Core C – Drug Metabolism, Pharmacokinetics and Toxicology (DMPK/Tox)

核心 C — 药物代谢、药代动力学和毒理学 (DMPK/Tox)

• 批准号: 10513938
• 负责人: Alexander Kolykhalov
• 金额: $ 811.65万
• 依托单位: EMORY UNIVERSITY
• 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/10513938
• 关键词: Anabolism; Animals; Antiviral Therapy; Binding Proteins; Biological Assay; Biological Availability; Bone Marrow; COVID-19 treatment; Canis familiaris; Cardiotoxicity; Carrier Proteins; Cells; DNA Damage; Data; Development; Disease; Dose; Drug Interactions; Drug Kinetics; Drug or chemical Tissue Distribution; FDA Emergency Use Authorization; Follow-Up Studies; Fostering; Foundations; Hepatitis B Virus; In Vitro; Industry; Institutes; Liver Microsomes; Membrane Transport Proteins; Metabolic; Metabolism; Mitochondria; Modeling; Oral; Organ; Pathogenesis; Penetration; Permeability; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology; Phase; Phase II Clinical Trials; Plasma; Plasma Proteins; Play; Probability; Protocols documentation; Rattus; Reporting; Resources; Ribonucleosides; Ribonucleotides; Rodent; Role; SARS-CoV-2 infection; Safety; Scientist; Seasons; Secure; Series; Serum; Serum Proteins; Solubility; Testing; Therapeutic; Toxic effect; Toxicokinetics; Toxicology; Vendor; Virus Diseases; absorption; analog; animal efficacy; aqueous; base; chemical stability; design; drug candidate; drug development; drug discovery; drug metabolism; efficacy study; efficacy testing; experimental study; genotoxicity; in vitro Assay; in vivo; lead optimization; medical schools; metabolic profile; micronucleus; molnupiravir; operation; pre-clinical; process optimization; success; synergism; tripolyphosphate; uptake

Summary – Core C Core C will provide AC/DC Cores and Projects with the drug metabolism, pharmacokinetic and toxicology (DMPK/Tox) data that is required to guide lead optimization, tolerability, and pharmacodynamic profiling. Core C brings industry seasoned expertise and a successful track record of drug development as exemplified by the preclinical characterization of molnupiravir (under consideration for Emergency Use Authorization as a treatment for SARS-CoV-2 infections), and EIDD-2173 (currently in Phase 2 clinical trials for hepatitis B virus infections). All AC/DC DMPK/Tox operations have accordingly been centralized into Core C to provide the synergies realized by generating data that is crucial and applicable to multiple projects, and to avoid redundant studies. The solubility, stability cellular uptake and cellular metabolic profiles of validated hits and early leads will be determined to filter those with a low probability of success and to inform iterative discovery and optimization. Drug metabolism, pharmacokinetic and tissue distribution data will be provided to inform animal efficacy studies and lead optimization. Finally, the tolerability of late leads will be assessed with both in vitro assays and non- GLP dose range finding toxicokinetic studies.

总结 – 核心 C Core C将为AC/DC核心和项目提供药物代谢、药代动力学和毒理学研究 指导先导化合物优化、耐受性和药效学分析所需的 (DMPK/Tox) 数据。核 C 带来了行业经验丰富的专业知识和药物开发的成功记录，例如 molnupiravir 的临床前表征（正在考虑紧急使用授权作为一种治疗方法） 用于 SARS-CoV-2 感染）和 EIDD-2173（目前处于乙型肝炎病毒感染的 2 期临床试验中）。 所有 AC/DC DMPK/Tox 操作都相应地集中到 Core C 中，以提供实现的协同效应 通过生成关键且适用于多个项目的数据，并避免重复的研究。这 经验证的命中和早期先导化合物的溶解度、稳定性、细胞摄取和细胞代谢特征将 决心过滤那些成功概率较低的项目，并为迭代发现和优化提供信息。 将提供药物代谢、药代动力学和组织分布数据，为动物功效研究提供信息 和先导优化。最后，将通过体外试验和非试验来评估晚期导联的耐受性。 GLP 剂量范围寻找毒代动力学研究。