P07-22

Drug discovery research utilizing BROOD: A Fragment Replacement and Molecular Design tool

KOSUKE MINAGAWA *SHUNYA MAKINOKAN SHIRAISHI

Modarity Research Laboratories 1, Daiichi Sankyo Co., Ltd.
( * E-mail: kosuke.minagawa@daiichisankyo.com )

BROOD, a tool developed by OpenEye, proposes structures that have similar shape and electrostatic properties to a specific substructure based on information from the ChEMBL database. It is a useful tool for exploring the chemical and property space around hit or lead compounds.
Since launching the "Data-Driven Drug Discovery" (D4) strategy in 2018, we have been actively working on improving the operational efficiency of drug discovery research through information extraction from public data and the utilization of cheminformatics methods [1]. As part of these efforts, we have incorporated structure generation into the drug discovery process and shared ideas with medicinal chemists.
The process from BROOD structure generation to actual compound synthesis varies depending on the project's circumstances. Specifically, factors such as the presence of target protein structure information, the structural transformation site (side chain or skeleton), or whether overtake approach or not. Depending on these differences, it is possible to propose adequate compounds for medicinal chemists to find compounds to be synthesized easily and quickly.
In this presentation, we introduce various scenarios of the process from structure generation to actual compound synthesis.

References
[1] Ryo Kunimoto, Jürgen Bajorath, Kazumasa Aoki, From traditional to data-driven medicinal chemistry: A case study, Drug Discovery Today, 2022, 27, 2065.