keyword
MENU ▼
Read by QxMD icon Read
search

New drug discovery

keyword
https://www.readbyqxmd.com/read/29161390/thiopental-to-desflurane-an-anaesthetic-journey-where-are-we-going-next
#1
J R Sneyd
Development targets in anaesthetic pharmacology have evolved from minimizing harm caused by unwanted effects through an era in which rapid onset and offset of drug effect were prioritised. Today's anaesthetists have access to a library of effective drugs whose characteristics offer controllable hypnosis, analgesia and paralysis with manageable off-target effects. The availability of these agents at generic prices inhibits commercial interest and this is reflected in the limited number of current anaesthetic drug development projects...
December 1, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29161011/the-design-of-plasmodium-vivax-hypoxanthine-guanine-phosphoribosyltransferase-inhibitors-as-potential-antimalarial-therapeutics
#2
Dianne T Keough, Dominik Rejman, Radek Pohl, Eva Zborníková, Dana Hockova, Tristan Croll, Michael D Edstein, Geoff W Birrell, Marina Chavchich, Lieve M J Naesens, Gregory K Pierens, Ian M Brereton, Luke W Guddat
Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) are the foremost causative agents of malaria. Due to the development of resistance to current antimalarial medications, new drugs for this parasitic disease need to be discovered. The activity of hypoxanthine-guanine-[xanthine]-phosphoribosyltransferase, HG[X]PRT, is reported to be essential for the growth of both of these parasites, making it an excellent target for antimalarial drug discovery. Here, we have used rational structure-based methods to design an inhibitor, [3R,4R]-4-guanin-9-yl-3-((S)-2-hydroxy-2-phosphonoethyl)oxy-1-N-(phosphonopropionyl)pyrrolidine, of PvHGPRT and PfHGXPRT which has Ki values of 8 nM and 7 nM, respectively for these two enzymes...
November 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29159598/etox-allies-an-automated-pipeline-for-linear-interaction-energy-based-simulations
#3
Luigi Capoferri, Marc van Dijk, Ariën S Rustenburg, Tsjerk A Wassenaar, Derk P Kooi, Eko A Rifai, Nico P E Vermeulen, Daan P Geerke
BACKGROUND: Computational methods to predict binding affinities of small ligands toward relevant biological (off-)targets are helpful in prioritizing the screening and synthesis of new drug candidates, thereby speeding up the drug discovery process. However, use of ligand-based approaches can lead to erroneous predictions when structural and dynamic features of the target substantially affect ligand binding. Free energy methods for affinity computation can include steric and electrostatic protein-ligand interactions, solvent effects, and thermal fluctuations, but often they are computationally demanding and require a high level of supervision...
November 21, 2017: Journal of Cheminformatics
https://www.readbyqxmd.com/read/29159026/highlights-for-the-6th-international-ion-channel-conference-ion-channel-structure-function-disease-and-therapeutics
#4
Limei Wang, Kewei Wang
To foster communication and interactions amongst international scholars and scientists in the field of ion channel research, the 6th International Ion Channel Conference (IICC-2017) was held between June 23-27, 2017 in the eastern coastal city of Qingdao, China. The meeting consisted of 450 attendees and 130 speakers and poster presenters. The program consisted of research progress, new findings and ongoing studies that were focused on (1) Ion channel structure and function; (2) Ion channel physiology and human diseases; (3) Ion channels as targets for drug discovery; (4) Technological advances in ion channel research...
November 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/29158600/crispr-cas9-library-screening-for-drug-target-discovery
#5
REVIEW
Morito Kurata, Kouhei Yamamoto, Branden S Moriarity, Masanobu Kitagawa, David A Largaespada
CRISPR/Cas9-based tools have rapidly developed in recent years. These include CRISPR-based gene activation (CRISPRa) or inhibition (CRISPRi), for which there are libraries. CRISPR libraries for loss of function have been widely used to identify new biological mechanisms, such as drug resistance and cell survival signals. CRISPRa is highly useful in screening for gain of functions, and CRISPRi is a more powerful tool than RNA interference (RNAi) libraries in screening for loss of functions. Positive selection using a CRISPR library can detect survival cells with specific conditions, such as drug treatment, and it can easily clarify drug resistance mechanisms...
November 20, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/29158496/diastereo-and-enantioselective-3%C3%A2-%C3%A2-3-cycloaddition-of-spirocyclopropyl-oxindoles-using-both-aldonitrones-and-ketonitrones
#6
Peng-Wei Xu, Jia-Kuan Liu, Lan Shen, Zhong-Yan Cao, Xiao-Li Zhao, Jun Yan, Jian Zhou
Optically active spirocyclic compounds play an important role in drug discovery, and new synthetic strategies for the efficient generation of spiro stereocenters are in much demand. Here we report a catalytic enantioselective cycloaddition using spirocyclic donor-acceptor cyclopropanes as a promising approach for the generation of spiro stereocenters. A diastereo- and enantioselective [3 + 3] cycloaddition of spirocyclopropyl oxindoles with both aldonitrones and ketonitrones is developed. The key to reaction development is the activation of spirocyclopropyl oxindoles by a suitable electron-withdrawing N-protecting group...
November 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/29157021/gastroparesis-pharmacotherapy-and-cardiac-risk
#7
Per M Hellström, Ahmad Al-Saffar
BACKGROUND: Gastroparesis is characterized by abnormal gastric motility and delayed emptying with symptoms of early satiety, postprandial fullness, bloating, nausea, vomiting and abdominal pain. Pharmacological discovery has been lagging because potential drugs often are associated with abnormalities of electrical conduction of the myocardium due to interaction with cardiac ion channels leading to limited pharmaceutical options for development of new drugs. OBJECTIVE: Addresses the safety of drugs for gastroparesis in terms of cardiotoxicity related to the clinical use of prokinetics and antiemetics...
November 20, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/29156384/targeting-fgfr-pathway-in-breast-cancer
#8
J Perez-Garcia, E Muñoz-Couselo, J Soberino, F Racca, J Cortes
Developments in breast cancer biology over the last years have permitted deconstructing the molecular profile of the most relevant breast cancer subtypes. This has led to an increase in therapeutic options, including more effective personalized therapy for breast cancer and substantial improvements in patient outcomes. Although currently there are only a few targeted therapies approved for metastatic breast cancer, the discovery of druggable kinase gene alterations has radically changed cancer treatment by providing novel and successfully actionable drug targets...
November 17, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/29154500/structure-activity-studies-of-peptidomimetics-based-on-kinase-inhibitory-region-of-suppressors-of-cytokine-signaling-1
#9
Sara La Manna, Laura Lopez-Sanz, Marilisa Leone, Paola Brandi, Pasqualina Liana Scognamiglio, Giancarlo Morelli, Ettore Novellino, Carmen Gomez-Guerrero, Daniela Marasco
Suppressors of Cytokine Signaling (SOCS) proteins are negative regulators of JAK proteins that are receptor-associated tyrosine kinases, which play key roles in the phosphorylation and subsequent activation of several transcription factors named STATs. Unlike the other SOCS proteins, SOCS1 and 3 show, in the N-terminal portion, a small kinase inhibitory region (KIR) involved in the inhibition of JAK kinases. Drug discovery processes of compounds based on KIR sequence demonstrated promising in functional in vitro and in inflammatory animal models and we recently developed a peptidomimetic called PS5, as lead compound...
November 20, 2017: Biopolymers
https://www.readbyqxmd.com/read/29153505/structural-basis-for-the-inhibitory-effects-of-ubistatins-in-the-ubiquitin-proteasome-pathway
#10
Mark A Nakasone, Timothy A Lewis, Olivier Walker, Anita Thakur, Wissam Mansour, Carlos A Castañeda, Jennifer L Goeckeler-Fried, Frank Parlati, Tsui-Fen Chou, Ortal Hayat, Daoning Zhang, Christina M Camara, Steven M Bonn, Urszula K Nowicka, Susan Krueger, Michael H Glickman, Jeffrey L Brodsky, Raymond J Deshaies, David Fushman
The discovery of ubistatins, small molecules that impair proteasomal degradation of proteins by directly binding to polyubiquitin, makes ubiquitin itself a potential therapeutic target. Although ubistatins have the potential for drug development and clinical applications, the lack of structural details of ubiquitin-ubistatin interactions has impeded their development. Here, we characterized a panel of new ubistatin derivatives using functional and binding assays. The structures of ubiquitin complexes with ubistatin B and hemi-ubistatin revealed direct interactions with ubiquitin's hydrophobic surface patch and the basic/polar residues surrounding it...
November 15, 2017: Structure
https://www.readbyqxmd.com/read/29152737/molecular-mechanisms-of-drug-resistance-in-ovarian-cancer
#11
REVIEW
Leyla Norouzi-Barough, Mohammad Reza Sarookhani, Mohammadreza Sharifi, Sahar Moghbelinejad, Saranaz Jangjoo, Rasoul Salehi
Ovarian cancer is the most lethal malignancy among the gynecological cancers, with a 5-year survival rate, mainly due to being diagnosed at advanced stages, recurrence and resistance to the current chemotherapeutic agents. Drug resistance is a complex phenomenon and the number of known involved genes and cross-talks between signaling pathways in this process is growing rapidly. Thus, discovering and understanding the underlying molecular mechanisms involved in chemo-resistance are crucial for management of treatment and identifying novel and effective drug targets as well as drug discovery to improve therapeutic outcomes...
November 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29152453/targeting-the-stem-cell-properties-of-adult-breast-cancer-cells-using-combinatorial-strategies-to-overcome-drug-resistance
#12
Naira V Margaryan, Elisabeth A Seftor, Richard E B Seftor, Mary J C Hendrix
Purpose of review: Cancer is a major public health problem worldwide. In aggressive cancers, which are heterogeneous in nature, there exists a paucity of targetable molecules that can be used to predict outcome and response to therapy in patients, especially those in the high risk category with a propensity to relapse following chemotherapy. This review addresses the challenges pertinent to treating aggressive cancer cells with inherent stem cell properties, with a special focus on triple-negative breast cancer (TNBC)...
September 2017: Current Molecular Biology Reports
https://www.readbyqxmd.com/read/29149813/structural-analysis-of-cd59-of-chinese-tree-shrew-a-new-reference-molecule-for-human-immune-system-specific-cd59-drug-discovery
#13
Subhamay Panda, Leena Kumari, Santamay Panda
BACKGROUND: Chinese tree shrews (Tupaia belangeri chinensis) bear several characteristics that are considered to be very crucial for utilizing in animal experimental models in biomedical research. Subsequent to the identification of key aspects and signaling pathways in nervous and immune systems, it is revealed that tree shrews acquires shared common as well as unique characteristics, and hence offers a genetic basis for employing this animal as a prospective model for biomedical research...
November 17, 2017: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/29149325/the-iuphar-bps-guide-to-pharmacology-in-2018-updates-and-expansion-to-encompass-the-new-guide-to-immunopharmacology
#14
Simon D Harding, Joanna L Sharman, Elena Faccenda, Chris Southan, Adam J Pawson, Sam Ireland, Alasdair J G Gray, Liam Bruce, Stephen P H Alexander, Stephen Anderton, Clare Bryant, Anthony P Davenport, Christian Doerig, Doriano Fabbro, Francesca Levi-Schaffer, Michael Spedding, Jamie A Davies
The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb, www.guidetopharmacology.org) and its precursor IUPHAR-DB, have captured expert-curated interactions between targets and ligands from selected papers in pharmacology and drug discovery since 2003. This resource continues to be developed in conjunction with the International Union of Basic and Clinical Pharmacology (IUPHAR) and the British Pharmacological Society (BPS). As previously described, our unique model of content selection and quality control is based on 96 target-class subcommittees comprising 512 scientists collaborating with in-house curators...
November 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29147555/what-can-machine-learning-do-for-antimicrobial-peptides-and-what-can-antimicrobial-peptides-do-for-machine-learning
#15
REVIEW
Ernest Y Lee, Michelle W Lee, Benjamin M Fulan, Andrew L Ferguson, Gerard C L Wong
Antimicrobial peptides (AMPs) are a diverse class of well-studied membrane-permeating peptides with important functions in innate host defense. In this short review, we provide a historical overview of AMPs, summarize previous applications of machine learning to AMPs, and discuss the results of our studies in the context of the latest AMP literature. Much work has been recently done in leveraging computational tools to design new AMP candidates with high therapeutic efficacies for drug-resistant infections...
December 6, 2017: Interface Focus
https://www.readbyqxmd.com/read/29147502/chemical-space-guided-discovery-of-antimicrobial-bridged-bicyclic-peptides-against-pseudomonas-aeruginosa-and-its-biofilms
#16
Ivan Di Bonaventura, Xian Jin, Ricardo Visini, Daniel Probst, Sacha Javor, Bee-Ha Gan, Gaëlle Michaud, Antonino Natalello, Silvia Maria Doglia, Thilo Köhler, Christian van Delden, Achim Stocker, Tamis Darbre, Jean-Louis Reymond
Herein we report the discovery of antimicrobial bridged bicyclic peptides (AMBPs) active against Pseudomonas aeruginosa, a highly problematic Gram negative bacterium in the hospital environment. Two of these AMBPs show strong biofilm inhibition and dispersal activity and enhance the activity of polymyxin, currently a last resort antibiotic against which resistance is emerging. To discover our AMBPs we used the concept of chemical space, which is well known in the area of small molecule drug discovery, to define a small number of test compounds for synthesis and experimental evaluation...
October 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29146472/discovery-of-the-first-low-shift-positive-allosteric-modulators-for-the-muscarinic-m1-receptor
#17
Alexander Flohr, Roman Hutter, Barbara Mueller, Claudia Bohnert, Mélanie Pellisson, Hervé Schaffhauser
Positive modulation of the muscarinic M1-receptor has for a long time attracted scientists and drug developers for the potential treatment of Alzheimer's disease or Schizophrenia. The precognitive potential of M1 activation has however not been clinically demonstrated as a result of side effects associated both with agonists and positive allosteric modulators (PAM's) of the M1-receptor. To avoid excessive activation of the M1-receptor we have designed a new screening format and developed the first low-shift positive allosteric modulators for the M1 receptor...
November 6, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29146440/clodronate-a-vesicular-atp-release-blocker
#18
REVIEW
Yoshinori Moriyama, Masatoshi Nomura
Clodronate is a first-generation bisphosphonate used worldwide for antiresorptive therapy for osteoporosis. Although clodronate is analgesic in nature, its mechanism and efficacy were unknown for some time. Recently, clodronate was identified as a selective and potent inhibitor for vesicular nucleotide transporter (VNUT), a transporter responsible for vesicular storage of ATP. Clodronate inhibits vesicular ATP release from neurons and reduces chronic neuropathic and inflammatory pain following blockade of purinergic chemical transmission...
November 13, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/29145972/cancer-immunotherapy-getting-brainy-visualizing-the-distinctive-cns-metastatic-niche-to-illuminate-therapeutic-resistance
#19
Mark Owyong, Niloufar Hosseini-Nassab, Gizem Efe, Alexander Honkala, Renske J E van den Bijgaart, Vicki Plaks, Bryan Ronain Smith
The advent of cancer immunotherapy (CIT) and its success in treating primary and metastatic cancer may offer substantially improved outcomes for patients. Despite recent advancements, many malignancies remain resistant to CIT, among which are brain metastases, a particularly virulent disease with no apparent cure. The immunologically unique niche of the brain has prompted compelling new questions in immuno-oncology such as the effects of tissue-specific differences in immune response, heterogeneity between primary tumors and distant metastases, and the role of spatiotemporal dynamics in shaping an effective anti-tumor immune response...
November 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/29145743/novel-avenues-for-drug-discovery-in-diabetic-kidney-disease
#20
Matthew D Breyer, Matthias Kretzler
Diabetic kidney disease (DKD) has emerged as major cause of morbidity and mortality. After progressing to renal failure, over 70% of DKD patients are dead with five years. New treatments to slow this progression are desperately needed. Areas covered: This review highlights the current treatment options for people with DKD with a particular focus on angiotensin pathway blockade and the potential use of sodium glucose linked transporter 2 (SGLT2) inhibitors. These treatments are associated with an initial decrease in glomerular filtration rate (GFR) and albuminuria; there is also attention on renal hyperfiltration as therapeutic target...
November 16, 2017: Expert Opinion on Drug Discovery
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"