Abstract

Drug design and development requires collaboration among scientists with diverse expertise. In early-stage drug design, establishment of promising drug candidates requires integration of structure-based molecular design with biopharmaceutics and ADMET (absorption, distribution, metabolism, excretion, and toxicity) principles. Much of this work is increasingly computational. Thus, students in a drug design course should learn the basis for and effects of candidate small molecules binding to therapeutic targets and the importance of simultaneous understanding of ADMET characteristics that will largely determine if the molecule can achieve a therapeutically relevant concentration at the target site and become an orally deliverable drug. This second aspect of education in drug design has been relatively overlooked compared to structure-based design. Here, we describe a course using sophisticated simulation and modeling software, GastroPlus and ADMET Predictor, which are commonly used in the pharmaceutical industry. Our teaching approach has evolved over a decade in early graduate and advanced undergraduate settings. We use a combination of short lectures, software demonstration, and hands-on use, which allows students to “design a drug” with incorporation of structural and ADMET considerations. Student feedback indicated that the use of the software and the course design were helpful in enhancing their understanding of the importance of biopharmaceutics properties and ADMET in drug design. GastroPlus and ADMET Predictor have recently become more accessible to educators, and our experience using this software in an educational setting may be helpful for instructors who wish to develop a similar course.

By Rebecca M. Romero, Michael B. Bolger, Noam Morningstar-Kywi, and Ian S. Haworth