Core--Drug Development

核心--药物开发

• 批准号: 6991771
• 负责人: STEVEN P STRATTON
• 金额: $ 20.82万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6991771
• 关键词: antineoplastics; biomedical facility; chemoprevention; drug design /synthesis /production; drug screening /evaluation; prodrugs; skin neoplasms; topical drug application

DESCRIPTION (provided by applicant): Molecularly targeted agents against UV signal transduction pathways can be incorporated into topical formulations engineered to optimize delivery to skin and maximize the probability of success in preclinical and clinical evaluation. Long-term preclinical carcinogenesis studies in Projects I-III and clinical trials in Project IV cannot be initiated without the preparation and proper testing of well-characterized, stable formulations of topical agents. The Drug Development Core provides this crucial service to the Program Project. The objective of the Drug Development Core is to efficiently design, prepare, test, and provide pharmaceutically suitable topical formulations of new skin cancer chemopreventive agents to Program Project investigators and to provide regulatory support for clinical development of candidates that show promise. An innovative addition to this competing application is the ability and expertise to synthesize chemical entities as prodrugs in order to enhance solubility, absorption, and delivery to the epidermis. This objective will be accomplished by the following Specific Aims: 1) To prepare stable formulations of promising new agents that can be effectively delivered to the epidermis following topical application, 2) To prepare batch formulations for long-term carcinogenesis studies in vivo and perform necessary preclinical toxicology, pharmacokinetic, and stability studies, and 3) To coordinate and prepare Investigational New Drug (IND) applications for FDA approval, and supervise production and distribution of clinicalgrade supply for human trials in Project IV. The Drug Development Core will oversee all aspects of topical agent preparation, formulation, and supply for each of the Projects. Quality control and assurance methods developed by the Drug Development Core in consultation with the Biometry Core will ensure regulatory compliance and enhance efficiency. The Drug Development Core will work closely with each Project to provide necessary and appropriate topical formulations for each stage of mechanistic and efficacy studies in vivo. This will allow us to circumvent problems with epidermal delivery that normally hinder development of otherwise promising topical agents, and optimize the crucial selection criteria for advancement of new agents to clinical testing. This will greatly enhance our ability to translate basic science discoveries into new skin cancer chemopreventive drugs.

描述（由申请人提供）：针对紫外线信号转导途径的分子靶向药物可以纳入局部制剂中，以优化皮肤递送并最大限度地提高临床前和临床评估的成功概率。如果没有制备和适当测试特征良好、稳定的外用药物制剂，就无法启动项目 I-III 中的长期临床前致癌研究和项目 IV 中的临床试验。药物开发核心为该计划项目提供这一重要服务。药物开发核心的目标是有效地设计、制备、测试并向项目研究人员提供新皮肤癌化学预防剂的药学上合适的局部制剂，并为有前景的候选药物的临床开发提供监管支持。这一竞争性应用的一个创新补充是合成化学实体作为前药的能力和专业知识，以增强溶解度、吸收和向表皮的递送。这一目标将通过以下具体目标来实现：1) 制备有前途的新药的稳定制剂，在局部应用后可以有效地递送至表皮，2) 为体内长期致癌研究制备批量制剂，并进行必要的临床前毒理学、药代动力学和稳定性研究，以及 3) 协调和准备 FDA 批准的研究性新药 (IND) 申请，并监督生产和分销 临床级 为项目 IV 的人体试验提供供应。药物开发核心将监督各个方面 每个项目的外用制剂的制备、配制和供应。质量控制和 药物开发核心与生物测定核心协商制定的保证方法将确保合规性并提高效率。药物开发核心将与每个项目密切合作，为体内机制和功效研究的每个阶段提供必要和适当的局部制剂。这将使我们能够避免表皮递送问题，这些问题通常会阻碍其他有前途的外用药物的开发，并优化新药物进入临床测试的关键选择标准。这将大大增强我们将基础科学发现转化为新的皮肤癌化学预防药物的能力。