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 lead ...
Source: Trends in Pharmacological Sciences - May 24, 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 21, 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 21, 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 responses and path...
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 targ...
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 19, 2019 Category: Drugs & Pharmacology Source Type: research
