Target Safety Assessment: Strategies and Resources, Chapter 12 of Drug Safety Evaluation Methods in Molecular Biology (vol 1641), was written by Dr Richard J Brennan, a Scientific Advisor at Sanofi in the United States. The chapter presents a summary of the information types and sources that should be investigated and approaches that can be [...]
Abstract Adverse drug reactions affecting the gastrointestinal (GI) tract are a serious burden on patients, healthcare providers and the pharmaceutical industry. GI toxicity encompasses a range of pathologies in different parts of the GI tract. However, to date no specific mechanistic diagnostic/prognostic biomarkers or translatable pre-clinical models of GI toxicity exist. This review will cover [...]
Ruth Roberts is first author on one of Toxicological Sciences’ top 10% downloaded articles during the last 2 years. The paper, ‘Translational Biomarkers of Neurotoxicity: A Health and Environmental Sciences Institute Perspective on the Way Forward’ describes the challenges and opportunities in the development of biomarkers of neurotoxicity, a goal shared by scientists across academia, [...]
ApconiX Associate Jane Stewart is first author on a manuscript in the DIA peer-reviewed journal “Therapeutic Innovation and Regulatory Science” (TIRS) that has received the DIA’s 2017 Author of the Year Award. This annual award honours the author of the most accessed and downloaded article in TIRS. The article ‘Birth Control in Clinical Trials: Industry [...]
Discovery of benzothiazoles as antimycobacterial agents: Synthesis, structure–activity relationships and binding studies with Mycobacterium tuberculosis decaprenylphosphoryl-β-d-ribose 2′-oxidase Abstract We report the discovery of benzothiazoles, a novel anti-mycobacterial series, identified from a whole cell based screening campaign. Benzothiazoles exert their bactericidal activity against Mycobacterium tuberculosis (Mtb) through potent inhibition of decaprenylphosphoryl-β-d-ribose 2′-oxidase [...]
Target organ profiles in toxicity studies supporting human dosing: Does severity progress with longer duration of exposure? Abstract: We have previously reported the profile of target organs (defined as organs showing histopathological changes) in rodent and non-rodent toxicity studies conducted prior to first-time-in-man (FTiM) for 77 AstraZeneca candidate drugs [...]
A Screening Assay Cascade to Identify and Characterize Novel Selective Estrogen Receptor Downregulators (SERD’s). Abstract Here, we describe an approach to identify novel selective estrogen receptor downregulator (SERD) compounds with improved properties such as oral bioavailability and the potential of increased efficacy compared to currently marketed drug treatments. Previously, [...]
Quantification of Drug-Induced Inhibition of Canalicular Cholyl-l-Lysyl-Fluorescein Excretion From Hepatocytes by High Content Cell Imaging. Abstract We describe the use of a commercially available high content cell imaging algorithm (Cellomics Arrayscan Spot Detector) to quantify biliary excretion of the fluorescent probe substrate cholyl-l-lysyl-fluorescein (CLF) from rat hepatocytes cultured in [...]
Publishing is the lifeblood of science I love writing papers. I really enjoy the combination of creativity and logic required plus the sense of drawing a line under a piece of work. It’s also great (usually!) to get feedback from the scientific community both during and after the peer [...]
Pharmacological and electrophysiological characterization of AZSMO-23, an activator of the hERG K(+) channel Abstract: Background and Purpose: We aimed to characterize the pharmacology and electrophysiology of N-[3-(1H-benzimidazol-2-yl)-4-chloro-phenyl]pyridine-3-carboxamide (AZSMO-23), an activator of the human ether-a-go-go-related gene (hERG)-encoded K+ channel (Kv11.1). Experimental Approach: Automated electrophysiology was used to study the pharmacology of [...]
