Camptothecin Analogs for Cancer Therapy

用于癌症治疗的喜树碱类似物

• 批准号: 7326586
• 负责人: Lee ROY MORGAN
• 金额: $ 15.89万
• 依托单位: DEKK-TEC, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-27 至 2008-09-26
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7326586
• 关键词: Aminocamptothecin; Biological Assay; Camptothecin; Camptothecin Analogue; Characteristics; Childhood; Development; Dipeptides; Drug Kinetics; Hypoxia; In Vitro; Institutes; Lactones; Malignant Neoplasms; Mitochondrial Carnitine Palmitoyltransferase Pathway; Modeling; Neuroblastoma; Phase; Phase I Clinical Trials; Prodrugs; Protocols documentation; Research; Research Institute; Screening procedure; Tissues; Universities; Vascular blood supply; Water; Xenograft procedure; analog; cancer therapy; design; in vivo; novel; pre-clinical; preclinical study; tumor

DESCRIPTION (provided by applicant): 7-butyl-10-aminocamptothecin (BACPT) and its water-soluble dipeptide pro-drug, are novel camptothecins that were designed to be used in the treatment of childhood neuroblastoma. These CPT analogs are lactones that have increased activity in acidic hypoxia tissues, characteristic of fast growing cancers that characteristically out grow their blood supply. Preliminary in vitro and in vivo studies are presented to support documenting other tumor models that might be more sensitive. The specific objectives of this Phase I study will be to: 1. Synthesize 7-butyl-10-aminocamptothecin (BACPT) and its water-soluble dipeptide pro-drug, BACPTDP in 100 g quantities - sufficient for preclinical studies. 2. Verify the anticancer profile in xenograft studies. 3. Develop the analytical assays required to document purity and stability and develop/validate protocols for pharmacokinetic studies. Upon completion of these studies a Phase II application will be submitted for completion of preclinical studies required for IND submission. BACPT and BACPTDP are novel camptothecins that were originally designed at Duke University to be used in the treatment of childhood neuroblastoma. Subsequently, DEKK-TEC has partnered with Duke and Research Triangle Institute (RTI) to complete the pre-clinical development, prepare the IND and ready the products for a Phase 1 clinical trial. Prior to the latter, DEKK-TEC proposes screening the analogs in a wide spectrum of tumor models to insure the best cancer applications for the products.

描述（由申请人提供）：7-丁基-10-氨基喜树碱（BACPT）及其水溶性二肽前体药物是设计用于治疗儿童神经母细胞瘤的新型喜树碱。这些CPT类似物是在酸性缺氧组织中具有增加的活性的内酯，这是快速生长的癌症的特征，其特征是超出其血液供应。初步的体外和体内研究，以支持记录其他肿瘤模型，可能更敏感。本I期研究的具体目标是：1.合成7-丁基-10-氨基喜树碱（BACPT）及其水溶性二肽前药BACPTDP，用量为100 g-足以进行临床前研究。2.验证异种移植研究中的抗癌特征。3.开发记录纯度和稳定性所需的分析测定，并开发/验证药代动力学研究方案。完成这些研究后，将提交II期申请，以完成IND提交所需的临床前研究。BACPT和BACPTDP是新型喜树碱，最初由杜克大学设计用于治疗儿童神经母细胞瘤。随后，DEKK-TEC与杜克和三角研究所（RTI）合作，完成临床前开发，准备IND并为1期临床试验做好准备。在后者之前，DEKK-TEC建议在广泛的肿瘤模型中筛选类似物，以确保产品的最佳癌症应用。

项目成果

The Valley of Death in anticancer drug development: a reassessment.

• DOI: 10.1016/j.tips.2012.02.001
• 发表时间: 2012-04
• 期刊: Trends in pharmacological sciences
• 影响因子: 13.8
• 作者: Adams DJ

BACPTDP: a water-soluble camptothecin pro-drug with enhanced activity in hypoxic/acidic tumors.

• DOI: 10.1007/s00280-010-1388-8
• 发表时间: 2011-04
• 期刊: CANCER CHEMOTHERAPY AND PHARMACOLOGY
• 影响因子: 3
• 作者: Adams, David J.;Waud, William R.;Wani, Mansukh C.;Manikumar, Govindarajan;Flowers, James L.;Driscoll, Timothy A.;Morgan, Lee Roy
• 通讯作者: Morgan, Lee Roy