Translational Research Core

转化研究核心

• 批准号: 10845860
• 负责人: Colin Osborne
• 金额: $ 351.83万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 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/10845860
• 关键词: Binding Proteins; Biological Assay; Biophysics; Cardiovascular system; Central Nervous System; Clinic; Clinical; Clinical Pharmacology; Data; Data Scientist; Development; Dose; Drug Delivery Systems; Drug Interactions; Drug Kinetics; Ensure; Enzymes; Excretory function; Formulation; Funding; Guidelines; Hazard Identification; Human; In Vitro; Knowledge; Machine Learning; Metabolic Biotransformation; Metabolism; Modeling; Nature; Organ; Pathology; Patients; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology; Pharmacology and Toxicology; Phase; Phototoxicity; Plasma Proteins; Play; Process; Qualifying; Regimen; Role; Safety; Science; Specialist; Techniques; Technology; Therapeutic; Toxic effect; Toxicokinetics; Toxicology; Translational Research; Translations; Work; absorption; candidate selection; clinical candidate; clinical development; design; drug candidate; drug discovery; drug disposition; drug metabolism; first-in-human; genotoxicity; in silico; in vivo; in vivo Model; models and simulation; multidisciplinary; pandemic preparedness; patient safety; pharmacokinetics and pharmacodynamics; pre-clinical; preclinical development; preclinical safety; safety assessment; screening; small molecule; success; translational model

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-摘要 翻译研究核心将支持项目团队选择和推进有前途的临床候选人 通过在体外和体内进行必需的ADMET(吸收、分布、代谢、 排泄物和毒物学)研究。这将主要由药动学的专家团队实现。 科学(PKS)和临床前安全(PCS)设在诺华。PKS 团队将在体外和体内提供 吸收、分布、代谢和排泄(ADME)数据。为了实现这一目标，他们将在 深入了解临床前药代动力学、药物代谢和临床药理学知识 化合物设计、配方开发和最佳人体给药方案。具体地说，翻译 Research Core将组建一支跨学科团队(包括生物转化、转运体、 药物相互作用、血浆蛋白结合、体内模型等)，以帮助选择和优化潜力 药物递送的候选人。PKS功能还将进行毒物动力学研究，以计算治疗 并确定首例人体研究的安全起始剂量。此外，它还将部署尖端设备 预测人体有效暴露的学习、转换、生物物理和其他建模技术 基于可获得的体外和体内药代动力学、药理学和毒理学数据。PCS团队将 提供从早期发现到注册试验的体外和体内临床前安全性数据，并向患者保证 安全完全符合严格监管机构的要求。PC专家将进行广泛的 针对特定毒理学的体外和体内探索性/机械性和调节性毒理学研究 每个项目的需求，最终组装一个完整的监管毒理学包，以确定危险和 建立安全边际。该小组将进行非GLP筛查分析和GLP研究，以确定 发展候选(DC)选择的遗传毒性、光毒性和安全药理学责任 作为IND应用程序的一部分。总而言之，翻译研究核心将发挥关键作用 通过帮助评估、区分并最终将药物发现和转化应用于临床 选择最好的分子。