DESIGN OF 2-METHOXYESTRADIOL PRO-DRUG AND EVALUATION OF ITS ANTICANCER POTENTIAL

2-甲氧基雌二醇前药的设计及其抗癌潜力评价

• 批准号: 7959407
• 负责人: SUMAN KAMBHAMPATI
• 金额: $ 4.53万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959407
• 关键词: 2-methoxyestradiol; Address; Adverse effects; Animal Model; Biological Factors; Biological Models; Blood; Cancer Center; Cell Death; Chemical Structure; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Drug Evaluation; Drug Formulations; Effectiveness; Estradiol; Estrogens; Funding; Grant; Growth; Institution; Laboratories; Laboratory Study; Liver; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Mus; Patients; Pharmaceutical Preparations; Prodrugs; Research; Research Personnel; Resources; Solid Neoplasm; Source; Stomach; Therapeutic; United States National Institutes of Health; cancer cell; cancer therapy; cancer type; capsule; design; malignant breast neoplasm

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 2-Methoxyestradiol (2-ME2) is a natural product of the estrogen, estradiol. Recent laboratory studies suggest that 2-ME2 is an effective cancer therapy, decreasing growth and causing cancer cell death in multiple types of cancer. Because of these encouraging results in the laboratory, 2-ME2 was given orally (capsule form) in clinical trials involving patients with solid tumors, breast cancer and prostate cancer. One of the consistent objectives in all three studies included measuring 2-ME2 blood levels. Generally, 2-ME2 was noted to be well-tolerated with only limited side effects. However, in the majority of the patients, blood levels of 2-ME2 were low suggesting that the drug was not getting absorbed by the stomach and/or was being quickly destroyed by the liver and, therefore, was not adequately reaching the cancer in amounts to be effective. To address this problem, in our study we have proposed two specific aims. In specific aim 1, we will design new a formulation (change in the chemical structure) of 2-ME2 which will not be immediately inactivated within the body, and, therefore, will be better able to reach the cancer target. In specific aim 2, using a cancer mouse animal model system we will examine the blood levels and effectiveness of the new 2-ME2 and we will compare these results to the unaltered 2-ME2. If successful, the results of these studies would most definitively act as a forerunner to design new clinical trials with this new formulation and help identify a new treatment against a wide array of cancers.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 2-甲氧基雌二醇（2-ME 2）是雌激素雌二醇的天然产物。最近的实验室研究表明，2-ME 2是一种有效的癌症疗法，在多种类型的癌症中降低生长并导致癌细胞死亡。由于这些令人鼓舞的实验室结果，2-ME 2在涉及实体瘤、乳腺癌和前列腺癌患者的临床试验中口服（胶囊形式）。所有三项研究的一致目标之一包括测量2-ME 2血液水平。一般来说，2-ME 2被认为是耐受良好的，只有有限的副作用。然而，在大多数患者中，2-ME 2的血液水平较低，这表明药物没有被胃吸收和/或被肝脏迅速破坏，因此，没有充分达到有效的癌症量。为了解决这个问题，我们在研究中提出了两个具体目标。在具体目标1中，我们将设计新的2-ME 2制剂（化学结构的改变），其不会在体内立即失活，因此能够更好地达到癌症靶点。在具体目标2中，使用癌症小鼠动物模型系统，我们将检查新2-ME 2的血液水平和有效性，并将这些结果与未改变的2-ME 2进行比较。如果成功的话，这些研究的结果将最明确地成为用这种新配方设计新的临床试验的先驱，并帮助确定一种针对各种癌症的新疗法。