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Pharmaceutical Sciences Core

制药科学核心

基本信息

批准号：
10241497
负责人：
Vincent Jo Davisson
金额：
$ 36.42万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10241497
关键词：
Age Animal Model Biological Availability Brain Characteristics Chemicals Chemistry Cyanides Decision Making Development Dose Drug Kinetics Ensure Equilibrium Evaluation Excipients Family suidae Formulation Goals In Vitro Investigational Drugs Lead Mammals Metabolic Metabolism Methods Modeling Organ Oryctolagus cuniculus Peripheral Permeability Pharmaceutical Chemistry Pharmaceutical Technology Pharmacodynamics Pharmacologic Substance Pharmacology and Toxicology Pharmacy (field)Process Process Assessment Prodrugs Property Rattus Resources Risk Safety Science Site Staging Standardization Structure Testing Tissues Toxic effect Toxicology Translations Triage Universities Variant Zebrafish analog animal efficacy base candidate selection chemical association design drug development follow-up glyoxylate improved in vivo in vivo Model lead candidate lead optimization meetings metabolic phenotype mouse model novel porcine model pre-clinical programs screening solid state

项目摘要

Abstract: The goal of the Pharmaceutical Sciences Core (PSC) is to provide drug development capabilities needed by the Center to enable the rapid translation of new chemical entities (NCEs) useful for cyanide countermeasures. The approach will be to add both capacity and capabilities in pharmacokinetics, toxicology, medicinal chemistry, and formulation through a collaborative team lead by Drs. V. J. Davisson and Gregory Knipp at Purdue University. The U54 program currently is able to use unbiased screening approaches in zebrafish to identify new chemical entities that show protection against cyanide toxicities. From the programs, there is capacity to conduct hit follow-up chemistry to qualification of new hit chemotypes. The PSC will critically evaluate and prioritize lead candidate compounds and formulations while executing hit-to-lead development studies. A focus of the U54 program moving forward is to establish, in addition to traditional scavengers, new metabolic modulators for tissue and organ protection against cyanide toxicity. While feasibility for translation to animal models is being demonstrated with hit compounds, barriers in meeting the product concept for relevant threat scenarios are significant. The PSC will provide capabilities for standardized in vivo pharmacology and toxicology support, pharmacokinetic assessment, physicochemical and solid-state property assessment and selection, preclinical formulation support that will accelerate translation and fulfill the program deliverables. A lead candidate staging process will be implemented to a) improve processes for assessment of the hit-to-leads and interface with in vivo models, b) improve the capacity to select compounds for lead development from the discovery group, c) provide entrée to lead compound efficacy and safety evaluation in mammalian models. In doing so, the PSC will impact decision making and resource management to enhance pharmaceutical strategies (developability properties) to enable more efficient transition from zebrafish to mammals.

摘要：药学科学核心（PSC）的目标是提供药物开发能力