Translational Research Core

转化研究核心

基本信息

批准号：
10514151
负责人：
Colin Osborne
金额：
$ 688.95万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-16 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10514151
关键词：
Binding Proteins Biological Assay Biophysics Cardiovascular system Clinic Clinical Clinical Pharmacology Data Data Scientist Development Dose Drug Delivery Systems Drug Interactions Drug Kinetics Ensure Enzymes Excretory function Formulation Funding Guidelines Human In Vitro Knowledge Machine Learning Metabolic Biotransformation Metabolism Modeling Nature Neuraxis Organ Pathology Patients Pharmaceutical Preparations Pharmacodynamics Pharmacology Pharmacology and Toxicology Phase Phototoxicity Plasma Proteins Play Process Regimen Role Safety Science Specialist Techniques Technology Therapeutic Toxic effect Toxicokinetics Toxicology Translational Research Translations Ursidae Family Work absorption base candidate selection clinical candidate clinical development design drug candidate drug discovery drug disposition drug metabolism first-in-human genotoxicity hazard in silico in vivo in vivo Model models and simulation multidisciplinary pandemic preparedness patient safety pharmacokinetic model pharmacokinetics and pharmacodynamics pre-clinical preclinical development preclinical safety safety assessment screening small molecule success translational model

项目摘要

TRANSLATIONAL RESEARCH CORE – ABSTRACT The Translational Research Core will support Project Teams to select and advance promising clinical candidates by conducting essential in vitro and in vivo ADMET (absorption, distribution, metabolism, excretion and toxicology) studies. This will be achieved primarily by specialist teams in Pharmacokinetic Sciences (PKS) and Preclinical Safety (PCS) housed at Novartis. PKS teams will provide in vitro and in vivo absorption, distribution, metabolism, and excretion (ADME) data. To achieve this, they will contribute in depth knowledge of preclinical pharmacokinetics, drug metabolism, and clinical pharmacology to inform compound design, formulation development, and optimal human dosing regimens. Specifically, the Translational Research Core will bring to bear a cross-disciplinary team (including expertise in biotransformation, transporters, drug-drug interactions, plasma protein binding, in vivo models, and more) to help select and optimize potential candidates for drug delivery. The PKS function will also conduct toxicokinetics studies to calculate therapeutic margins and determine safe starting doses for first-in-human studies. Further, it will deploy cutting edge machine learning, translational, biophysical and other modelling techniques to predict human efficacious exposures based upon available in vitro and in vivo pharmacokinetics, pharmacology and toxicology data. PCS teams will provide in vitro and in vivo preclinical safety data from early discovery to registration trials and assure patient safety is fully compliant with requirements by stringent regulatory agencies. PCS specialists will conduct a wide range of in vitro and in vivo exploratory/mechanistic and regulatory toxicology studies tailored to the specific needs of each project, eventually assembling a complete regulatory toxicology package to identify hazards and establish safety margins. This group will conduct non-GLP screening assays and GLP studies to determine genotoxicity, phototoxicity, and safety pharmacology liabilities at the Development Candidate (DC) selection stage and as part of IND applications. In summary, the Translational Research Core will play a pivotal role in bridging drug discovery and translation to the clinic by helping evaluate, differentiate, and ultimately select the best molecules.

翻译研究核心核心核心核心核心翻译研究核心将支持项目团队选择有希望的候选候选adididididididates 通过在体外和体内进行必不可少毒理学和毒理学）研究将主要由药代动力学专业团队进行科学（PKS）和临床前安全（PC）位于诺华团队将在体外和体内提供吸收，分布，代谢和交换（ADME）数据。临床前药代动力学，药物代谢和临床药理学的深度知识复合设计，配方开发和最佳人类给药方案。研究核心将带来一个跨学科团队（包括生物转化，运输商，运输者，药物 - 药物相互作用，血浆蛋白结合，体内模型等）有助于选择和优化潜力药物递送的候选者。边缘并确定首先人类研究的安全起始剂量。学习，翻译，生物物理和其他建模技术，以预测人类有效的暴露根据可用的体外和体内药代动力学，药理学和毒理学数据提供从早期发现到注册试验的体外和体内临床前安全数据，并确保患者安全完全符合严格的监管机构的要求。量身定制的体外和体内探索/机械和调节毒理学研究范围每个项目的需求，最终组装一个完整的监管毒理学包，以确定危害和建立安全利润率。开发候选者（DC）选择的基因毒性，光毒性和安全药理学责任阶段和指示的一部分。通过帮助评估，区分并最终将药物发现和转化为诊所选择最佳分子。