Core 2: Medicinal Chemistry and Pharmacokinetics Core

Ohio State University, Columbus OH

Investigators

Linked publications & trials

Abstract

PROJECT SUMMARY – MEDICINAL CHEMISTRY AND PHARMACOKINETICS CORE (CORE 2) The primary goals of Core 2, to be carried out at The Ohio State University (OSU), are to support the discovery, characterization and optimization of novel anticancer agents through their synthesis, structural modification, and scale up, and the evaluation of pharmacokinetic (PK) properties of newly discovered and established lead compounds that demonstrate promising biological activity. Another Core 2 objective will focus on the use of a zebrafish model to assess compound activity and toxicity. The work done in the Core blends elements of organic chemistry, medicinal chemistry, pharmacology, and pharmaceutics to facilitate a thorough understanding of the chemical and biological properties of compounds in development. A wide array of synthetic methods will be used to tackle structural challenges associated with diverse natural scaffolds and to modify or introduce functionality capable of modulating physicochemical properties Since its inception, Core 2 has been very successful at supporting the isolation, identification, and development of a wide variety of structurally distinct natural products from Projects 1-3. The Core has been well integrated into the program, as evidenced by ongoing work in active collaboration with all three of the Projects and Core 1. Historically, these projects are highlighted by work on the phyllanthusmins and rocaglamides with Project 1 (OSU), scytonemide and the calthrixamides with Project 2 [University of Illinois at Chicago (UIC)], and the verticillins and eupenifeldin with Project 3 [University of North Carolina-Greensboro (UNCG)]. In addition, all new compounds synthesized for biological screening as a part of this project are sent to Core 1 (UIC). The medicinal chemistry and PK components of Core 2 have a common purpose of understanding and increasing the drug-like properties of the natural product lead compounds isolated and characterized in Projects 1-3. These two components are combined into a single core to enhance our efficiency in advancing newly discovered chemical entities toward potential application in biological systems, either as probes or therapeutic agents, in partnership with Core 1. The Core will be led by Drs. James R. Fuchs and Mitchell A. Phelps, who both have a strong history of collaboration with the senior investigators of the projects and bring experience in drug development from the Medicinal Chemistry and Pharmacokinetic (PK) perspectives, respectively. In addition to Drs. Fuchs and Phelps, Core 2 benefits from the academic and industrial expertise of Dr. Christopher Coss. He is also a member of the OSU Drug Discovery Institute and will utilize his experience in evaluating various leads for development through medicinal chemistry or PK efforts. Dr. Esperanza Carcache de Blanco brings expertise to the Core in the use of zebrafish models to assess drug activity and toxicity. Core 2 will make use of numerous drug development strategies and assays to advance natural products and their derivatives identified as a part of this project. The prioritization of compounds arising from Projects 1-3 for study in Core 2 will be made as a collective decision of the program project senior investigators.