Scientific Support Core: Pharmaceutics and Medicinal Chemistry Scientific Support Core Key Personnel: Patrick J. Sinko, Ph.D., Core Co-Lead, Co-Leader, Innovative Drug Delivery Team Ned D. Heindel, Ph.D., Core Co-Lead, Co-Leader, Scale-up and Manufacturing Support Team Christophe Guillon, Ph.D., Co-Leader, Scale-up and Manufacturing Support Team Laurie Joseph, Ph.D., Leader, Pre-clinical Formulations Team C. Jeffrey Lacey, Ph.D., Leader, Compound Library Support Team Zoltan Szekely, Ph.D., Co-Leader, Innovative Drug Delivery Team Core Summary/Abstract The Pharmaceutics and Medicinal Chemistry Scientific Support Core works closely with Center investigators within the Research and Development Projects and the Pharmacology and Drug Development Core to discover and optimize lead agents and prospective formulations/drug delivery systems (DDS) that can be used to treat vesicant poisoning, and to assist in their development into drug products for approval by the FDA. In order to rapidly translate mechanistic discoveries from the research projects to the clinic, our Center has identified drug products approved by the FDA for other therapeutic indications and has proposed their use for treating vesicant toxicity, a new indication. We currently have IND applications in process and are working with Center investigators to complete IND-enabling studies in support of Pre-IND FDA meetings. The Pre-clinical Formulations Focus Team works closely with the Pharmacology and Drug Development core and the Research project teams to produce stable preclinical formulations for initial efficacy and toxicological assessment. The Innovative Drug Delivery Focus Team is developing novel DDS in order to overcome biopharmaceutical barriers (e.g., protein instability, poor permeability, or high clearance) or physiochemical limitations such as poor aqueous solubility or instability. Analytical chemistry support is provided for stability studies on formulated Active Pharmaceutical Ingredients (APIs), metabolite identification, and pharmacokinetic, toxicokinetic and pharmacodynamics studies. The Compound Library Support Team is optimizing API compound classes with previously identified leads and new compound classes are in development. The Scale- up and Manufacturing Support Team assures the scalability of synthetic processes, process improvements, optimization of multi-step pathways, availability of clinical grade material and confirmation of the stated certificate of purity by Contract Manufacturing organizations. In order to promote a countermeasure API to full pre-IND status, the Medicinal Chemistry team works closely and iteratively with the research projects to determine the most efficacious therapeutic compounds and backup candidates. This Scientific Support core then develops the preclinical regimen specifications including dose required, dosing interval, and pharmacokinetics. Using these specifications, the Pharmaceutics team refines the DD platform technologies for the specific drug candidate and delivery specifications. In short, the development process is highly collaborative and iterative.
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