Foreword

Aiming to accelerate the therapeutic interaction of the expanding chemical space and biological target space to advance drug discovery, this inaugural eBook, Advances in Combinatorial Chemistry & High Throughput Screening (ACCHTS), opens up a new avenue for rapid access to a focused collection of highly regarded contributions in the field. Importantly, ACCHTS not only highlights major conceptual advances and cutting edge technologies, but also serves as a muchneeded window to the timely, informative, and enabling resources in its parent journal CCHTS.

Although biological and biomedical advances coupled with genomics studies have uncovered a large number of potential drug targets, the number of novel target drugs that enter clinics remains dismally low at about four per year during the past thirty years. In order to rapidly translate such impressive gains in biomedical research into much-needed therapeutic agents, we must improve each step in the drug discovery process. For example, developing bioassays that faithfully reflect in vivo biological processes is essential. Expanding chemical space through innovative combinatorial chemistry and natural products-inspired approaches allows for effective interrogation of high-value targets, such as GPCRs and kinases, as well as traditionally un-druggable targets, such as protein-protein interaction interfaces. Progress in laboratory automation and highly sensitive and versatile detection technologies enables unprecedented high throughput screening operations in both industry and academia to accelerate the process of drug lead discovery and characterization. Chapters selected for this inaugural volume reflect promising developments in these critical areas. These contributions describe innovative assay platforms that include both cell-based phenotypic assays and biochemical assays for efficient HTS, and chemical methodologies for building and assessing chemicals. I hope that these chapters will set the standard for future publications to come.

While technology development is important for accelerating the process of drug discovery, rapid development of the chemical biology field and the emergence of a large number of chemical probes are expected to fuel innovations that will be essential for finding novel target drugs. By integrating new developments in chemical biology and probe discovery into drug discovery, ACCHTS would be in a unique position to catalyze the discovery and development of the next generation of efficacious and safe therapeutic agents.