An In Silico Test Battery for Rapid Evaluation of Genotoxic and Carcinogenic Potential of Chemicals
Poster Apr 04, 2012
Kiril Lanevskij, Liutauras Juska, Justas Dapkunas, Andrius Sazonovas, Pranas Japertas and Remigijus Didziapetris, of ACD/Labs and Vilnius University
According to the FDA Guidance for Industry, impurities identified below the ICH qualification thresholds may be evaluated for genotoxicity and carcinogenicity based on structural activity relationship (SAR) assessments using computational software. This work is an extension of our previous study focusing on computational assessment of genotoxic impurities in drug products. Our new approach relies on a battery of probabilistic QSAR models supplemented by a knowledge-based expert system that identifies structural fragments, potentially responsible for hazardous activity. The analysis was based on experimental data obtained from FDA, and involved 21 endpoints corresponding to different mechanisms of toxic action: mutagenicity, clastogenicity, carcinogenicity, etc. Probabilistic models for most endpoints were derived using GALAS (Global, Adjusted Locally According to Similarity) modeling methodology developed in our group. The updated list of alerting groups contained 70 distinct substructures. The expert system was highly sensitive, recognizing >90% of potent carcinogens, as classified by the FDA. Sensitivity of probabilistic models ranged from about 60% to more than 90%, while maintaining high (>80%) specificity of predictions for the majority of considered assays. These results show that the described computational platform ensures sufficient prediction accuracy for rapid genotoxicity/ carcinogenicity profiling of various chemicals.
A New Tool for the Automated Sample Preparation of Whole Blood Samples by LC-MS using a Commercial AutosamplerPoster
Automated sample preparation reduces the costs per sample and minimizes sample handling errors. Usually expensive and highly specialized pipetting robots are used. However, most of these systems are not designed with a direct interface for LC-MS applications. In addition common pipetting systems are not optimized for smaller scale sample series. Here we present a new tool for liquid handling of whole blood samples and direct sample injection.
Assessment of Oral LISPRO Treatment in Ameliorating Amyloid and Tau Pathology in Transgenic Alzheimer’s Mice ModelPoster
Ionic co-crystals of lithium salicylate with organic proline (LISPRO) showed better safety and pharmacokinetic profile of lithium in plasma and brain of wild-type and transgenic Alzheimer mice model compared to lithium salts.READ MORE
Analysis of Urine SRMs Using Solid-Phase Micro Extraction, Dynamic Headspace, and Liquid Injection with Comprehensive GCxGC High Res TOFMSPoster
We used modern-day, high-resolution time-of-flight mass spectrometry (HRT) and powerful processing software to quickly and confidently identify compounds in urine.READ MORE
Comments | 0 ADD COMMENT
EMBL Conference: European Conference of Life Science Funders and Foundations
Apr 19 - Apr 20, 2018
EMBL Course: Target Engagement in Biology and Drug Discovery
Feb 19 - Feb 23, 2018