MODEL PARAMETERS FOR ANTHRACYCLINE DRUGS

蒽环类药物的模型参数

• 批准号: 3166576
• 负责人: HERBERT S SCHWARTZ
• 金额: $ 8.58万
• 依托单位: ROSWELL PARK CANCER INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-01-01 至 1985-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3166576
• 关键词: DNA directed DNA polymerase; DNA repair; adenosinetriphosphatase; anthracyclines; cyclic AMP; cyclic GMP; daunorubicin; doxorubicin; drug adverse effect; drug metabolism; enzyme induction /repression; human therapy evaluation; human tissue; hydroxyapatites; macromolecule; mathematical model; microsomes; mitochondria; myocardium disorder; neoplasm /cancer pharmacology; neoplastic cell; phospholipids; thin layer chromatography; thymidine; tissue /cell culture

Some of the drugs that interact with DNA are among our most useful drugs in the treatment of neoplastic diseases. The agents and many derivatives bind to DNA and produce strand scission. We developed a model to evaluate parameters of their actions and now use the model to study drug metabolism and activation in tumors and in tissues that are selectively intoxicated. Studies are carried out with tumor cells and membranes and animal mitochondria, microsomes, and enzymes to define the systems of activation and to evaluate the means for control of their toxicity. Studies with phospholipids and enzymes indicate biotransformation of the agents to forms that may be proximal to the final reactants which bind covalently to macromolecules. Pharmacokinetic studies in progress are aimed to relate in vitro drug metabolism and drug activation to biological activity of the agents.

一些与 DNA 相互作用的药物是我们在该领域最有用的药物之一。 治疗肿瘤疾病。 这些试剂和许多衍生物与 DNA 结合 并产生断链。 我们开发了一个模型来评估参数 他们的行为，现在使用该模型来研究药物代谢和激活 肿瘤和选择性中毒的组织中。 研究正在进行 与肿瘤细胞和膜以及动物线粒体、微粒体和酶 定义激活系统并评估控制手段 他们的毒性。 对磷脂和酶的研究表明 将药剂生物转化为可能最接近最终形式的形式 与大分子共价结合的反应物。 药代动力学研究 进展旨在将体外药物代谢和药物激活与 药剂的生物活性。