Preclinical Pharmacological Studies of Antitumor and Other Therapeutic Agents

该合同（梅奥诊所）为NCI发展治疗项目选择的候选治疗药物进行临床前药理学、药代动力学和代谢研究提供了资源。所选择的大多数化合物是潜在的抗癌剂（包括那些与孤儿癌症相关的化合物），但有些化合物是广泛流行和孤儿人类疾病的推定治疗药物。根据本合同选择用于研究的化合物可能来自各种同行评议的外部来源，例如癌症治疗药物开发小组（DDG）部门用于潜在的NCI研究新药（IND）申请，以及快速访问干预开发（RAID）和快速访问NCI发现资源（R* a *N*D）计划用于研究人员持有的IND。此外，开发项目也来自其他管道，如NCI临床显像剂和增强剂开发（DCIDE）计划，NIDDK 1型糖尿病RAID计划和NIH路线图RAID计划（为许多治疗类别的候选药物开发提供支持）。NCI的校内项目是研究抗癌化合物的一个来源。

This contract (Mayo Clinics) provides a resource for conducting preclinical pharmacology, pharmacokinetic, and metabolism studies with candidate therapeutic agents selected for development by the Developmental Therapeutics Program, NCI. Most of the compounds selected are potential anticancer agents (including those relevant to orphan cancers), but some are putative therapeutics for a wide range of prevalent and orphan human diseases. Compounds selected for study under this contract may arise from a variety of peer-reviewed extramural sources such as the Division of Cancer Treatment Drug Development Group (DDG) for potential NCI-held Investigational New Drug (IND) applications and the Rapid Access to Intervention Development (RAID) and Rapid Access to NCI Discovery Resources (R*A*N*D) Programs for investigator-held INDs. In addition, development projects also arise from other pipelines such as the NCI Development of Clinical Imaging Agents and Enhancers (DCIDE) program, the NIDDK Type-1 Diabetes RAID program, and the NIH Roadmap RAID Program (which provides support for development of candidate agents in many therapeutic categories). The NCI intramural program is a source of anticancer compounds for study. Work carried out under the contract may include: (1) development of analytical methods to quantify compounds in plasma, urine, and other biological matrices at levels corresponding to the expected therapeutic and/or toxic range; (2) plasma stability and protein binding studies, which are conducted at an early stage of compound development to ensure proper sample handling and to aid in the interpretation of animal studies; (3) pharmacokinetic characterization following administration to animals by various routes and schedules, including a determination of oral bioavailability where appropriate; (4) quantification and identification of drug metabolites generated in vivo and in various in vitro systems (e.g., S9 fractions, microsomes, hepatocytes, P450 isoforms, liver slices); and (5) assessment of pharmacodynamic effects in tumor or surrogate tissues and correlation of these effects with drug levels and/or total drug exposures. It is anticipated that the data obtained from these pharmacokinetic investigations will be useful in the design of preclinical efficacy and toxicology studies and Phase I clinical trials of selected agents. Technical reports submitted by the contractors will be included in INDs submitted to the FDA by the NCI or other institutions.