Targeting GPCR Signaling for Idiopathic Pulmonary Fibrosis Therapies
Publication date: Available online 30 January 2020Source: Trends in Pharmacological SciencesAuthor(s): Andrew J. Haak, Merrick T. Ducharme, Ana M. Diaz Espinosa, Daniel J. TschumperlinA variety of G protein-coupled receptors (GPCRs) have been implicated in the pathogenesis of pulmonary fibrosis, largely through their promotion of profibrotic fibroblast activation. By contrast, recent work has highlighted the beneficial effects of Gαs-coupled GPCRs on reducing fibroblast activation and fibrosis. This review highlights how fibrosis-promoting and -inhibiting GPCR signaling converges on downstream signaling and transcriptiona...
Source: Trends in Pharmacological Sciences - February 1, 2020 Category: Drugs & Pharmacology Source Type: research
The Interplay of the Extracellular Matrix and Stromal Cells as a Drug Target in Stroma-Rich Cancers
Publication date: Available online 31 January 2020Source: Trends in Pharmacological SciencesAuthor(s): Nina Kozlova, Joseph E. Grossman, Marcin P. Iwanicki, Taru MuranenThe tumor microenvironment (TME) is a complex neighborhood that consists of immune cells, fibroblasts, pericytes, adipocytes, endothelial and neuronal cells, and the extracellular matrix proteins. TME also consists of physical factors, such as oxygen availability, changing pH, interstitial fluid pressure, and tissue stiffness. As cancer progresses, the physical properties and the cells in the TME change significantly, impacting the efficacy of the therapies...
Source: Trends in Pharmacological Sciences - February 1, 2020 Category: Drugs & Pharmacology Source Type: research
Tetrahydroprotoberberines: A Novel Source of Pharmacotherapies for Substance Use Disorders?
Publication date: Available online 24 January 2020Source: Trends in Pharmacological SciencesAuthor(s): Maya O. Nesbit, Anthony G. PhillipsTetrahydroprotoberberines (THPBs) are a class of compounds that target both dopamine D1 and D2 families of receptors, making them attractive candidates for treating substance use disorder (SUD). The binding of some THPBs to serotonin and adrenergic receptors, in addition to dopamine receptors, gives rise to complex pharmacological profiles. Significant progress has been made over the last decade in examining these compounds for their therapeutic potential. Here, we evaluate recent discov...
Source: Trends in Pharmacological Sciences - January 25, 2020 Category: Drugs & Pharmacology Source Type: research
Identifying Missing Biosynthesis Enzymes of Plant Natural Products
Publication date: Available online 21 January 2020Source: Trends in Pharmacological SciencesAuthor(s): Thomas Dugé de Bernonville, Nicolas Papon, Marc Clastre, Sarah E. O’Connor, Vincent CourdavaultElucidating plant-specialized biosynthetic pathways has always constituted a laborious task, notably for natural products with high pharmaceutical values. Here, we discuss emerging omics-based strategies that facilitate the identification of genes from these complex metabolic pathways, paving the way to engineered supplies of these compounds through synthetic biology approaches. (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - January 22, 2020 Category: Drugs & Pharmacology Source Type: research
Targeting FGF21 for the Treatment of Nonalcoholic Steatohepatitis
Publication date: Available online 21 January 2020Source: Trends in Pharmacological SciencesAuthor(s): Mohammad Zarei, Javier Pizarro-Delgado, Emma Barroso, Xavier Palomer, Manuel Vázquez-CarreraNonalcoholic steatohepatitis (NASH), the severe stage of nonalcoholic fatty liver disease (NAFLD), is defined as the presence of hepatic steatosis with inflammation, hepatocyte injury, and different degrees of fibrosis. Although NASH affects 2–5% of the global population, no drug has been specifically approved to treat the disease. Fibroblast growth factor 21 (FGF21) and its analogs have emerged as a potential new therapeutic st...
Source: Trends in Pharmacological Sciences - January 22, 2020 Category: Drugs & Pharmacology Source Type: research
Immunotherapy for Malignant Glioma: Current Status and Future Directions
Publication date: Available online 21 January 2020Source: Trends in Pharmacological SciencesAuthor(s): Hongxiang Wang, Tao Xu, Qilin Huang, Weilin Jin, Juxiang ChenGlioma is the most common intracranial primary malignancy, with limited treatment options and a poor overall survival (OS). Immunotherapy has been used successfully in various cancers, leading to the development of similar therapies that activate the patient’s immune system to eliminate glioma. In this review, we introduce the diverse immunotherapeutic approaches available for treating glioma, highlighting the successes and challenges resulting from current cl...
Source: Trends in Pharmacological Sciences - January 22, 2020 Category: Drugs & Pharmacology Source Type: research
Opioid-Induced Adaptations of cAMP Dynamics in the Nucleus Accumbens
Publication date: Available online 18 January 2020Source: Trends in Pharmacological SciencesAuthor(s): Sarah Zych, Christopher P. FordTo investigate how opioid exposure alters dopamine (DA) responses in medium spiny neurons (MSNs), Muntean et al. used a novel cAMP sensor to track cAMP dynamics and report a coordinated effort of adaptations in D1- and D2-MSNs to integrate DA inputs and shift signaling strengths in various states of opioid dependence. (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - January 19, 2020 Category: Drugs & Pharmacology Source Type: research
Proteomics and Imaging in Crohn’s Disease: TAILS of Unlikely Allies
Publication date: Available online 14 January 2020Source: Trends in Pharmacological SciencesAuthor(s): Barbara Mainoli, Simon Hirota, Laura E. Edgington-Mitchell, Cathy Lu, Antoine DufourCrohn’s disease (CD) is a chronic relapsing inflammatory bowel disease (IBD) that may be marked by debilitating symptoms of abdominal pain and obstruction. The etiology and pathogenesis of the disease are not fully understood, and treatment with corticosteroids, biologics, and surgical intervention are the usual therapeutic options. Diagnosis, disease activity, and therapeutic response are currently assessed by endoscopy, cross-sectional...
Source: Trends in Pharmacological Sciences - January 16, 2020 Category: Drugs & Pharmacology Source Type: research
Development and Regulation of Gene and Cell-Based Therapies in Europe: A Quantification and Reflection
Publication date: Available online 13 January 2020Source: Trends in Pharmacological SciencesAuthor(s): Renske M.T. ten Ham, Anke M. Hövels, Olaf H. Klungel, Hubert G.M. Leufkens, Andre W. Broekmans, Jarno HoekmanGene and cell-based therapies (GCTs) are said to hold great promise as treatments for previously untreatable and high-burden diseases. Here, we provide insight into GCT development and regulation activities in Europe, quantify clinical and regulatory success, and compare these with other medicinal products in order to reflect on regulatory changes and challenges. (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - January 15, 2020 Category: Drugs & Pharmacology Source Type: research
Enhancing Choice and Outcomes for Therapeutic Trials in Chronic Pain: N-of-1 + Imaging (+ i)
Publication date: Available online 9 January 2020Source: Trends in Pharmacological SciencesAuthor(s): David Borsook, Jaymin Upadhyay, Richard Hargreaves, Tor WagerThe attrition of novel analgesic drugs in the clinic can be attributed in the main to two factors: failure of preclinical research findings translating into human pain conditions, and a drop-off of efficacy between proof-of-concept (i.e., Phase II trials) and pivotal, confirmatory (Phase III trials) testing. In order to enhance the efficiency of the clinical drug evaluation process and determine rapidly whether a potential therapeutic candidate gives pain relief,...
Source: Trends in Pharmacological Sciences - January 10, 2020 Category: Drugs & Pharmacology Source Type: research
Drug Screen Tugs at Common Thread for Repeat Disorders
Publication date: Available online 8 January 2020Source: Trends in Pharmacological SciencesAuthor(s): Kaalak Reddy, John Douglas Cleary, J. Andrew BerglundRepeat-associated non-ATG (RAN) translation is emerging as a driver of pathogenesis in microsatellite expansion disorders. Green and colleagues recently identified several candidate RAN translation inhibitors from a high-throughput small-molecule screen for fragile X tremor ataxia syndrome. Their study establishes a path forward for identifying inhibitors of RAN translation for multiple disorders. (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - January 9, 2020 Category: Drugs & Pharmacology Source Type: research
Ropinirole, a New ALS Drug Candidate Developed Using iPSCs
Publication date: Available online 8 January 2020Source: Trends in Pharmacological SciencesAuthor(s): Hideyuki Okano, Daisuke Yasuda, Koki Fujimori, Satoru Morimoto, Shinichi TakahashiInduced pluripotent stem cells (iPSCs) are increasingly used in the study of disease mechanisms and the development of effective disease-modifying therapies for neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Recently, three candidate anti-ALS drugs – ropinirole (ROPI), retigabine, and bosutinib – have been identified in iPSC-based drug screens and are now being evaluated in clinical trials for safety and effect...
Source: Trends in Pharmacological Sciences - January 9, 2020 Category: Drugs & Pharmacology Source Type: research
Editorial Board and Contents
Publication date: January 2020Source: Trends in Pharmacological Sciences, Volume 41, Issue 1Author(s): (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - December 28, 2019 Category: Drugs & Pharmacology Source Type: research
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Publication date: January 2020Source: Trends in Pharmacological Sciences, Volume 41, Issue 1Author(s): (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - December 28, 2019 Category: Drugs & Pharmacology Source Type: research
Insight into the Structural Features of TSPO: Implications for Drug Development
Publication date: Available online 18 December 2019Source: Trends in Pharmacological SciencesAuthor(s): Jean-Jacques Lacapere, Luminita Duma, Stephanie Finet, Michael Kassiou, Vassilios PapadopoulosThe translocator protein (TSPO), an 18-kDa transmembrane protein primarily found in the outer mitochondrial membrane, is evolutionarily conserved and widely distributed across species. In mammals, TSPO has been described as a key member of a multiprotein complex involved in many putative functions and, over the years, several classes of ligand have been developed to modulate these functions. In this review, we consider the curre...
Source: Trends in Pharmacological Sciences - December 19, 2019 Category: Drugs & Pharmacology Source Type: research
