40 Years of Trends in Pharmacological Sciences: Blending Man and Machine
Publication date: Available online 11 July 2019Source: Trends in Pharmacological SciencesAuthor(s): Kusumika Mukherjee (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - July 13, 2019 Category: Drugs & Pharmacology Source Type: research

Deep Aging Clocks: The Emergence of AI-Based Biomarkers of Aging and Longevity
Publication date: Available online 3 July 2019Source: Trends in Pharmacological SciencesAuthor(s): Alex Zhavoronkov, Polina MamoshinaFirst published in 2016, predictors of chronological and biological age developed using deep learning (DL) are rapidly gaining popularity in the aging research community. These deep aging clocks can be used in a broad range of applications in the pharmaceutical industry, spanning target identification, drug discovery, data economics, and synthetic patient data generation. We provide here a brief overview of recent advances in this important subset, or perhaps superset, of aging clocks that ha...
Source: Trends in Pharmacological Sciences - July 5, 2019 Category: Drugs & Pharmacology Source Type: research

Artificial Intelligence: A Novel Approach for Drug Discovery
Publication date: Available online 3 July 2019Source: Trends in Pharmacological SciencesAuthor(s): Óscar Díaz, James A.R. Dalton, Jesús GiraldoMolecular dynamics (MD) simulations can mechanistically explain receptor function. However, the enormous data sets that they may imply can be a hurdle. Plante and colleagues (Molecules, 2019) recently described a machine learning approach to the analysis of MD simulations. The approach successfully classified ligands and identified functional receptor motifs and thus it seems promising for mechanism-based drug discovery. (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - July 5, 2019 Category: Drugs & Pharmacology Source Type: research

Max-imizing the Attenuation of Myc Using Small Molecules
Publication date: Available online 4 July 2019Source: Trends in Pharmacological SciencesAuthor(s): Shelton R. Boyd, Damian W. YoungIt has been a widely held notion within the biomedical research community that the reliable modulation of transcription factors with small molecules would represent a holy grail, given their role in directly potentiating oncogenic programs. Among the transcription factors that have been held in highest regard is Myc, since its dysregulation is among the most recurrent events in human cancer. Despite intense efforts, the ability to identify compounds that bind directly to Myc, resulting in its f...
Source: Trends in Pharmacological Sciences - July 5, 2019 Category: Drugs & Pharmacology Source Type: research

The Missing Pieces of Artificial Intelligence in Medicine
Publication date: Available online 2 July 2019Source: Trends in Pharmacological SciencesAuthor(s): Coryandar Gilvary, Neel Madhukar, Jamal Elkhader, Olivier ElementoStakeholders across the entire healthcare chain are looking to incorporate artificial intelligence (AI) into their decision-making process. From early-stage drug discovery to clinical decision support systems, we have seen examples of how AI can improve efficiency and decrease costs. In this Opinion, we discuss some of the key factors that should be prioritized to enable the successful integration of AI across the healthcare value chain. In particular, we belie...
Source: Trends in Pharmacological Sciences - July 4, 2019 Category: Drugs & Pharmacology Source Type: research

Editorial Board
Publication date: July 2019Source: Trends in Pharmacological Sciences, Volume 40, Issue 7Author(s): (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - June 22, 2019 Category: Drugs & Pharmacology Source Type: research

The Vast Structural Diversity of Antimicrobial Peptides
Publication date: July 2019Source: Trends in Pharmacological Sciences, Volume 40, Issue 7Author(s): Johannes Koehbach, David J. CraikAntimicrobial peptides (AMPs) occur in all kingdoms of life and are integral to host defense. They have diverse structures and target a variety of organisms, both by nonspecific membrane interactions and via specific targets. Here we discuss the structures of AMPs from the four main classes currently recognized – that is, peptides with (i) α-helical, (ii) β-sheet, (iii) αβ, or (iv) non-αβ elements – as well as the growing pool of complex topologies...
Source: Trends in Pharmacological Sciences - June 22, 2019 Category: Drugs & Pharmacology Source Type: research

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Publication date: July 2019Source: Trends in Pharmacological Sciences, Volume 40, Issue 7Author(s): (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - June 22, 2019 Category: Drugs & Pharmacology Source Type: research

Artificial Intelligence for Pharma: Time for Internal Investment
Publication date: Available online 13 June 2019Source: Trends in Pharmacological SciencesAuthor(s): Peter V. HenstockArtificial intelligence (AI) has achieved human-level capabilities and continues to rapidly improve. For the pharmaceutical industry, AI can improve decision-making and transform the quest for better medicines. The keys are investing in data management and in internal AI talent who can create value by leveraging corporate data to tackle crucial business problems. (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - June 14, 2019 Category: Drugs & Pharmacology Source Type: research

Predicting and Understanding the Human Microbiome’s Impact on Pharmacology
Publication date: Available online 3 June 2019Source: Trends in Pharmacological SciencesAuthor(s): Reese Hitchings, Libusha KellyOur bodies each possess a unique and dynamic collection of microbes and viruses, collectively the ‘microbiome’, with distinct metabolic capacities from our human cells. Unforeseen modification of drugs by the microbiome can drastically alter their clinical effectiveness, with the most dramatic cases leading to fatal drug interactions. Pharmaceuticals can be activated, deactivated, toxified, or release metabolites that alter the ‘canonical’ pharmacokinetics of the drug. Thu...
Source: Trends in Pharmacological Sciences - June 4, 2019 Category: Drugs & Pharmacology Source Type: research

Genetic Insights for Drug Development in NAFLD
Publication date: Available online 31 May 2019Source: Trends in Pharmacological SciencesAuthor(s): Mohammed Eslam, Jacob GeorgeDrug development is a costly, time-consuming, and challenging endeavour, with only a few agents reaching the threshold of approval for clinical use. Therefore, approaches to more efficiently identify targets that are likely to translate to clinical benefit are required. Interrogation of the human genome in large patient cohorts has rapidly advanced our knowledge of the genetic architecture and underlying mechanisms of many diseases, including nonalcoholic fatty liver disease (NAFLD). There are no a...
Source: Trends in Pharmacological Sciences - June 1, 2019 Category: Drugs & Pharmacology Source Type: research

Editorial Board and Contents
Publication date: June 2019Source: Trends in Pharmacological Sciences, Volume 40, Issue 6Author(s): (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - May 31, 2019 Category: Drugs & Pharmacology Source Type: research

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Publication date: June 2019Source: Trends in Pharmacological Sciences, Volume 40, Issue 6Author(s): (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - May 31, 2019 Category: Drugs & Pharmacology Source Type: research

Thiol-Based Drugs in Pulmonary Medicine: Much More than Mucolytics
Publication date: Available online 27 May 2019Source: Trends in Pharmacological SciencesAuthor(s): Mario Cazzola, Luigino Calzetta, Clive Page, Paola Rogliani, Maria Gabriella MateraThiol-based drugs are considered as mucolytics because they decrease the viscosity and mostly decrease the elasticity of bronchial secretions by reducing disulfide bonds in proteins. However, they can also act as antioxidant drugs directly through free sulfhydryl groups that serve as a source of reducing equivalents, as well as indirectly through the replenishment of intracellular glutathione (GSH) levels. Modulation of neurokinin A levels may ...
Source: Trends in Pharmacological Sciences - May 28, 2019 Category: Drugs & Pharmacology Source Type: research

Towards a Comprehensive Understanding of Anesthetic Mechanisms of Action: A Decade of Discovery
Publication date: Available online 27 May 2019Source: Trends in Pharmacological SciencesAuthor(s): Hugh C. Hemmings, Paul M. Riegelhaupt, Max B. Kelz, Ken Solt, Roderic G. Eckenhoff, Beverley A. Orser, Peter A. GoldsteinSignificant progress has been made in the 21st century towards a comprehensive understanding of the mechanisms of action of general anesthetics, coincident with progress in structural biology and molecular, cellular, and systems neuroscience. This review summarizes important new findings that include target identification through structural determination of anesthetic binding sites, details of receptors and...
Source: Trends in Pharmacological Sciences - May 27, 2019 Category: Drugs & Pharmacology Source Type: research

Updating Neuroimmune Targets in Central Nervous System Dysfunction
Publication date: Available online 23 May 2019Source: Trends in Pharmacological SciencesAuthor(s): L.A. Valente, L.R. Begg, A.J. FilianoDisorders of the central nervous system (CNS) have many etiologies compounded by limited options for treatment. The lack of successful treatments for these disorders stems from the difficulty of gaining effective access to the CNS through the blood–brain barrier, and the irreplaceable nature of neurons. Here, we review recent advances in the field of neuroimmunology and discuss novel strategies for targeting microglia, meningeal lymphatics, and the peripheral immune system that may l...
Source: Trends in Pharmacological Sciences - May 25, 2019 Category: Drugs & Pharmacology Source Type: research

Deep Learning to Therapeutically Target Unreported Complexes
Publication date: Available online 21 May 2019Source: Trends in Pharmacological SciencesAuthor(s): Ariel FernándezThe disruption of large protein–protein (PP) interfaces remains a challenge in targeted therapy. Designing drugs that compete with binding partners is daunting, especially when the structure of the protein complex is unknown. To address the problem we propose a deep protein databank (PDB) learning platform to discover targetable epitopes for complex-disruptive leads. (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - May 22, 2019 Category: Drugs & Pharmacology Source Type: research

Targeting Non-coding RNA Sensitizes Cancer Cells to Drugs
Publication date: Available online 20 May 2019Source: Trends in Pharmacological SciencesAuthor(s): Mo Yang, John S. SchneeklothRecently, Costales and colleagues (J. Am. Chem. Soc. 2019;141:2960–2974) reported a bivalent small molecule inhibitor of primary miRNA (pri-miR)-515. Perturbation of pri-miR-515 results in the upregulation of HER2 protein levels, rendering HER2– breast cancer cells more sensitive to Herceptin treatment. This strategy represents a novel pharmacological approach to selectively modulating disease-relevant proteins in tumor cells. (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - May 22, 2019 Category: Drugs & Pharmacology Source Type: research

Diet Drugs Trick Mosquitoes into Feeling Full
Publication date: Available online 20 May 2019Source: Trends in Pharmacological SciencesAuthor(s): Sarah E. Maguire, Christopher J. PotterAfter a bloodmeal, Aedes aegypti mosquitoes lose interest in bloodfeeding. Duvall et al. (Cell 2019;176:687–701) determined that the neuropeptide Y (NPY)-like receptor 7 (NPYLR7) controls mosquito satiety and also identified six NPYLR7 drug targets that suppress biting. This work highlights an innovative approach in vector control linking insect behavior to drug discovery. (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - May 22, 2019 Category: Drugs & Pharmacology Source Type: research

Prescient Indices of Activity: The Application of Functional System Sensitivity to Measurement of Drug Effect
Publication date: Available online 17 May 2019Source: Trends in Pharmacological SciencesAuthor(s): Terry KenakinThrough pharmacological procedures, indices of drug activity can be obtained that transcend the systems in which they are measured. If (i) affinity, (ii) efficacies, (iii) orthosteric versus allosteric interaction, and (iv) rate of receptor offset can be determined, activity can be predicted in all systems. This can yield more detailed profiles (fingerprints) of efficacy to better define the required activities of follow-up molecules should the original candidates fail in the clinic. The use of functional assays ...
Source: Trends in Pharmacological Sciences - May 18, 2019 Category: Drugs & Pharmacology Source Type: research

Inimitable Paul Talalay (1923–2019)
Publication date: Available online 16 May 2019Source: Trends in Pharmacological SciencesAuthor(s): Jed W. Fahey, Theresa A. ShapiroPharmacology lost a pioneer and champion with the passing of Paul Talalay. A brilliant scientist and inspiring mentor, he had been the John Jacob Abel Distinguished Service Professor of Pharmacology and Molecular Sciences at Johns Hopkins Medical School. He died at age 95, after a full life, on 10 March 2019. (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - May 17, 2019 Category: Drugs & Pharmacology Source Type: research

Deciphering the Chemical Lexicon of Host–Gut Microbiota Interactions
Publication date: Available online 9 May 2019Source: Trends in Pharmacological SciencesAuthor(s): Gael R. Nicolas, Pamela V. ChangThe human intestine harbors an immense, diverse, and critical population of bacteria that has effects on numerous aspects of host physiology, immunity, and disease. Emerging evidence suggests that many of the interactions between the host and the gut microbiota are mediated via the microbial metabolome, or the collection of small-molecule metabolites produced by intestinal bacteria. This review summarizes findings from recent work by focusing on different classes of metabolites produced by the g...
Source: Trends in Pharmacological Sciences - May 11, 2019 Category: Drugs & Pharmacology Source Type: research

Cancer and Microenvironment Plasticity: Double-Edged Swords in Metastasis
Publication date: Available online 8 May 2019Source: Trends in Pharmacological SciencesAuthor(s): Xueqian Zhuang, Hao Zhang, Guohong HuCancer initiates at one site (primary tumor) and, in most cases, spreads to other distant organs (metastasis). During the multistep process of metastasis, primary tumor cells acquire cellular and phenotypic plasticity to survive and thrive in different environments. Moreover, cancer cells also utilize and educate microenvironmental components by reshaping them into accomplices of metastasis. Recent studies have identified a plethora of new molecular and cellular modulators of metastasis tha...
Source: Trends in Pharmacological Sciences - May 9, 2019 Category: Drugs & Pharmacology Source Type: research

Pharmacological Modulation of Transcriptional Coregulators in Cancer
Publication date: Available online 8 May 2019Source: Trends in Pharmacological SciencesAuthor(s): Timothy R. Bishop, Yuxiang Zhang, Michael A. ErbUpon binding of transcription factors to cis-regulatory DNA sequences, transcriptional coregulators are required for the activation or suppression of chromatin-dependent transcriptional signaling. These coregulators are frequently implicated in oncogenesis via causal roles in dysregulated, malignant transcriptional control and represent one of the fastest-growing target classes in small-molecule drug discovery. However, challenges in targeting coregulators include identifying evi...
Source: Trends in Pharmacological Sciences - May 9, 2019 Category: Drugs & Pharmacology Source Type: research

GPCRomics: An Approach to Discover GPCR Drug Targets
Publication date: Available online 8 May 2019Source: Trends in Pharmacological SciencesAuthor(s): Paul A. Insel, Krishna Sriram, Matthew W. Gorr, Shu Z. Wiley, Alexander Michkov, Cristina Salmerón, Amy M. ChinnG protein-coupled receptors (GPCRs) are targets for ∼35% of approved drugs but only ∼15% of the ∼800 human GPCRs are currently such targets. GPCRomics, the use of unbiased, hypothesis-generating methods [e.g., RNA-sequencing (RNA-seq)], with tissues and cell types to identify and quantify GPCR expression, has led to the discovery of previously unrecognized GPCRs that contribute to functional respon...
Source: Trends in Pharmacological Sciences - May 9, 2019 Category: Drugs & Pharmacology Source Type: research

Novel Approaches to Persistent Pain Therapy
Publication date: Available online 8 May 2019Source: Trends in Pharmacological SciencesAuthor(s): Marco Sisignano, Michael J. Parnham, Gerd GeisslingerPersistent and neuropathic pain affects> 15% of the global population. Apart from being an individual burden to the patient, persistent pain causes considerable subsequent costs in global healthcare systems. Despite the efforts of pharmaceutical companies to develop novel analgesics, pharmacological options for the therapy of persistent and/or neuropathic pain are limited. We discuss here novel approaches to persistent pain therapy that are independent of classical t...
Source: Trends in Pharmacological Sciences - May 9, 2019 Category: Drugs & Pharmacology Source Type: research

Adding Nanotechnology to the Metastasis Treatment Arsenal
Publication date: Available online 7 May 2019Source: Trends in Pharmacological SciencesAuthor(s): Debarshi Banerjee, Artur Cieslar-Pobuda, Geyunjian Harry Zhu, Emilia Wiechec, Hirak K. PatraMetastasis is a major cause of cancer-related mortality, accounting for 90% of cancer deaths. The explosive growth of cancer biology research has revealed new mechanistic network information and pathways that promote metastasis. Consequently, a large number of antitumor agents have been developed and tested for their antimetastatic efficacy. Despite their exciting cytotoxic effects on tumor cells in vitro and antitumor activities in pre...
Source: Trends in Pharmacological Sciences - May 9, 2019 Category: Drugs & Pharmacology Source Type: research

Designer Drugs for Designer Receptors: Unlocking the Translational Potential of Chemogenetics
Publication date: Available online 6 May 2019Source: Trends in Pharmacological SciencesAuthor(s): Ofer Yizhar, J. Simon WiegertChemogenetic techniques allow selective manipulation of neurons by activating engineered actuator proteins with otherwise inert effector molecules. A recent study (Magnus et al. Science 2019;364:eaav5282) describes the coevolution of highly potent actuator–effector pairs based on a clinically approved antismoking drug. These tools allow selective excitation or inhibition of neurons in the living brain with high specificity and no detectable side-effects. (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - May 7, 2019 Category: Drugs & Pharmacology Source Type: research

Discovery of Allosteric Inhibition of Human ATP-Citrate Lyase
Publication date: Available online 6 May 2019Source: Trends in Pharmacological SciencesAuthor(s): Carlotta GranchiATP-citrate lyase (ACLY) is an enzyme that links glycolysis to lipid metabolism. To date only partial X-ray structures of ACLY have been solved, thus limiting the design of novel inhibitors. Wei and colleagues (published online in Nature April 3, 2019) now report the full X-ray structure of human ACLY in complex with NDI-091143, revealing an appealing allosteric inhibition mechanism for this compound. (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - May 7, 2019 Category: Drugs & Pharmacology Source Type: research

Editorial Board and Contents
Publication date: May 2019Source: Trends in Pharmacological Sciences, Volume 40, Issue 5Author(s): (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - April 20, 2019 Category: Drugs & Pharmacology Source Type: research

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Publication date: May 2019Source: Trends in Pharmacological Sciences, Volume 40, Issue 5Author(s): (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - April 20, 2019 Category: Drugs & Pharmacology Source Type: research

Rethinking Alkylating(-Like) Agents for Solid Tumor Management
Publication date: Available online 9 April 2019Source: Trends in Pharmacological SciencesAuthor(s): Hélène Lajous, Bénédicte Lelièvre, Elodie Vauléon, Philippe Lecomte, Emmanuel GarcionAlthough old molecules, alkylating agents and platinum derivatives are still widely used in the treatment of various solid tumors. However, systemic toxicity and cellular resistance mechanisms impede their efficacy. Innovative strategies, including local administration, optimization of treatment schedule/dosage, synergistic combinations, and the encapsulation of bioactive molecules in smart, multifun...
Source: Trends in Pharmacological Sciences - April 10, 2019 Category: Drugs & Pharmacology Source Type: research

Unexpected Synergy Reveals New Therapeutic Strategy in SCLC
Publication date: Available online 8 April 2019Source: Trends in Pharmacological SciencesAuthor(s): Benjamin J. Drapkin, Anna F. FaragoDNA damage repair (DDR) inhibition and immune checkpoint blockade (ICB) have each individually shown modest clinical activity in small cell lung cancer (SCLC). Recently, Sen and colleagues (Cancer Discov. 2019;https://doi.org/10.1158/2159-8290.CD-18-1020) demonstrated that DDR inhibition can activate the stimulator of interferon genes (STING) innate immune pathway, providing strong rationale for combining DDR inhibition and ICB to treat SCLC. (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - April 9, 2019 Category: Drugs & Pharmacology Source Type: research

Triptolide and Its Derivatives as Cancer Therapies
Publication date: Available online 8 April 2019Source: Trends in Pharmacological SciencesAuthor(s): Pawan Noel, Daniel D. Von Hoff, Ashok K. Saluja, Mohana Velagapudi, Erkut Borazanci, Haiyong HanTriptolide, a compound isolated from a Chinese medicinal herb, possesses potent antitumor, immunosuppressive, and anti-inflammatory properties, but is clinically limited due to its poor solubility, bioavailability, and toxicity. Recently, Minnelide, a water-soluble prodrug of triptolide, was shown to have potent antitumor activity in various preclinical cancer models. Minnelide is currently in Phase II clinical trials for treatmen...
Source: Trends in Pharmacological Sciences - April 9, 2019 Category: Drugs & Pharmacology Source Type: research

Nature-Derived Peptides: A Growing Niche for GPCR Ligand Discovery
Publication date: Available online 5 April 2019Source: Trends in Pharmacological SciencesAuthor(s): Edin Muratspahić, Michael Freissmuth, Christian W. GruberG protein-coupled receptors (GPCRs) represent important drug targets, as they regulate pivotal physiological processes and they have proved to be readily druggable. Natural products have been and continue to be amongst the most valuable sources for drug discovery and development. Here, we surveyed small molecules and (poly-)peptides derived from plants, animals, fungi, and bacteria, which modulate GPCR signaling. Among naturally occurring compounds, peptides from plan...
Source: Trends in Pharmacological Sciences - April 6, 2019 Category: Drugs & Pharmacology Source Type: research

Targeting SOCS Proteins to Control JAK-STAT Signalling in Disease
Publication date: Available online 2 April 2019Source: Trends in Pharmacological SciencesAuthor(s): Gillian A. Durham, Jamie J.L. Williams, M. Talat Nasim, Timothy M. PalmerDefective regulation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signalling pathway in cancers, haematological diseases, and chronic inflammatory conditions highlights its clinical significance. While several biologic and small molecule therapeutics targeting this pathway have been developed, these have several limitations. Therefore, there is a need to identify new targets for intervention. Suppressor of cytokine sig...
Source: Trends in Pharmacological Sciences - April 3, 2019 Category: Drugs & Pharmacology Source Type: research

Editorial Board and Contents
Publication date: April 2019Source: Trends in Pharmacological Sciences, Volume 40, Issue 4Author(s): (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - March 22, 2019 Category: Drugs & Pharmacology Source Type: research

Care for Rare: Spotlight on Rare Diseases
Publication date: April 2019Source: Trends in Pharmacological Sciences, Volume 40, Issue 4Author(s): Kusumika Mukherjee (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - March 22, 2019 Category: Drugs & Pharmacology Source Type: research

Therapeutic Prospects for Friedreich’s Ataxia
Publication date: April 2019Source: Trends in Pharmacological Sciences, Volume 40, Issue 4Author(s): Siyuan Zhang, Marek Napierala, Jill S. NapieralaFriedreich’s ataxia (FRDA) is a progressive disease affecting multiple organs that is caused by systemic insufficiency of the mitochondrial protein frataxin. Current therapeutic strategies aim to elevate frataxin levels and/or alleviate the consequences of frataxin deficiency. Recent significant advances in the FRDA therapeutic pipeline are bringing patients closer to a cure. (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - March 22, 2019 Category: Drugs & Pharmacology Source Type: research

A Coordinated Attack: Rett Syndrome Therapeutic Development
Publication date: April 2019Source: Trends in Pharmacological Sciences, Volume 40, Issue 4Author(s): Rocco G. Gogliotti, Colleen M. NiswenderRett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the Methyl CpG binding protein 2 (MeCP2) gene. This Science & Society article focuses on pharmacological strategies that attack RTT treatment from multiple angles, including drug repurposing and de novo discovery efforts, and discusses the impacts of preclinical study design and translationally relevant outcome measures. (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - March 22, 2019 Category: Drugs & Pharmacology Source Type: research

Adhesion G Protein-Coupled Receptors as Drug Targets for Neurological Diseases
Publication date: Available online 11 March 2019Source: Trends in Pharmacological SciencesAuthor(s): Christopher J. Folts, Stefanie Giera, Tao Li, Xianhua PiaoThe family of adhesion G protein-coupled receptors (aGPCRs) consists of 33 members in humans. Although the majority are orphan receptors with unknown functions, many reports have demonstrated critical functions for some members of this family in organogenesis, neurodevelopment, myelination, angiogenesis, and cancer progression. Importantly, mutations in several aGPCRs have been linked to human diseases. The crystal structure of a shared protein domain, the GPCR Autop...
Source: Trends in Pharmacological Sciences - March 12, 2019 Category: Drugs & Pharmacology Source Type: research

ABHD6: Its Place in Endocannabinoid Signaling and Beyond
Publication date: Available online 7 March 2019Source: Trends in Pharmacological SciencesAuthor(s): Jessica K. Cao, Joshua Kaplan, Nephi StellaThe endocannabinoid (eCB) signaling system modulates neurotransmission and inflammation, among other physiological functions. Its newest member, α/β-hydrolase domain-containing 6 (ABHD6), has emerged as a promising therapeutic target to treat several devastating diseases, including epilepsy. Here, we review the molecular mechanisms that mediate and control eCB signaling and, within it, the specific role of ABHD6. We also discuss how ABHD6 controls the abundance of additio...
Source: Trends in Pharmacological Sciences - March 9, 2019 Category: Drugs & Pharmacology Source Type: research

Does Divergent Binding Pocket Closure Drive Ligand Bias for Class A GPCRs?
Publication date: Available online 6 March 2019Source: Trends in Pharmacological SciencesAuthor(s): Marcel Bermudez, Andreas BockGPCRs couple to intracellular transducer proteins, which reciprocally closes the extracellular ligand binding pocket, a process called allosteric coupling. Biased agonists preferentially stimulate receptor coupling to specific signaling pathways. Here, we postulate that agonists with extended binding modes selectively interfere with binding pocket closure, which results in divergent allosteric coupling, eventually leading to ligand bias. (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - March 7, 2019 Category: Drugs & Pharmacology Source Type: research

Targeting Mechanosensitive Transcription Factors in Atherosclerosis
We present here a comprehensive overview of the role of MSTFs in atherosclerosis, and highlight future directions for developing novel therapeutic agents by targeting MSTFs. (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - February 28, 2019 Category: Drugs & Pharmacology Source Type: research

Neuropharmacological Insight from Allosteric Modulation of mGlu Receptors
Publication date: Available online 26 February 2019Source: Trends in Pharmacological SciencesAuthor(s): Branden J. Stansley, P. Jeffrey ConnThe metabotropic glutamate (mGlu) receptors are a family of G-protein-coupled receptors (GPCRs) that regulate cell physiology throughout the nervous system. The potential of mGlu receptors as therapeutic targets has been bolstered by current research that has provided insight into the diverse modes of mGlu activation and signaling. In particular, the allosteric modulation of mGlu receptors represents a major area of focus in studies of basic pharmacology as well as drug development, la...
Source: Trends in Pharmacological Sciences - February 27, 2019 Category: Drugs & Pharmacology Source Type: research

Editorial Board and Contents
Publication date: March 2019Source: Trends in Pharmacological Sciences, Volume 40, Issue 3Author(s): (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - February 22, 2019 Category: Drugs & Pharmacology Source Type: research

Patterns of Genomic Instability in Breast Cancer
Publication date: Available online 6 February 2019Source: Trends in Pharmacological SciencesAuthor(s): Murugan Kalimutho, Katia Nones, Sriganesh Srihari, Pascal H.G. Duijf, Nicola Waddell, Kum Kum KhannaBreast cancer is one of the most common cancers affecting women. Despite significant improvements in overall survival, it remains a significant cause of death worldwide. Genomic instability (GI) is a hallmark of cancer and plays a pivotal role in breast cancer development and progression. In the past decade, high-throughput technologies have provided a wealth of information that has facilitated the identification of a diver...
Source: Trends in Pharmacological Sciences - February 6, 2019 Category: Drugs & Pharmacology Source Type: research

New Frontiers in Lp(a)-Targeted Therapies
Publication date: Available online 4 February 2019Source: Trends in Pharmacological SciencesAuthor(s): Matthew J. Borrelli, Amer Youssef, Michael B. Boffa, Marlys L. KoschinskyInterest in lipoprotein (a) [Lp(a)] has exploded over the past decade with the emergence of genetic and epidemiological studies pinpointing elevated levels of this unique lipoprotein as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve disease (CAVD). This review summarizes the most recent discoveries regarding therapeutic approaches to lower Lp(a) and presents these findings in the context of an emergi...
Source: Trends in Pharmacological Sciences - February 5, 2019 Category: Drugs & Pharmacology Source Type: research

Liquid Biopsies in Cancer Diagnosis, Monitoring, and Prognosis
Publication date: Available online 5 February 2019Source: Trends in Pharmacological SciencesAuthor(s): Gabriele De Rubis, Sabna Rajeev Krishnan, Mary BebawyLiquid biopsies, comprising the noninvasive analysis of circulating tumor-derived material (the ‘tumor circulome’), represent an innovative tool in precision oncology to overcome current limitations associated with tissue biopsies. Within the tumor circulome, circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) are the only components the clinical application of which is approved by the US Food and Drug Administration (FDA). Extracellular vesicle...
Source: Trends in Pharmacological Sciences - February 5, 2019 Category: Drugs & Pharmacology Source Type: research

Can Adding Constitutive Receptor Activity Redefine Biased Signaling Quantification?
Publication date: Available online 1 February 2019Source: Trends in Pharmacological SciencesAuthor(s): Bin Zhou, David A. Hall, Jesús GiraldoBiased signaling, the differential activation of distinct signaling pathways, is currently at the center of pharmacology. Reliable characterization of biased ligands requires robust scales applicable to all ligand classes: agonists, neutral antagonists, and inverse agonists. To this end, constitutive receptor activity should be included in the models. (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - February 2, 2019 Category: Drugs & Pharmacology Source Type: research