The 145th Annual Meeting of the Pharmaceutical Society of Japan (Fukuoka)

Organizer: HIROYUKI MIYACHI (drug discovery initiative, Tokyo Univ.), KATSUMI MAENAKA (Facul. Pharm. Sci., Hokkaido Univ. / Grad. Sch. Pharm. Sci., Kyushu Univ.)

In recent years, middle molecules have garnered attention as a new modality in drug discovery. From the perspective of practical research aimed at drug development, it is crucial to consider not only the previously recognized challenges of middle molecules, such as poor cell membrane permeability (i.e., low membrane permeability coefficient), but also the control of efflux via transporters from inside to outside the cell. However, practical research and development that addresses both of these aspects has been largely lacking. Therefore, this symposium will focus on these dual perspectives. Presentations will be made by a highly heterogeneous group of researchers, including organic chemists, biochemist, computational chemist, and structural biologist. They will discuss the synthesis of various natural middle molecule derivatives such as bottromycins, macrocyclic peptides, and etoposide derivatives, as well as measurements of passive diffusion rates and cell membrane permeability. Additionally, molecular dynamics simulations predicting membrane permeability processes and cryo-electron microscopy analyses will be presented. Through these discussions, we aim to enhance understanding of the importance of comprehensively evaluating activity, membrane permeability, and P-glycoprotein substrate characteristics in the selection of candidate middle molecule for development.