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 [...]
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 [...]
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 [...]
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 (CDs). Here, we test the assumption that toxicity is exacerbated by dosing duration by comparing the incidence and severity of target organ toxicities in these [...]
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, methodologies such as Western blotting and transient cell reporter assays have been used to identify and characterize SERD compounds, but [...]