Read by QxMD icon Read

Trends in Pharmacological Sciences

Graeme Milligan, Asuka Inoue
Rapid developments in genome editing, based largely on CRISPR/Cas9 technologies, are offering unprecedented opportunities to eliminate the expression of single or multiple gene products in intact organisms and in model cell systems. Elimination of individual G protein-coupled receptors (GPCRs), both single and multiple G protein subunits, and arrestin adaptor proteins is providing new and sometimes unanticipated insights into molecular details of the regulation of cell signalling pathways and the behaviour of receptor ligands...
March 13, 2018: Trends in Pharmacological Sciences
Sarah J Trenfield, Atheer Awad, Alvaro Goyanes, Simon Gaisford, Abdul W Basit
3D printing (3DP) is forecast to be a highly revolutionary technology within the pharmaceutical sector. In particular, the main benefits of 3DP lie in the production of small batches of medicines, each with tailored dosages, shapes, sizes and release characteristics. The manufacture of medicines in this way may finally lead to the concept of personalised medicines becoming a reality. In the shorter term, 3DP could be extended throughout the drug development process, ranging from preclinical development and clinical trials, through to frontline medical care...
March 10, 2018: Trends in Pharmacological Sciences
Bindu D Paul, Juan I Sbodio, Solomon H Snyder
Besides its essential role in protein synthesis, cysteine plays vital roles in redox homeostasis, being a component of the major antioxidant glutathione (GSH) and a potent antioxidant by itself. In addition, cysteine undergoes a variety of post-translational modifications that modulate several physiological processes. It is becoming increasingly clear that redox-modulated events play important roles not only in peripheral tissues but also in the brain where cysteine disposition is central to these pathways...
March 9, 2018: Trends in Pharmacological Sciences
Agata Bielecka-Dabrowa, Jarosław Fabis, Dimitri P Mikhailidis, Stephan von Haehling, Amirhossein Sahebkar, Jacek Rysz, Maciej Banach
Some studies using small doses of statins revealed significant benefits for patients with chronic heart failure (HF). However, the results of large randomized studies did not confirm these advantages. Along with the primary effect of cholesterol lowering, statins have many ancillary actions that may be relevant for body wasting. In this context, the fear of muscle-related side effects needs to be put into clinical context and assessed appropriately before statins are either withheld or withdrawn in patients with sarcopenia (muscle wasting)...
March 1, 2018: Trends in Pharmacological Sciences
S Stevens Negus
The opioid crisis has stimulated renewed interest in analgesic drug development. This effort will involve preclinical-to-clinical translational research and will benefit from a focus on endpoints that are both clinically relevant and shared across laboratory animals and humans. Measures of pain-related functional impairment and behavioral depression could serve this purpose.
February 28, 2018: Trends in Pharmacological Sciences
Giovanni Musso, Roberto Gambino, Maurizio Cassader, Elena Paschetta, Antonio Sircana
The resolution of necroinflammation and fibrosis remains a primary clinical target in nonalcoholic steatohepatitis (NASH), the most common chronic liver disease and a major cause of end-stage liver disease. Our understanding of the basic molecular mechanisms driving inflammation and fibrosis and their resolution in obesity-related conditions, including NASH, have led to the proposal of a novel, tractable therapeutic paradigm involving specialized proresolving mediators (SPMs), namely lipoxins (LXs), resolvins (Rvs), protectins (PDs), and maresins (MaRs)...
February 27, 2018: Trends in Pharmacological Sciences
Eduardo N Chini, Claudia C S Chini, Jair Machado Espindola Netto, Guilherme C de Oliveira, Wim van Schooten
Recent reports indicate that intracellular NAD levels decline in tissues during chronological aging, and that therapies aimed at increasing cellular NAD levels could have beneficial effects in many age-related diseases. The protein CD38 (cluster of differentiation 38) is a multifunctional enzyme that degrades NAD and modulates cellular NAD homeostasis. At the physiological level, CD38 has been implicated in the regulation of metabolism and in the pathogenesis of multiple conditions including aging, obesity, diabetes, heart disease, asthma, and inflammation...
February 23, 2018: Trends in Pharmacological Sciences
Juliana Pereira Lopes Gonçalves, Daniel Palmer, Morten Meldal
The melanocortin-4 receptor (MC4R) regulates adipose tissue formation and energy homeostasis, and is believed to be a monogenic target for novel antiobesity therapeutics. Several research efforts targeting this receptor have identified potent and selective agonists. While viable agonists have been characterized in vitro, undesirable side effects frequently appeared during clinical trials. The most promising candidates have diverse structures, including linear peptides, cyclic peptides, and small molecules. Herein, we present a compilation of potent MC4R agonists and discuss the pivotal structural differences within those molecules that resulted in good selectivity for MC4R over other melanocortins...
February 22, 2018: Trends in Pharmacological Sciences
Nadine Kabbani, Robert A Nichols
The α7 nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel (LGIC) that plays an important role in cellular calcium signaling and contributes to several neurological diseases. Agonist binding to the α7 nAChR induces fast channel activation followed by inactivation and prolonged desensitization while triggering long-lasting calcium signaling. These activities foster neurotransmitter release, synaptic plasticity, and somatodendritic regulation in the brain. We discuss here the ability of α7 nAChRs to operate in ionotropic (α7 i ) and metabotropic (α7 m ) modes, leading to calcium-induced calcium release (CICR) and G protein-associated inositol trisphosphate (IP 3 )-induced calcium release (IICR), respectively...
February 7, 2018: Trends in Pharmacological Sciences
Wenjing Wang, Yuhui Qiao, Zijian Li
In classical G-protein-coupled receptor (GPCR) activation, GPCRs couple to a variety of heterotrimeric G proteins on the membrane and then activate downstream signaling pathways. More recently, GPCRs have been found to couple to different effector proteins, including different G protein subtypes and regulatory proteins, such as arrestins. Some novel modes of GPCR activation have been proposed to explain their complex behaviors. In this review, we summarize the main novel modes of GPCR activation, including biased activation, intracellular activation, dimerization activation, transactivation, and biphasic activation...
January 30, 2018: Trends in Pharmacological Sciences
Yang Yang, Malgorzata A Mis, Mark Estacion, Sulayman D Dib-Hajj, Stephen G Waxman
Chronic pain is a global unmet medical need. Most existing treatments are only partially effective or have side effects that limit their use. Rapid progress in elucidating the contribution of specific genes, including those that encode peripheral voltage-gated sodium channels, to the pathobiology of chronic pain suggests that it may be possible to advance pain pharmacotherapy. Focusing on voltage-gated sodium channel NaV1.7 as an example, this article reviews recent progress in developing patient-specific induced pluripotent stem cells (iPSCs) and their differentiation into sensory neurons, together with advances in structural modeling, that have provided a basis for first-in-human translational studies...
January 19, 2018: Trends in Pharmacological Sciences
Igor Kissin
The different stages of the life cycle of a drug - 'prenatal' stage, birth of a drug, rapid growth, maturity and stability, decline, and status before 'death' - are reflected in the three following databases: journal articles (; patents (US Patent Office-; and approved drugs (FDA - These databases are huge, from authoritative sources, correctly classified, and they properly link different datasets...
January 18, 2018: Trends in Pharmacological Sciences
Rodney Rouse, Issam Zineh, David G Strauss
Translational science refers to translating basic scientific findings to practical application (i.e., 'bench-to-bedside'). An underappreciated aspect of translational science is regulatory science. Herein, we focus on the importance of regulatory science to facilitate development of innovative new drugs and optimize use of approved drugs, with a call for community participation.
January 9, 2018: Trends in Pharmacological Sciences
Feng Zhu, Xiao Xu Li, Sheng Yong Yang, Yu Zong Chen
The selection of the right drug targets is critically important for the successful and cost-effective development and clinical testing of drugs. A 2009 paper reported an in silico prospective prediction of the clinical potential of 156 targets of clinical trial drugs (all of these targets were without an approved drug at the time of the paper's publication). Eight years later, the assessment of the clinical status of these targets revealed impressive capability of the in silico method in prospectively predicting the clinical success of drug targets...
December 30, 2017: Trends in Pharmacological Sciences
Nshunge Musheshe, Martina Schmidt, Manuela Zaccolo
How cAMP generates hormone-specific effects has been debated for many decades. Fluorescence resonance energy transfer (FRET)-based sensors for cAMP allow real-time imaging of the second messenger in intact cells with high spatiotemporal resolution. This technology has made it possible to directly demonstrate that cAMP signals are compartmentalised. The details of such signal compartmentalisation are still being uncovered, and recent findings reveal a previously unsuspected submicroscopic heterogeneity of intracellular cAMP...
December 27, 2017: Trends in Pharmacological Sciences
Matthew Hearing, Nicholas Graziane, Yan Dong, Mark J Thomas
Commonalities in addictive behavior, such as craving, stimuli-driven drug seeking, and a high propensity for relapse following abstinence, have pushed for a unified theory of addiction that encompasses most abused substances. This unitary theory has recently been challenged - citing distinctions in structural neural plasticity, biochemical signaling, and neural circuitry to argue that addiction to opioids and psychostimulants is behaviorally and neurobiologically distinct. Recent more selective examination of drug-induced plasticity has highlighted that these two drug classes promote an overall reward circuitry signaling overlap through modifying excitatory synapses in the nucleus accumbens - a key constituent of the reward system...
March 2018: Trends in Pharmacological Sciences
Ivana Vancurova, Mohammad M Uddin, Yue Zou, Ales Vancura
The rationale for developing histone deacetylase (HDAC) inhibitors (HDACi) as anticancer agents was based on their ability to induce apoptosis and cell cycle arrest in cancer cells. However, while HDACi have been remarkably effective in the treatment of hematological malignancies, clinical studies with HDACi as single agents in solid cancers have been disappointing. Recent studies have shown that, in addition to inducing apoptosis in cancer cells, class I HDACi induce IκB kinase (IKK)-dependent expression of proinflammatory chemokines, such as interleukin-8 (IL8; CXCL8), resulting in the increased proliferation of tumor cells, and limiting the effectiveness of HDACi in solid tumors...
March 2018: Trends in Pharmacological Sciences
(no author information available yet)
No abstract text is available yet for this article.
February 2018: Trends in Pharmacological Sciences
Kelsie Eichel, Mark von Zastrow
G protein-coupled receptors (GPCRs) comprise a large and diverse class of signal-transducing receptors that undergo dynamic and isoform-specific membrane trafficking. GPCRs thus have an inherent potential to initiate or regulate signaling reactions from multiple membrane locations. This review discusses emerging insights into the subcellular organization of GPCR function in mammalian cells, focusing on signaling transduced by heterotrimeric G proteins and β-arrestins. We summarize recent evidence indicating that GPCR-mediated activation of G proteins occurs not only from the plasma membrane (PM) but also from endosomes and Golgi membranes and that β-arrestin-dependent signaling can be transduced from the PM by β-arrestin trafficking to clathrin-coated pits (CCPs) after dissociation from a ligand-activated GPCR...
February 2018: Trends in Pharmacological Sciences
Michael Kauk, Carsten Hoffmann
Within the past decade, a large increase in structural knowledge from crystallographic studies has significantly fostered our understanding of the structural biology of G protein-coupled receptors (GPCRs). However, information on dynamic events upon receptor activation or deactivation is not yet readily accessed by these structural approaches. GPCR-based fluorescence resonance energy transfer or bioluminescence resonance energy transfer sensors or sensors for interacting proteins (e.g., G proteins or arrestins) can in part cover this gap...
February 2018: Trends in Pharmacological Sciences
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"