Improving Efficacy of RNase Cancer Therapy by Pharmacokinetics

通过药代动力学提高 RNase 癌症治疗的疗效

• 批准号: 7270289
• 负责人: MARK N SHAHAN
• 金额: $ 12.56万
• 依托单位: QUINTESSENCE BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-27 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7270289
• 关键词: A549; Adverse effects; Amino Acid Substitution; Amino Acids; Animals; Antineoplastic Agents; Binding; Biological Assay; Body Weight; Cancer Patient; Cells; Cisplatin; Cisplatin/Docetaxel; Clinic; Clinical; Clinical Chemistry; Clinical Research; Clinical Trials; Commit; Complex; Cysteine; DU145; Detection; Development; Dose; Drug Kinetics; Endoribonucleases; Ensure; Enzyme-Linked Immunosorbent Assay; Enzymes; Erlotinib/Gemcitabine; Exhibits; Family suidae; Financial Support; Fluorouracil; Generations; Goals; Growth; Half-Life; High Pressure Liquid Chromatography; Hour; Human; In Vitro; Kidney; Lead; Liver; Lung; Malignant Neoplasms; Malignant neoplasm of pancreas; Malignant neoplasm of prostate; Marketing; Mass Spectrum Analysis; Methods; Microtubules; Modeling; Molecular Weight; Mus; Names; New Agents; Non-Small-Cell Lung Carcinoma; Nude Mice; Outcome; Ovarian; Pancreas; Pancreatic ribonuclease; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Physicians; Plasma; Polyethylene Glycols; Positioning Attribute; Process; Production; Program Development; Property; Prostate; Proteins; RNA; Reagent; Recombinants; Relative (related person); Resources; Ribonucleases; Safety; Sampling; Schedule; Series; Serine; Serum; Site; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Sodium Dodecyl Sulfate-PAGE; Structure; Sulfhydryl Compounds; Testing; Therapeutic; Toxic effect; Treatment Protocols; Tumor Cell Line; United States Food and Drug Administration; Variant; Work; Xenograft Model; Xenograft procedure; abstracting; base; cancer cell; cancer therapy; cancer type; commercial application; commercialization; compliance behavior; cost; drug efficacy; falls; genotoxicity; immunogenicity; improved; in vivo; inhibitor/antagonist; interest; macromolecule; malignant breast neoplasm; next generation; novel; programs; research study; small molecule; therapeutic protein; tool; tumor; tumor growth

DESCRIPTION (provided by applicant): 6. Project Summary Abstract The goal of this project is to develop a safe yet potent drug utilizing an EVade(tm) Ribonuclease. The EVade(tm) Ribonucleases are recombinant variants of mammalian enzymes that are effective in mouse xenograft models of multiple cancer types without exhibiting significant toxicity. While they are effective, Quintessence is interested in increasing the potency of the EVade(tm) Ribonucleases to improve clinical outcome. Many of the FDA approved cancer therapies work by very similar mechanisms, including genotoxicity, anti-metabolite and microtubule binding. Newer, targeted therapies are being developed, with a few of these drugs already on the market. We believe an agent with a novel mechanism of action and mild side effect profile, such as an EVade(tm) Ribonuclease, is a strong candidate for cancer therapy. We will change the pharmacokinetic profile of the EVade(tm) Ribonucleases. The EVade(tm) RNase and macromolecules for conjugation were selected because they have shown efficacy in vivo. The initial experiments will produce and characterize the next generation EVade(tm) RNases while the second round will determine the in vivo effects of combining the conjugated EVade(tm) Ribonucleases at various concentrations. The ultimate goal of this project is to develop a new safe AND effective tool for physicians to treat patients with cancer.

描述(由申请人提供)：6.项目摘要本项目的目标是开发一种利用evade(Tm)核糖核酸酶的安全而有效的药物。EVADE(Tm)核糖核酸酶是哺乳动物酶的重组变体，在多种癌症类型的小鼠异种移植模型中有效，且没有明显毒性。虽然它们是有效的，但QuintEssence对提高evade(Tm)核糖核酸酶的效力以改善临床结果感兴趣。FDA批准的许多癌症治疗方法的作用机制非常相似，包括遗传毒性、抗代谢物和微管结合。更新的靶向疗法正在开发中，其中几种药物已经上市。我们认为，具有新的作用机制和轻微副作用的药物，如evade(Tm)核糖核酸酶，是癌症治疗的有力候选者。我们将改变evade(Tm)核糖核酸酶的药代动力学曲线。选择了evade(Tm)核糖核酸酶和大分子进行偶联，因为它们在体内表现出了有效性。最初的实验将产生和表征下一代EVADE(Tm)核糖核酸酶，而第二轮将确定不同浓度的结合EVADE(Tm)核糖核酸酶的体内效应。该项目的最终目标是为医生开发一种新的安全有效的工具来治疗癌症患者。