CRPC一流药物的靶向纳米给药系统：PK/PD评估和联合治疗-猫眼课题宝

CRPC一流药物的靶向纳米给药系统：PK/PD评估和联合治疗

批准号：

10676841

负责人：

Huan Xie

金额：

$17.05万

依托单位：

TEXAS SOUTHERN UNIVERSITY

依托单位国家：

美国

项目类别：

财政年份：

1986

资助国家：

美国

项目状态：

未结题

起止时间：

1986-09-30 至 2025-05-31

来源：

https://reporter.nih.gov/project-details/10676841

关键词：

Address Adverse reactions Affinity African American African American population Agreement Androgen Antagonists Androgen Receptor Androgens Animal Model Antigen Targeting Area Award Binding Biological Availability CWR22Rv1 Caco-2 Cells Cancer Etiology Cancer Patient Cell Culture Techniques Cell model Cessation of life Characteristics Chemosensitization Clinical Data Clinical Research Clinical Trials Collaborations Combined Modality Therapy Communities Data Disease Dose Drug Delivery Systems Drug Receptors Drug Targeting Drug or chemical Tissue Distribution Environment Enzymes Evaluation FOLH1 gene Folic Acid Food Formulation Fostering Future Gene Expression Genetically Engineered Mouse Goals Hormones Incidence Institution Intestines Intravenous Investigational Drugs Investigational New Drug Application Legal patent Liposomes Magic Malignant neoplasm of prostate Marketing Mediating Medical Membrane Metabolism Minority Health Research Modeling Monitor Morphology New Drug Approvals Outcome Particle Size Pathway interactions Patients Perfusion Pharmaceutical Preparations Pharmacologic Substance Polymers Primates Publications Race Rattus Reaction Receptor Signaling Recurrence Regimen Research Research Infrastructure Role Series Site Solid Statistical Data Interpretation Surface Tacrolimus Binding Proteins Techniques Texas Therapeutic Training United States Universities Xenograft Model Xenograft procedure absorption advanced prostate cancer antitumor effect castration resistant prostate cancer chemotherapy clinical application community engagement deprivation docetaxel drug candidate enzalutamide experimental study fighting first-in-human in vivo indexing intravenous administration lipid nanoparticle male men minority student mortality mouse model nanodrug new therapeutic target novel novel strategies novel therapeutics overexpression pharmacodynamic model pharmacokinetics and pharmacodynamics preclinical study prostate cancer cell prostate cancer cell line response standard care success synergism tacrolimus binding protein 4 targeted treatment therapeutic development tumor tumor growth tumor xenograft zeta potential

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中文摘要

翻译

项目总结前列腺癌(PCA)是美国男性癌症死亡的第二大原因，它是在非裔美国男性中更为常见。尽管最初对雄激素剥夺或抗- 雄激素药物治疗后，肿瘤无一例外地复发发展为致死性去势耐药前列腺癌(CRPC)。目前，可用于CRPC的治疗方案，包括黄金标准化疗多西紫杉醇，有只取得了有限的成功。52 kDa FK506结合蛋白(FKBP52)是一种很有前途的新策略有针对性的治疗开发。MJC13和GMC1，两种专门抑制FKBP52的一流药物- 德克萨斯大学埃尔帕索分校的考克斯博士发现了AR信号的中介增强。由德克萨斯南方大学的谢博士进一步开发。CRPC观察到的激动人心的抗肿瘤效果异种移植动物模型鼓励我们进一步开发新的靶向纳米药物传递系统(NDDS) 将MJC13和GMC1特异性地输送到肿瘤部位，然后稳定地释放药物，以促进协同作用多西紫杉醇治疗慢性前列腺癌的疗效观察我们的目标是开发叶酸(FA)偶联的MJC13和GMC1的NDDS，用于特异性的肿瘤靶向，高有效率和低脱靶不良反应；进行全面的体内药代动力学和 MJC13和GMC1最佳非脱氧核糖核酸的药效学评价 MJC13、GMC1和多西紫杉醇与市场上销售的抗AR药物苯扎鲁胺进行比较。我们将使用各种技术，大鼠、肿瘤移植小鼠模型和基因工程小鼠模型进行这些实验是与TSU和其他机构的专家合作进行的。该项目将寻求CBMHR行政核心的支持和评估，将大量利用研究基础设施核心进行研究，并将通过以下方式传播本项目的研究成果通过我们的社区参与核心(CEC)的支持，支持不同的TSU社区。它将进一步增强 RCMI机构在生物医学和少数族裔健康研究领域的声望。成功地执行了这项研究将为慢性前列腺癌患者带来潜在的高级治疗。

英文摘要

PROJECT SUMMARY Prostate cancer (PCa) is the second leading cause of cancer death in the United States among men and it is more common in African American males. Despite initial good responses to androgen deprivation or anti- androgen drugs, tumors invariably recur and develop into lethal castration resistant prostate cancer (CRPC). Currently, the available therapeutic options for CRPC, including the gold standard chemotherapy docetaxel, have only met with limited success. The 52 kDa FK506 binding protein (FKBP52) is a promising strategy for novel targeted therapeutic development. MJC13 and GMC1, two first-in-class drugs that specifically inhibit FKBP52- mediated potentiation of AR signaling, have been discovered by Dr. Cox at University of Texas at El Paso and further developed by Dr. Xie at Texas Southern University. The exciting anti-tumor efficacy observed in CRPC xenograft animal models encourage us to further develop novel targeted nano-drug delivery systems (NDDS) that specifically deliver MJC13 and GMC1 to the tumor site then steadily release the drug to facilitate synergistic effect with docetaxel to treat CRPC. Our aims are to develop folic acid (FA)-conjugated NDDS of MJC13 and GMC1 for specific tumor targeting, high efficacy and low off-target adverse reactions; to perform comprehensive in vivo pharmacokinetic and pharmacodynamic evaluations on the optimal NDDS of MJC13 and GMC1; to investigate combination therapy of MJC13 and GMC1 and docetaxel in comparison to the marketed anti-AR drug enzalutamide. We will use various techniques, rats, tumor xenograft mouse models and genetically engineered mouse models to conduct those experiments in collaboration with experts at TSU and other institutions. This project will seek support and evaluation from the CBMHR Administrative Core, will heavily utilize the Research Infrastructure Core to perform studies, and will disseminate the research findings from this project with various TSU communities via support from our Community Engagement Core (CEC). It will further enhance RCMI institutions’ prestige in the areas of biomedical and minority health research. The successful execution of this research will result potential advanced treatment for CRPC patients.

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