Fenspiride Hydrochloride

The design of novel, safe, and effective drugs to treat human diseases is a challenging venture, with toxicity being one of the main sources of attrition at later stages of development. Failure due to toxicity incurs a significant increase in costs and time to market, with multiple drugs being withdrawn from the market due to their adverse effects. Cardiotoxicity, for instance, was responsible for the failure of drugs such as fenspiride, propoxyphene, and valdecoxib. While significant effort has been dedicated to mitigate this issue by developing computational approaches that aim to identify molecules likely to be toxic, including quantitative structure-activity relationship models and machine learning methods, current approaches present limited performance and interpretability. To overcome these, we propose a new web-based computational method, cardioToxCSM, which can predict six types of cardiac toxicity outcomes, including arrhythmia, cardiac failure, heart block, hERG toxicity, hypertension, and myocardial infarction, efficiently and accurately. cardioToxCSM was developed using the concept of graph-based signatures, molecular descriptors, toxicophore matchings, and molecular fingerprints, leveraging explainable machine learning, and was validated internally via different cross validation schemes and externally via low-redundancy blind sets. The models presented robust performances with areas under ROC curves of up to 0.898 on 5-fold cross-validation, consistent with metrics on blind tests. Additionally, our models provide interpretation of the predictions by identifying whether substructures that are commonly enriched in toxic compounds were present. We believe cardioToxCSM will provide valuable insight into the potential cardiotoxicity of small molecules early on drug screening efforts. The method is made freely available as a web server at https://biosig.lab.uq.edu.au/cardiotoxcsm.

The purpose of this work is to study fenspiride for the purposes and tasks of chemical and toxicological research. The technique of chemical-toxicological study of fenspiride in urine by preliminary and confirming methods is proposed. The authors proposed a method of thin - layer chromatography in the solvent system of acetone - 25% ammonia solution (9:1) in a preliminary study of fenspiride. The Rf value of fenspiride is 0.80±0.02. The degree of extraction when used as an extractant mixture of chloroform-propanol (9:1) is 28.1±1.4% The conditions for identification of fenspiride by gas chromatography-mass spectrometry (fenspiride retention time 11.1±0.1 minutes), followed by quantitative determination of the analyte, are proposed as a confirming method. The conditions for qualitative (retention time of fenspiride 8.1±0.1 minutes) and quantitative determination of fenspiride by high-performance liquid chromatography are proposed.