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Trends in Pharmacological Sciences

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https://www.readbyqxmd.com/read/30384981/a2ar-d2r-heteroreceptor-complexes-in-cocaine-reward-and-addiction
#1
REVIEW
Dasiel O Borroto-Escuela, Karolina Wydra, Malgorzata Filip, Kjell Fuxe
The concept of allosteric receptor-receptor interactions in G protein-coupled receptor homo- and heteroreceptor complexes in which they physically interact provides a new dimension to molecular integration in the brain. The receptor-receptor interactions dynamically change recognition, pharmacology, signaling, and trafficking of the participating receptors. Among the receptor complexes, disruption of the A2A receptor-dopamine D2 receptor (A2AR-D2R) complex by an A2AR agonist has been shown to fully block the inhibition of cocaine self-administration...
October 29, 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/30376967/pharmaceutical-cocrystal-drug-products-an-outlook-on-product-development
#2
REVIEW
Rahamatullah Shaikh, Ravendra Singh, Gavin M Walker, Denise M Croker
Active pharmaceutical ingredients (APIs) are most commonly formulated and delivered to patients in the solid state. Recently, an alternative API solid-state form, namely the pharmaceutical cocrystal, has witnessed increasing academic and industrial interest due to its potential to deliver bespoke physical properties in the pharmaceutical drug product. This interest has been supported by advances in cocrystal discovery, development, and approval, enabled primarily by a supportive new FDA guidance in February 2018...
October 27, 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/30352697/copper-and-zinc-dysregulation-in-alzheimer-s-disease
#3
REVIEW
Stefano L Sensi, Alberto Granzotto, Mariacristina Siotto, Rosanna Squitti
Alzheimer's disease (AD) is one of the most common forms of dementia. Despite a wealth of knowledge on the molecular mechanisms involved in AD, current treatments have mainly focused on targeting amyloid β (Aβ) production, but have failed to show significant effects and efficacy. Therefore, a critical reconsideration of the multifactorial nature of the disease is needed. AD is a complex multifactorial disorder in which, along with Aβ and tau, the convergence of polygenic, epigenetic, environmental, vascular, and metabolic factors increases the global susceptibility to the disease and shapes its course...
October 20, 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/30327127/orphan-drugs-and-their-impact-on-pharmaceutical-development-trends-in-pharmacological-sciences-39-525-535-2018
#4
Misty M Attwood, Mathias Rask-Andersen, Helgi B Schiöth
No abstract text is available yet for this article.
October 13, 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/30292585/purinergic-signaling-a-new-pharmacological-target-against-viruses
#5
REVIEW
Davide Ferrari, Marco Idzko, Tobias Müller, Roberto Manservigi, Peggy Marconi
Viral diseases represent a major global problem in human health, with high morbidity and mortality. Despite recent progress in antiviral treatments, several viral diseases are still not controlled and millions suffer from them every year. It has recently emerged that purinergic signaling participates in viral infection and replication. Furthermore, stimulation of purinergic receptors in infected cells also induces inflammatory and antiviral responses, thus contributing to the host antiviral defense. Here we review the multiple roles played by the purinergic signaling network in cell-virus interactions that can lead either to viral maintenance in the cells or, by contrast, to stronger antiviral responses, and discuss potential future applications of purinergic signaling modulation for the treatment of viral diseases...
October 3, 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/30282590/precision-medicine-through-antisense-oligonucleotide-mediated-exon-skipping
#6
REVIEW
Dunhui Li, Frank L Mastaglia, Sue Fletcher, Steve D Wilton
Clinical implementation of two recently approved antisense RNA therapeutics - Exondys51® to treat Duchenne muscular dystrophy (Duchenne MD) and Spinraza® as a treatment for spinal muscular atrophy (SMA) - highlights the therapeutic potential of antisense oligonucleotides (ASOs). As shown in the Duchenne and Becker cases, the identification and specific removal of 'dispensable' exons by exon-skipping ASOs could potentially bypass lethal mutations in other genes and bring clinical benefits to affected individuals carrying amenable mutations...
September 30, 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/30279003/refining-early-antitumoral-drug-development
#7
Alberto Ocaña, Sara García-Alonso, Eitan Amir, Atanasio Pandiella
The failure rate of development of new drugs in oncology is high, with up to 95% of drugs tested in Phase I not reaching the market. Causes behind this high failure rate are discussed here, and solutions to increase the success in the development of antitumor drugs are suggested.
September 29, 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/30268571/natural-products-as-a-source-for-antifibrosis-therapy
#8
REVIEW
Dan-Qian Chen, Ya-Long Feng, Gang Cao, Ying-Yong Zhao
Although fibrosis is a final pathological feature of many chronic diseases, few interventions are available that specifically target the pathogenesis of fibrosis. Natural products are becoming increasingly recognized as effective therapies for fibrosis. The highlights of common cellular and molecular mechanisms of fibrosis facilitate the discovery of effective antifibrotic drugs. We describe some new profibrotic mechanisms and corresponding therapeutic targets using natural products. Interleukin, ephrin-B2, Gas6/TAM, Wnt/β-catenin, hedgehog pathway, PPARγ, lysophosphatidic acid, and CTGF are promising therapeutic targets...
September 26, 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/30213439/pulmonary-ionocytes-challenge-the-paradigm-in-cystic-fibrosis
#9
Finn J Hawkins, Darrell N Kotton
Two recent studies have identified novel airway cells termed pulmonary ionocytes that express higher levels of CFTR than other airway cells express. These findings raise new questions in the evolving debate about the physiological role of CFTR in lung epithelia and its importance in the pathogenesis of cystic fibrosis (CF).
September 10, 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/30201270/kill-em-all-efgartigimod-immunotherapy-for-autoimmune-diseases
#10
Jagadeesh Bayry, Srini V Kaveri
Neonatal Fc receptors (FcRns) recycle IgGs by preventing their lysosome degradation. As this process also enhances half-life of pathogenic auto-IgG, inspired from the mechanisms of intravenous immunoglobulin, several inhibitors of IgG-FcRn interface have been conceived for treating autoimmune diseases. Among them, the high-affinity FcRn-binding engineered Fc molecule efgartigimod has recently completed phase I clinical trial.
September 7, 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/30196936/the-who-what-and-why-of-drug-discovery-and-development
#11
Glenn Hogan, Mark Tangney
Inquiry into declining pharmaceutical R&D efficiency has focussed on 'what' can be improved, with only brief thought given to 'who' can be improved. Here, we argue that enabling people in the idea-to-product chain to have a more holistic knowledge of the behaviours and incentives of each other can optimise R&D.
September 6, 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/30180973/therapeutic-targeting-of-endosomal-g-protein-coupled-receptors
#12
REVIEW
Alex R B Thomsen, Dane D Jensen, Gareth A Hicks, Nigel W Bunnett
G-protein-coupled receptors (GPCRs) are conventionally considered to function at the plasma membrane, where they detect extracellular ligands and activate heterotrimeric G proteins that transmit intracellular signals. Consequently, drug discovery efforts have focused on identification of agonists and antagonists of cell surface GPCRs. However, β-arrestin (ARR)-dependent desensitization and endocytosis rapidly terminate G protein signaling at the plasma membrane. Emerging evidence indicates that GPCRs can continue to signal from endosomes by G-protein- and βARR-dependent processes...
September 1, 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/30144949/ribonucleases-as-drug-targets
#13
REVIEW
Emanuele Canestrari, Zain Paroo
Across disease indications, there is immediate need for new drug targets. Target scarcity is reflected in a growing number of same-target drugs of marginal clinical value. Advances in RNA mechanisms of disease are revealing a windfall of targets for nucleic acids therapeutics. However, nucleic acids remain limited as pharmaceutical agents. Because enzymes are predominant drug targets, ribonucleases represent an established target class to capitalize on RNA mechanisms of disease. Analysis of the human proteome identified 122 ribonucleases...
August 22, 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/30343728/-crystal-clear-lysophospholipid-receptor-structure-insights-and-controversies
#14
REVIEW
Victoria A Blaho, Jerold Chun
Lysophospholipids (LPLs), particularly sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA), are bioactive lipid modulators of cellular homeostasis and pathology. The discovery and characterization of five S1P- and six LPA-specific G protein-coupled receptors (GPCRs), S1P1-5 and LPA1-6 , have expanded their known involvement in all mammalian physiological systems. Resolution of the S1P1 , LPA1 , and LPA6 crystal structures has fueled the growing interest in these receptors and their ligands as targets for pharmacological manipulation...
November 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/30343727/abuse-potential-of-biased-mu-opioid-receptor-agonists
#15
S Stevens Negus, Kevin B Freeman
G protein-biased mu opioid receptor (GPB-MOR) agonists constitute an emerging class of opioid analgesics. The first-in-class GPB-MOR agonist TRV130 (oliceridine) produces typical opioid-like abuse-related effects in rodents and humans. Although GPB-MOR agonists may be safer than conventional opioids on some endpoints, prevailing evidence suggests that they will retain opioid-like abuse potential.
November 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/30343726/science-based-actions-can-help-address-the-opioid-crisis
#16
David H Epstein, Markus Heilig, Yavin Shaham
The epidemic of addiction and overdose is real. Addiction among pain patients accounts for only a small proportion but a large number. Scientific opinion leaders can be most effective on two fronts, each relatively low-tech: dissemination and oversight of empirically established treatments, and promulgation of social-science-based strategies for population-level prevention.
November 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/30343725/immunopharmacotherapies-for-treating-opioid-use-disorder
#17
Matthew L Banks, Margaret E Olson, Kim D Janda
The current opioid crisis has reinvigorated interest in the development of therapeutics for opioid use disorder (OUD), and the choice of preclinical translational endpoints is an essential consideration. Antiopioid immunopharmacotherapies (e.g., conjugate vaccines) that sequester drug peripherally, preventing opioids from reaching targeted receptors in the brain, have recently emerged as promising therapeutics.
November 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/30249403/micrornas-novel-molecular-targets-and-response-modulators-of-statin-therapy
#18
REVIEW
Mohammad Mohajeri, Maciej Banach, Stephen L Atkin, Alexandra E Butler, Massimiliano Ruscica, Gerald F Watts, Amirhossein Sahebkar
Cardiovascular disease (CVD) is a major cause of death globally. Addressing cardiovascular risk factors, particularly dyslipidemia, represents the most robust clinical strategy towards reducing the CVD burden. Statins inhibit 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and represent the main therapeutic approach for lowering cholesterol and reducing plaque formation/rupture. The protective effects of statins extend beyond lowering cholesterol. MicroRNAs (miRNAs or miRs), small noncoding regulatory RNAs, likely mediate the positive pleiotropic effects of statins via modulation of lipid metabolism, enhancement of endothelial function, inhibition of inflammation, improvement of plaque stability, and immune regulation...
November 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/30150001/metformin-as-an-anticancer-agent
#19
REVIEW
Ales Vancura, Pengli Bu, Madhura Bhagwat, Joey Zeng, Ivana Vancurova
Metformin has been a frontline therapy for type 2 diabetes (T2D) for many years. Its effectiveness in T2D treatment is mostly attributed to its suppression of hepatic gluconeogenesis; however, the mechanistic aspects of metformin action remain elusive. In addition to its glucose-lowering effect, metformin possesses other pleiotropic health-promoting effects that include reduced cancer risk and tumorigenesis. Metformin inhibits the electron transport chain (ETC) and ATP synthesis; however, recent data reveal that metformin regulates AMP-activated protein kinase (AMPK) and the mechanistic target of rapamycin complex 1 (mTORC1) by multiple, mutually nonexclusive mechanisms that do not necessarily depend on the inhibition of ETC and the cellular ATP level...
October 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/30143244/targeting-fcrn-to-generate-antibody-based-therapeutics
#20
REVIEW
E Sally Ward, Raimund J Ober
The MHC class I-related receptor FcRn serves multiple roles ranging from the regulation of levels of IgG isotype antibodies and albumin throughout the body to the delivery of antigen into antigen loading compartments in specialized antigen-presenting cells. In parallel with studies directed towards understanding FcRn at the molecular and cellular levels, there has been an enormous expansion in the development of engineering strategies involving FcRn to modulate the dynamic behavior of antibodies, antigens, and albumin...
October 2018: Trends in Pharmacological Sciences
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