Ruth Roberts and Emma Walker were featured on the front cover of Toxicology Research this month. The mother and daughter’s review article, Collaboration and competition: ethics in toxicology hit the headlines in Volume 7. The front cover was painted by Emma, an accomplished artist as well as scientist. Emma is currently studying for her Master’s [...]
Abstract: How can small-to-medium pharma and biotech companies enhance the chances of running a successful drug project and maximise the return on a limited number of assets? Having a full appreciation of the safety risks associated with proposed drug targets is a crucial element in understanding the unwanted side-effects that might stop a project in [...]
Abstract Introduction The Safety Pharmacology Society (SPS) has conducted a survey of its membership to identify industry practices related to testing considered in the Comprehensive In vitroProarrhythmia Assay (CiPA). Methods Survey topics included nonclinical approaches to address proarrhythmia issues, conduct of in silico studies, in vitro ion channel testing methods used, drugs used as positive controls during the conduct of cardiac ion [...]
Changes in the metabolome and microRNA levels in biological fluids might represent biomarkers of neurotoxicity: A trimethyltin study.
Abstract: Neurotoxicity has been linked with exposure to a number of common drugs and chemicals, yet efficient, accurate, and minimally invasive methods to detect it are lacking. Fluid-based biomarkers such as those found in serum, plasma, urine, and cerebrospinal fluid have great potential due to the relative ease of sampling but at present, data on [...]
Two of the biggest ethical challenges in pharmaceutical toxicology are the use of animals in testing and the high safety-related attrition rates in new drug development. Yet very little is invested in these two fields compared with investment in new efficacy models, new disease targets and new technologies. How can this be addressed? In this [...]
Abstract K+/Cl- cotransporter 2 (KCC2) is selectively expressed in the adult nervous system and allows neurons to maintain low intracellular Cl- levels. Thus, KCC2 activity is an essential prerequisite for fast hyperpolarizing synaptic inhibition mediated by type A γ-aminobutyric acid (GABAA) receptors, which are Cl--permeable, ligand-gated ion channels. Consistent with this, deficits in the activity of KCC2 [...]
The small molecule CLP257 does not modify activity of the K+/Cl- co-transporter KCC2 but does potentiate GABA A receptor activity.
Read more here: RA Cardarelli, K Jones, LI Pisella, HJ Wobst, LJ McWilliams, PM Sharpe, MP Burnham, DJ Baker, I Chudotvorova, J Guyot, L Silayeva, DH Morrow, N Dekker, S Zicha, PA Davies, J Holenz, ME Duggan, J Dunlop, RJ Mather, Q Wang, I Medina, NJ Brandon, TZ Deeb and SJ Moss. The small molecule CLP257 [...]
This poster, presented at the Gordon Research Conference in August 2017, concluded that: Target safety assessments: Provide expert assessment and interpretation of literature and available databases and are invaluable in identifying and avoiding target-related risks Inform target selection and/or prioritisation early in discovery Should contain the level of detail appropriate to the project stage Should [...]
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 taken [...]
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 [...]