Showing papers in "Trends in Pharmacological Sciences in 2016"

TL;DR: Targeting TDE dysregulation pathways, such as the heparanase/syndecan-1 axis, could represent novel therapeutic strategies in the quest to conquer cancer.

TL;DR: The current WEE1 inhibitors, the potential for further inhibitor development, and the challenges in the clinic for the Wee1 inhibitor strategy are summarized.

TL;DR: This work proposes that Sig-1R is a pluripotent modulator with resultant multiple functional manifestations in living systems and investigates its role in central nervous system diseases.

TL;DR: This review condense the current body of knowledge on the issue, highlighting when, where, and how adenosine exerts its protective effects in both the brain and the periphery.

TL;DR: This work reviews recent activity inStructural work with microbial P450s includes studies related to the biosynthesis of natural products and the use of parasitic and fungal P450 structures as targets for drug discovery and the utilization of information about 'drug-metabolizing' P 450s to improve drug development.

TL;DR: An overview of processes that can guide the development of antioxidant therapies in neurological diseases are provided, such as knowledge of basic redox mechanisms, unique features of brain pathophysiology, mechanisms and classes of antioxidants, and desirable properties of drug candidates.

TL;DR: The discovery of its role in selective autophagy and the description of B AG3-mediated selective macroautophagy as an adaptive mechanism to maintain cellular homeostasis, under stress as well as during aging, make BAG3 a highly interesting target for future pharmacological interventions.

TL;DR: This overview examines the current situation, highlights new natural product systems which have been found, together with re-examination of some old ones, and new technologies for their identification.

TL;DR: This review compares and contrast various features of TCRs versus CARs, with a goal of highlighting issues that need to be addressed to fully exploit the therapeutic potential of both.

TL;DR: Evidence suggesting that feedback activation of STAT3 plays a prominent role in mediating drug resistance to a broad spectrum of targeted cancer therapies and chemotherapies is focused on.

TL;DR: The cerebro- and cardiovascular risks that might be associated with CGRP blockade are reviewed and which clinical and preclinical studies should be conducted to better assess the potential safety issues of this new promising class of drug.

TL;DR: Preclinical studies provide new insights into the regulation of inflammation in epileptic brains and guide drug discovery efforts aimed at developing novel anti-inflammatory therapies for seizures and epilepsy.

TL;DR: The benefit-risk and cost-effectiveness issues of precision medicine targeting FGFRs, ALK, EGFR, and FLT3 are discussed.

TL;DR: Recent advances in US National Institutes of Health-sponsored and other clinical studies of neurosteroids for CNS disorders are described and synthetic analogs have several advantages over natural neurosteroid for clinical use because of their superior bioavailability and safety trends.

TL;DR: This review highlights some of modified and engineered proteins under development as preclinical and clinical-stage drug candidates for the treatment of cancer and provides examples of modified protein formats and modifications allowing tuning of properties such as target-binding affinity, serum half-life, stability, and immunogenicity.

TL;DR: Protein S-nitrosylation, resulting from covalent attachment of an NO group to a cysteine thiol of the target protein, is highlighted as a ubiquitous effector of NO signaling in both health and disease.

TL;DR: The major contemporary approaches utilized for the discovery of inhibitors are reviewed and a structure-based workflow is focused on, from the selection of a biological target to design.

TL;DR: This review reflects the dramatic increase in research on the role of increased expression of heme oxygenase (HO)-1/HO-2, biliverdin reductase, and HO activity on vascular disease.

TL;DR: Printing technologies are developing fast and have the potential to allow the use of versatile materials to manufacture sophisticated drug-delivery systems and biofunctional constructs for personalized treatments.

TL;DR: It is clear that non-neuronal NMDARs may participate in an array of physiological and pathophysiological processes, including but not limited to bone deposition, wound healing, insulin secretion, blood-brain barrier integrity, and myelination.

TL;DR: A more nuanced view of how the mTOR signaling pathway regulates adipose tissue biology and function is provided and approaches to modulate the activity and tissue-specific function of mTOR are described that may pave the way towards counteracting obesity and related metabolic diseases.

TL;DR: Concerns regarding the reliability of biomedical research outcomes were precipitated by two independent reports from the pharmaceutical industry that documented a lack of reproducibility in preclinical research in the areas of oncology, endocrinology, and hematology.

TL;DR: The currently available data from experiments on knockout animals suggest that the lack of non-phagocytic Nox/Duox enzymes often modifies the course and phenotype in many disease models, reinforcing the need for a more balanced view on the role of ROS in health and disease.

TL;DR: The current state of AMPK research with an emphasis on cancer is reviewed and the yet unresolved context-dependent functions of AM PK in human cancer are discussed.

TL;DR: Three voltage-gated ion channel families, CaV, HCN, and NaV, are focused on, first reviewing the preclinical data and then the human data where it exists, and altered expression, trafficking, and functioning of ion channels expressed by primary sensory neurons are proposed.

TL;DR: This review examines common foodstuffs, herbs, spices, and more exotic ingredients: kava, chocolate, black pepper, and many others that are examined in this review.

TL;DR: This work focuses on the structural and functional characteristics of APP as a cell surface receptor, and on its interaction with adaptors and signaling proteins.

TL;DR: The implicate neurons and microglia as interactive contributors to the cumulative allostatic processes creating analgesic and hedonic tolerance to opioid drugs, and include mechanistic differences both between agonists (agonist bias), and between μ- and δ-opioid receptors.

TL;DR: Adjunctive administration of 5-hydroxytryptophan SR safely elevates 5-HTExt beyond the SERT inhibitor effect in humans; however,5-HTP cannot be a clinically viable drug because of its poor pharmacokinetics.

TL;DR: This review critically assess recent trends in the development and applications of bispecific antibodies, antibody-drug conjugates, and immune checkpoint inhibitors as cancer therapeutics and highlights recent US FDA approvals and clinical trials of antibody-based cancer therapies.