-Penzel, Nicolas Basse, Fabien Lecomte, Hervé Deboves, Richard D Taylor, Tim Norman, John Porter, Lorna C Waters, Marta Westwood, Ben Cossins, Katharine Cain, James White, Robert Griffin, Christine Prosser, Sebastian Kelm, Amy H Sullivan, David Fox, Mark D Carr, Alistair Henry, Richard Taylor, Beat H Meier, Hartmut Oschkinat, Alastair D Lawson
Aiming at the design of an allosteric modulator of the neonatal Fc receptor (FcRn)-Immunoglobulin G (IgG) interaction, we developed a new methodology including NMR fragment screening, X-ray crystallography, and magic-angle-spinning (MAS) NMR at 100 kHz after sedimentation, exploiting very fast spinning of the nondeuterated soluble 42 kDa receptor construct to obtain resolved proton-detected 2D and 3D NMR spectra. FcRn plays a crucial role in regulation of IgG and serum albumin catabolism. It is a clinically validated drug target for the treatment of autoimmune diseases caused by pathogenic antibodies via the inhibition of its interaction with IgG...
May 21, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29781349/recent-advances-in-targeting-protein-arginine-methyltransferase-enzymes-in-cancer-therapy
#19
Emily Smith, Wei Zhou, Polina Shindiapina, Said Sif, Chenglong Li, Robert A Baiocchi
Exploration in the field of epigenetics has revealed the diverse roles of the protein arginine methyltransferase (PRMT) family of proteins in multiple disease states. These findings have led to the development of specific inhibitors and discovery of several new classes of drugs with potential to treat both benign and malignant conditions. Areas covered: We provide an overview on the role of PRMT enzymes in healthy and malignant cells, highlighting the role of arginine methylation in specific pathways relevant to cancer pathogenesis...
May 21, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29781014/cat-elcca-catalyzing-drug-discovery-through-click-chemistry
#20
Amanda L Garner
Click chemistry has emerged as a powerful tool in our arsenal for unlocking new biology. This includes its utility in both chemical biology and drug discovery. An emerging application of click chemistry is in the development of biochemical assays for high-throughput screening to identify new chemical probes and drug leads. This Feature Article will discuss the advancements in click chemistry that were necessary for the development of a new class of biochemical assay, catalytic enzyme-linked click chemistry assay or cat-ELCCA...
May 21, 2018: Chemical Communications: Chem Comm
keyword
keyword
56108
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"