SOT 58th Annual Meeting & ToxExpo - 1663: Talk by Dr Jane Barber of ApconiX At the Society of Toxicology 58th Annual Meeting and ToxExpo from March 10th to 14th at the Baltimore Convention Center, Dr Jane Barber of ApconiX will be giving a talk as part of the Safety Assessment: [...]
Study monitoring – What is it and why is it important to drug discovery projects? Guy Healing, Senior Toxicologist at ApconiX is interviewed by Jon Clements of Metamorphic PR Pharma companies need to ensure their drugs are safe but also that they work. In drug development, this requires numerous studies to [...]
Differential expression of cyclin-dependent kinases in the adult human retina in relation to CDK inhibitor retinotoxicity Abstract Cyclin-dependent kinases (CDKs) are a family of kinases associated predominantly with cell cycle control, making CDK inhibitors interesting candidates for anti-cancer therapeutics. However, retinal toxicity (loss of photoreceptors) has been associated with [...]
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 [...]
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 [...]
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 [...]
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 [...]
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 [...]
In vitro inhibition of the bile salt export pump correlates with risk of cholestatic drug-induced liver injury in humans. Abstract Inhibition of the activity of the human bile salt export pump (BSEP: ABCB11) has been proposed to play a role in drug-induced liver injury (DILI). To enhance understanding of [...]
