Bernard Testa Libri

Informatics and robotics drive a technological revolution in drug research, underpinning combinatorial chemistry that produces thousands of compounds and high-throughput bioassays that screen them for activity. This results in an overwhelming number of 'hits' that populate databases. However, these compounds can be advantageous if properly evaluated for 'drugability', focusing on 'drug-like' properties such as pharmacokinetic (PK) behavior. PK profiling of bioactive compounds is essential for identifying the most promising candidates. Additionally, the less visible structure-property and structure-ADME relationships that arise from PK profiling provide valuable insights for designing new synthetic series. The book emphasizes the profiling of ADME properties (absorption, distribution, metabolism, and excretion) and highlights significant advancements in biological, physicochemical, and computational strategies in recent years. Contributions from international authorities and experts from academia and industry present cutting-edge concepts, methods, and technologies currently in use or under development in drug research. The work includes 28 chapters and a CD-ROM featuring invited lectures, oral communications, and posters from the Third LogP Symposium on 'Physicochemical and Biological Profiling in Drug Research,' held at ETH Zurich in March 2004.

Many drugs and other xenobiotics (e. g., preservatives, insecticides, and plastifiers) contain hydrolyzable moieties such as ester or amide groups. In biological media, such foreign compounds are, therefore, important substrates for hydrolytic reactions catalyzed by hydrolases or proceeding non-enzymatically. Despite their significance, until now, no book has been dedicated to hydrolysis and hydrolases in the metabolism of drugs and other xenobiotics. This work fills a gap in the literature and reviews metabolic reactions of hydrolysis and hydarion from the point of views of enzymes, substrates, and reactions.

In the current era of combinatorial chemistry and high-throughput technologies, thousands of bioactive compounds, known as hits, are identified. However, the journey from hits to lead compounds and ultimately to optimized clinical candidates is lengthy and fraught with challenges, particularly in screening, designing, and optimizing pharmacokinetic properties. This has become a significant bottleneck in drug research. To address the high attrition rates of compounds due to hidden pharmacokinetic issues, researchers are integrating structure-permeation, structure-distribution, structure-metabolism, and structure-toxicity relations into drug design. Advanced biological, physicochemical, and computational methods are being developed to enhance the clinical relevance of drug design and to swiftly eliminate compounds with poor properties. This comprehensive work features contributions from international experts, outlining modern strategies to optimize gastrointestinal absorption, protein binding, brain permeation, and metabolic profiles. Biological strategies include cell cultures and high-throughput screening, while physicochemical strategies focus on solubility, lipophilicity, and related molecular properties as predictors of pharmacokinetic behavior. The book also delves into computational strategies like virtual screening and molecular modeling. It offers insights into molecular properties from both biological and physicochemi