HTS enabled examination of drug combinations

HTS 能够检查药物组合

• 批准号: 9354986
• 负责人: Craig Thomas
• 金额: $ 14.73万
• 依托单位: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9354986
• 关键词: Adult T-Cell Leukemia/Lymphoma; B-Lymphocytes; Basic Science; Biological Assay; Caring; Clinical Trials; Combined Modality Therapy; Cyclophosphamide; Disease; Doxorubicin; Drug Combinations; Ebola virus; Epithelial; Evaluation; Hematologic Neoplasms; Human; Imagery; Immunotoxins; Informatics; Interleukin-2; Kyocristine; Malaria; Malignant Neoplasms; Methods; Non-Hodgkin' s Lymphoma; Outcome; Outcome Study; Pharmaceutical Preparations; Prednisone; Regimen; Research Personnel; Signal Pathway; Technology; Vincristine; base; cancer type; combat; combinatorial; inhibitor/antagonist; novel; novel drug combination; pre-clinical; research clinical testing; rituximab; screening

Matrix screening at NCATS aims to identify synergistic drug combinations for the treatment of multiple diseases using a quantitative high-throughput combinatorial screening platform. A customized informatics interface allows for the facile identification of antagonistic, additive and synergistic outcomes. Our approach facilitates the visualization of potency shifts, as well as efficacy enhancements for drugs in combination across a myriad of phenotypic assays. The standards of care for many diseases, including therapies for multiple types of cancer, involve drug combinations. Drug regimens can be comprised of as many as five or more agents such as R-CHOP (rituximab, cyclophosphamide, hydroxydaunomycin doxorubicin, oncovin vincristine, and prednisone) which is commonly used for the treatment of non-Hodgkins lymphomas. Many of these therapies are the result of long and painstaking clinical trial-and-error. The identification of clinically useful combination therapies in this way is untenable and methods to discover translatable drug combinations in pre-clinical settings are urgently needed. NCATS researchers have, therefore, established a high-throughput platform for analyzing drugs in combination. The outcomes of these studies include both basic research discoveries (novel interactions between diverse signaling pathways) and translational (discovery of new drug combinations for clinical evaluation). Highlighted projects include: -Identification of drugs that amplify the actions of ibrutinib in B-cell driven cancers; -Evaluation of the combinatorial drug landscape for malaria; -Identification of drugs that combine with Jak inhibitors in human IL-2 dependent adult T-cell leukemia; -Immunotoxin-based drug combinations for the treatment of epithelial and hematologic cancers; -Drug combinations for combating Ebola.

NCAT的基质筛选旨在使用定量的高通量组合筛选平台来鉴定多种疾病的协同药物组合。定制的信息学接口可以轻松识别拮抗，加性和协同结果。我们的方法促进了效力转移的可视化，以及在多种表型测定中结合使用药物的功效。许多疾病的护理标准，包括多种癌症的疗法，涉及药物组合。药物方案可以由多达五种或更多的药物组成，例如R-Chop（利妥昔单抗，环磷酰胺，羟基二莫霉素多氧霉素，Oncovin长春蛋白和泼尼松），这些药物通常用于治疗非霍多高素淋巴瘤。这些疗法中的许多是漫长而艰苦的临床反复试验的结果。以这种方式鉴定临床上有用的组合疗法是站不住脚的，并且迫切需要在临床前环境中发现可翻译药物组合的方法。因此，NCAT的研究人员建立了一个高通量平台，用于分析组合药物。这些研究的结果包括基础研究发现（不同的信号通路之间的新型相互作用）和翻译（发现新药组合以进行临床评估）。突出显示的项目包括： - 鉴定在B细胞驱动的癌症中放大伊布鲁替尼的作用的药物； - 对疟疾的组合药物景观进行评估； - 鉴定与人IL-2成人T细胞白血病中JAK抑制剂结合的药物； - 基于免疫毒素的药物组合，用于治疗上皮和血液学癌； - 用于对抗埃博拉病毒的药物组合。