Compound Attrition at the Preclinical Phase
Cornelis E. C. A. Hop · 2015
Determining drug absorption, distribution, metabolism, and excretion (ADME) properties of drug candidates early on in the drug discovery process is critical for achieving drugs with optimal properties and, in particular, an acceptable dose and dosing regimen. This chapter addresses past, current, and future practices in the pharmaceutical and biotechnology industry and their impact on attrition. It includes more small-molecule examples than large-molecule examples, but many of the same principles apply. However, there are also distinct differences such as the optimization process and, consequently, the preclinical attrition. Currently, drug discovery usually begins with identification of the target of interest based on compelling preclinical and human genetic data. Covalent inhibitors have been around for a long time, and quite a few drugs bind covalently to their target of interest. There are two common approaches in drug discovery to guide design of compounds with superior potency: structure-based design and property-based design.