Showing papers in "Trends in Pharmacological Sciences in 2015"

TL;DR: All approved small-molecule kinase inhibitors with an emphasis on binding mechanism and structural features are presented, current challenges are summarized, and future directions in this field are discussed.

TL;DR: Secretion of adipokines, including leptin, adiponectin, fibroblast growth factor 21, retinol-binding protein 4 (RBP4), dipeptidyl peptidase 4 (DPP-4), bone morphogenetic protein (BMP)-4, BMP-7, vaspin, apelin, and progranulin, is altered in adipose tissue dysfunction and may contribute to a spectrum of obesity-associated diseases.

TL;DR: The state of the art of critical eCB functions in peripheral organs is reviewed to establish consensus views on the relevance of the peripheral ECS for human health and disease pathogenesis, as well as highlighting emerging challenges and therapeutic hopes.

TL;DR: This review presents some evidence to show that the docking might be questionable, despite a high score, in some cases, and some cases the accuracy of docking can even change from 0% to 92.66%.

TL;DR: Amyloid biomarkers will be of special value in the clinic to identify patients with brain amyloid deposition at risk for progression to AD dementia, to enable initiation of treatment before neurodegeneration is too severe, and to monitor drug effects on Aβ metabolism or pathology to guide dosage.

TL;DR: The functional makeup and expression of the nAChRs in mammalian brain, and their role as targets in neurodegenerative diseases, neurodevelopmental disorders, and neuropathic pain are discussed.

TL;DR: This work reviews the generic residue numbering schemes for each GPCR class, as well as a complementary structure-based scheme, and provides illustrative examples and G PCR database (GPCRDB) web tools to number any receptor sequence or structure.

TL;DR: Current literature suggests that modulating chemokine signaling, especially CCL2/CCR2, may be beneficial in TBI treatment, and attempts to modulate these pathways for therapeutic purposes are attempted.

TL;DR: The role of mTOR inhibitors in cancer treatment continues to evolve as new compounds are continuously being disclosed, and efforts to identify markers of resistance and sensitivity to mTOR inhibition that could prove useful in the emerging field of personalized medicine are highlighted.

TL;DR: A comprehensive review on emerging targeted therapies for treating TNBCs is presented, including the promising approach of immunotherapy and the prognostic value of tumor-infiltrating lymphocytes.

TL;DR: The involvement of arginase in cardiovascular and nervous system dysfunction, and potential therapeutic interventions targeting excessArginase activity and expression are reviewed.

TL;DR: A credible transport model must account for monoaminergic neurons' distinct mode of action and link this to subtle differences in activity and undesired, potentially deleterious effects.

TL;DR: The current challenge remains in the development of potent selective inhibitors that would specifically target HDAC8 with fewer adverse effects compared with pan-HDAC inhibitors.

TL;DR: Trastuzumab (TRZ), a humanized anti-HER2 monoclonal antibody, is currently recommended as first-line treatment for patients with metastatic HER2(+) tumors, but the use of TRZ may be limited by the development of drug intolerance, such as cardiac dysfunction.

TL;DR: Two recent advances in understanding NO-mediated signaling - nitrated fatty acids (NO2-FAs) and S-guanylation - are presented and suggestions for future directions in NO-related studies on the liver are suggested.

TL;DR: The role of SIRT2 in inflammation and oxidative stress due to the possible implications for metabolic disorders is covered, and its potential as a therapeutic target for the prevention and treatment of type 2 diabetes is considered.

TL;DR: Current translational attempts to develop agonists at proresolving targets as a strategy to rectify chronic inflammatory status are discussed and it is reasoned this new approach will lead to the identification of better drugs that will establish a new branch of pharmacology, 'resolution pharmacology'.

TL;DR: In chronic viral infections, preclinical data reveal that targeting PD-1 and its ligands can improve T cell responses and virus clearance, and there is also promise in stimulating this pathway for the treatment of autoimmune and inflammatory disorders.

TL;DR: Based on findings to date, PLD1/2 inhibition may be of more utility in acute rather than chronic settings, although this generalization will depend on the specific risks and benefits in each disease setting.

TL;DR: Observations suggest that effective therapeutic approaches designed to combat neurodegenerative diseases could be aimed at enhancing the ability of the cell to maintain the homeostasis of the metastable subproteome.

TL;DR: The next generation of clinical trials and potential approaches, 'smart' and responsive encapsulation systems, sophisticated and multifunctional devices, and novel imaging tools are discussed, together with the future challenges in the field.

TL;DR: The pathophysiological role of apoC-III in TG metabolism and the evidence supporting this apolipoprotein as an emerging target for hypertriglyceridemia (HTG) and associated cardiovascular disorders are reviewed.

TL;DR: In this paper, the role of tyrosine phosphatases and TCPTP in the development of insulin resistance in hypothalamic neurons appears to have a key role in the exacerbation of diet-induced obesity.

TL;DR: Two pathways that are regarded as interesting novel therapeutic targets in the field of rheumatology: the Janus kinase (JAK) pathway and the T helper-17 (Th17) pathway are discussed.

TL;DR: The role of hydrogen sulfide (H2S) in the pathogenesis of EDF is reviewed, one of the fastest advancing research topics, and therapeutics aimed at remedying altered H2S bioavailability may benefit all.

TL;DR: Elabela/Toddler is a new apelin receptor ligand in the human cardiovascular system and Enhancing apelin signalling is beneficial in pulmonary arterial hypertension.

TL;DR: The combined effects of anticholinergic therapy on M3-mediated bronchoconstriction, mucus secretion, inflammation, and remodeling may account for the positive outcome of treatment with these drugs for patients with chronic pulmonary obstructive disease (COPD) or asthma.

TL;DR: The GPCR heterotetramer offers an optimal framework for a canonical antagonistic interaction between activated Gs and Gi proteins, which can simultaneously bind to their respective preferred receptors and to adenylyl cyclase (AC) catalytic units.

TL;DR: Recent advances in T GR5 research are summarized, focusing on the downstream effector pathways that are modulated by TGR5 activators, and on its therapeutic potential in inflammatory and metabolic diseases.

TL;DR: This work proposes menstruating tissue as the trigger for inflammatory pain in endometriosis through the activation of innate immune cells and peripheral nerve endings and speculate how innovative treatment modalities beyond hormonal treatment will improve patients' lives.