HTS enabled examination of drug combinations

NCATS的基质筛选旨在利用定量高通量组合筛选平台确定治疗多种疾病的协同药物组合。定制的信息学界面可以方便地识别拮抗、加性和协同结果。我们的方法促进了效力变化的可视化，以及药物在无数表型分析中组合的功效增强。许多疾病的护理标准，包括多种癌症的治疗，都涉及药物组合。药物方案可由多达五种或更多种药物组成，如R-CHOP（利妥昔单抗、环磷酰胺、羟霉素、长春新碱和强的松），通常用于治疗非霍奇金淋巴瘤。这些疗法中的许多都是长期艰苦的临床试验和错误的结果。以这种方式确定临床有用的联合疗法是站不住脚的，迫切需要在临床前环境中发现可翻译的药物组合。因此，NCATS的研究人员已经建立了一个高通量的平台来分析药物组合。这些研究的结果包括基础研究发现（不同信号通路之间的新相互作用）和转化（发现用于临床评估的新药物组合）。

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.