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https://www.readbyqxmd.com/read/27905163/fungal-glycolipid-hydrolase-inhibitors-and-their-effect-on-cryptococcus-neoformans
#1
Andres Gonzalez Santana, Christina Tysoe, Guanggan Hu, James Kronstad, Ethan Goddard-Borger, Stephen Withers
Pathogenic fungi kill an estimated 1.3 million people each year. This number is predicted to rise as drug resistance spreads, thus antifungal drugs with novel modes of action are urgently required. Fungal endoglycoceramidase-related proteins 1 and 2 (EGCrP-1 and -2), which hydrolyse glucosylceramide and ergosteryl beta-glucoside, respectively, are important for fungal cell growth and have been identified as potential targets for drug development. A library of iminosugar derivatives was screened against EGCrP-1 and -2, thereby identifying a number of competitive inhibitors with nanomolar affinities...
November 30, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27904831/orphan-drug-development-in-china-turning-challenges-into-opportunities
#2
Xiaowei Jin, Li Chen
Of over 7,000 known rare diseases, only 5% currently have an available treatment option worldwide. Moreover, the vast majority of rare disease patients in China have no access to treatment due to limited availability and the lack of appropriate infrastructure in China's healthcare system. Despite increased interest in orphan drug development, drug companies in China with active programs on drugs to treat rare diseases are still limited. Hence, there is a huge unmet need in China, with over 10 million patients suffering from rare diseases...
November 2016: Intractable & Rare Diseases Research
https://www.readbyqxmd.com/read/27904804/mining-snps-in-extracellular-vesicular-transcriptome-of-trypanosoma-cruzi-a-step-closer-to-early-diagnosis-of-neglected-chagas-disease
#3
Pallavi Gaur, Anoop Chaturvedi
One of the newest and strongest members of intercellular communicators, the Extracellular vesicles (EVs) and their enclosed RNAs; Extracellular RNAs (exRNAs) have been acknowledged as putative biomarkers and therapeutic targets for various diseases. Although a very deep insight has not been possible into the physiology of these vesicles, they are believed to be involved in cell-to-cell communication and host-pathogen interactions. EVs might be significantly helpful in discovering biomarkers for possible target identification as well as prognostics, diagnostics and developing vaccines...
2016: PeerJ
https://www.readbyqxmd.com/read/27904297/the-push-for-additional-orphan-drugs-can-the-fda-do-more-to-encourage-their-development
#4
Stephen Barlas
Can the FDA do more to encourage orphan drug development?
November 2016: P & T: a Peer-reviewed Journal for Formulary Management
https://www.readbyqxmd.com/read/27904006/translational-science-in-drug-development-challenges-and-possible-solutions
#5
Shyh Yuh Liou, Susumu Nakade
No abstract text is available yet for this article.
2016: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/27902767/towards-a-non-human-primate-model-of-alpha-synucleinopathy-for-development-of-therapeutics-for-parkinson-s-disease-optimization-of-aav1-2-delivery-parameters-to-drive-sustained-expression-of-alpha-synuclein-and-dopaminergic-degeneration-in-macaque
#6
James B Koprich, Tom H Johnston, Gabriela Reyes, Vanessa Omana, Jonathan M Brotchie
Recent failures in clinical trials for disease modification in Parkinson's disease have highlighted the need for a non-human primate model of the synucleinopathy underpinning dopaminergic neuron degeneration. The present study was defined to begin the development of such a model in cynomolgus macaque. We have validated surgical and vector parameters to define a means to provide a robust over-expression of alpha-synuclein which is associated with Lewy-like pathology and robust degeneration of the nigrostriatal pathway...
2016: PloS One
https://www.readbyqxmd.com/read/27902735/role-of-hepatic-specific-transcription-factors-and-polycomb-repressive-complex-2-during-induction-of-fibroblasts-to-hepatic-fate
#7
Shima Rastegar-Pouyani, Niusha Khazaei, Ping Wee, Abdulshakour Mohammadnia, Moein Yaqubi
Direct reprogramming using defined sets of transcription factors (TFs) is a recent strategy for generating induced hepatocytes (iHeps) from fibroblasts for use in regenerative medicine and drug development. Comprehensive studies detailing the regulatory role of TFs during this reprogramming process could help increase its efficiency. This study aimed to find the TFs with the greatest influences on the generation of iHeps from fibroblasts, and to further understand their roles in the regulation of the gene expression program...
2016: PloS One
https://www.readbyqxmd.com/read/27901159/a-portable-and-reconfigurable-multi-organ-platform-for-drug-development-with-onboard-microfluidic-flow-control
#8
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/27900885/selecting-heart-failure-patients-for-metabolic-interventions
#9
Harmen G Booij, Anne M Koning, Harry van Goor, Rudolf A de Boer, B Daan Westenbrink
Introduction Heart failure (HF) has become the cardiovascular epidemic of the century and now imposes an immense burden on health care systems. While our understanding of the pathophysiology of HF has increased dramatically, the translation of knowledge into clinical practice has been disappointing. Metabolic dysfunction in HF has been studied for eight decades, but these efforts have not resulted in effective therapies. This paucity in clinical translation probably results from the variable contribution of metabolic dysfunction to the underlying heart disease...
November 30, 2016: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/27900781/the-present-and-future-of-opioid-analgesics-in-small-animal-practice
#10
REVIEW
B T Simon, P V Steagall
Opioids are the cornerstone for the treatment of acute pain in small animal patients. This is primarily because of their remarkable safety profile, high efficacy, and benefit of reversibility. There have been some significant advances in our knowledge on opioid pharmacology and clinical usage in companion animal medicine. This review discusses the progression of opioid use in small animal practice providing current misconceptions and controversies in light of routes of administration. Potential targets for research and drug development and novel therapies are discussed in addition to the concepts of glial cell modulators, individual variability, and opioid tolerance and hyperalgesia...
November 30, 2016: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27900209/i-spy-2-optimising-cancer-drug-development-in-the-21st-century
#11
EDITORIAL
Rupert Bartsch, Evandro de Azambuja
No abstract text is available yet for this article.
2016: ESMO Open
https://www.readbyqxmd.com/read/27899803/novel-targets-in-the-treatment-of-chronic-graft-versus-host-disease
#12
REVIEW
A Im, F T Hakim, S Z Pavletic
Despite advances that have improved survival after allogeneic hematopoietic stem cell transplantation (HCT), chronic graft-versus-host disease (GVHD) remains a leading cause of late morbidity and mortality after transplant. Current treatment options show limited efficacy in steroid-refractory disease, and there exists a paucity of robust data to guide management decisions. Lack of United States Food and Drug Administration (FDA) or European Medicines Agency (EMA) approved agents in GVHD underscore the importance of developing novel therapies...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27899793/bacterial-proteases-untapped-antimicrobial-drug-targets
#13
REVIEW
Elizabeth Culp, Gerard D Wright
Bacterial proteases are an extensive collection of enzymes that have vital roles in cell viability, stress response and pathogenicity. Although their perturbation clearly offers the potential for antimicrobial drug development, both as traditional antibiotics and anti-virulence drugs, they are not yet the target of any clinically used therapeutics. Here we describe the potential for and recent progress in the development of compounds targeting bacterial proteases with a focus on AAA+ family proteolytic complexes and signal peptidases (SPs)...
November 30, 2016: Journal of Antibiotics
https://www.readbyqxmd.com/read/27898041/ribosome-inactivating-proteins-from-plants-a-historical-overview
#14
REVIEW
Andrea Bolognesi, Massimo Bortolotti, Stefania Maiello, Maria Giulia Battelli, Letizia Polito
This review provides a historical overview of the research on plant ribosome-inactivating proteins (RIPs), starting from the first studies at the end of eighteenth century involving the purification of abrin and ricin, as well as the immunological experiments of Paul Erlich. Interest in these plant toxins was revived in 1970 by the observation of their anticancer activity, which has given rise to a large amount of research contributing to the development of various scientific fields. Biochemistry analyses succeeded in identifying the enzymatic activity of RIPs and allowed for a better understanding of the ribosomal machinery...
November 26, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27898018/combating-ebola-with-repurposed-therapeutics-using-the-cando-platform
#15
Gaurav Chopra, Sashank Kaushik, Peter L Elkin, Ram Samudrala
Ebola virus disease (EVD) is extremely virulent with an estimated mortality rate of up to 90%. However, the state-of-the-art treatment for EVD is limited to quarantine and supportive care. The 2014 Ebola epidemic in West Africa, the largest in history, is believed to have caused more than 11,000 fatalities. The countries worst affected are also among the poorest in the world. Given the complexities, time, and resources required for a novel drug development, finding efficient drug discovery pathways is going to be crucial in the fight against future outbreaks...
November 25, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27896754/application-of-multiplex-biomarker-approaches-to-accelerate-drug-discovery-and-development
#16
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/27896627/n-11-c-methyl-amd3465-pet-as-a-tool-for-in-vivo-measurement-of-chemokine-receptor-4-cxcr4-occupancy-by-therapeutic-drugs
#17
S V Hartimath, M A Khayum, A van Waarde, R A J O Dierckx, E F J de Vries
PURPOSE: Chemokine receptor 4 (CXCR4) is overexpressed in many cancers and a potential drug target. We have recently developed the tracer N-[(11)C]methyl-AMD3465 for imaging of CXCR4 expression by positron emission tomography (PET). We investigated the pharmacokinetics of N-[(11)C]methyl-AMD3465 in rats bearing a C6 tumor and assessed whether the CXCR4 occupancy by the drug Plerixafor® can be measured with this PET tracer. PROCEDURE: A subcutaneous C6 tumor was grown in Wistar rats...
November 28, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/27895553/glypican-6-enhances-n-methyl-d-aspartate-receptor-function-in-human-induced-pluripotent-stem-cell-derived-neurons
#18
Kaoru Sato, Kanako Takahashi, Yukari Shigemoto-Mogami, Kaori Chujo, Yuko Sekino
The in vitro use of neurons that are differentiated from human induced pluripotent stem cells (hiPSC-neurons) is expected to improve the prediction accuracy of preclinical tests for both screening and safety assessments in drug development. To achieve this goal, hiPSC neurons are required to differentiate into functional neurons that form excitatory networks and stably express N-methyl-D-aspartate receptors (NMDARs). Recent studies have identified some astrocyte-derived factors that are important for the functional maturation of neurons...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27895328/regulatory-watch-challenges-in-drug-development-for-central-nervous-system-disorders-a-european-medicines-agency-perspective
#19
Florence Butlen-Ducuing, Frank Pétavy, Lorenzo Guizzaro, Malgorzata Zienowicz, Manuel Haas, Enrica Alteri, Tomas Salmonson, Emmanuelle Corruble
No abstract text is available yet for this article.
November 29, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27895269/stability-of-dihydroartemisinin-piperaquine-tablet-halves-during-prolonged-storage-under-tropical-conditions
#20
Eva Maria Hodel, Harparkash Kaur, Dianne J Terlouw
Dihydroartemisinin-piperaquine (DP) is recommended for the treatment of uncomplicated malaria, used in efforts to contain artemisinin resistance, and increasingly considered for mass drug administration. Because of the narrow therapeutic dose range and available tablet strengths, the manufacturers and World Health Organization recommended regimens involve breaking tablets into halves to accurately dose children according to body weight. Use of tablet fractions in programmatic settings under tropical conditions requires a highly stable product; however, the stability of DP tablet fractions is unknown...
November 28, 2016: American Journal of Tropical Medicine and Hygiene
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