Camptothecin Analogs for Cancer Therapy

描述(申请人提供)：7-丁基-10-氨基喜树碱(BACPT)及其水溶性二肽前药，是用于治疗儿童神经母细胞瘤的新型喜树碱。这些CPT类似物是内酯类化合物，在酸性缺氧组织中活性增加，这是快速生长的癌症的特征，其特征是血液供应不足。初步的体外和体内研究被提出，以支持记录其他可能更敏感的肿瘤模型。这一阶段研究的具体目标是：1.合成100g的7-丁基-10-氨基喜树碱(BACPT)及其水溶性二肽前药BACPTDP，足以进行临床前研究。2.在异种移植研究中验证抗癌特性。3.开发记录纯度和稳定性所需的分析分析方法，并制定/验证药代动力学研究方案。在这些研究完成后，将提交第二阶段申请，以完成IND提交所需的临床前研究。BACPT和BACPTDP是杜克大学最初设计用于治疗儿童神经母细胞瘤的新型喜树碱。随后，Dekk-TEC与杜克大学三角研究所(RTI)合作，完成临床前开发，准备IND，并为产品的第一阶段临床试验做好准备。在后者之前，Dekk-TEC建议在广泛的肿瘤模型中筛选类似物，以确保产品在癌症中的最佳应用。

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.