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Targeting Causal Cancer Genes with Small Molecules

用小分子靶向致癌基因

基本信息

批准号：
8464829
负责人：
STUART L SCHREIBER
金额：
$ 64.88万
依托单位：
BROAD INSTITUTE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-29 至 2013-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8464829
关键词：
Advanced Malignant Neoplasm Animal Model Animals Antineoplastic Agents Area Binding Biochemical Biological Biological Assay Biology Cancer Biology Cancer Etiology Cells Chemicals Chemistry Collection Communication Communities Computer software Controlled Vocabulary Data Data Collection Dependency Development Disease Dose Electronics Ensure Evaluation Gene Expression Genome Genomics Health Human Image Analysis Informatics Institutes Investigation Laboratories Lead Malignant Neoplasms Management Information Systems Metadata Molecular Target National Cancer Institute Oncogenes Organism Pathway interactions Pharmaceutical Chemistry Pharmaceutical Preparations Plant Roots Production Protein Binding Proteins Proteomics PubChem RNA Interference Research Research Infrastructure Research Personnel Robotics Science Screening for cancer Screening procedure System Testing Therapeutic Therapeutic Intervention Translating Validation Work base cancer genomics cellular targeting clinically relevant design drug development drug discovery experience follow-up high throughput screening in vivo innovation insight novel novel therapeutics open source outreach pre-clinical pre-clinical research programs public health relevance research study response scale up small molecule success tool

项目摘要

DESCRIPTION (provided by applicant): Our understanding of how cancers begin, survive and progress is rapidly expanding through advances in cancer genomics and modern cancer biology. Although these insights suggest many new strategies for therapeutic intervention, they often require modulating targets against which the research community has had little experience or success developing small-molecule probes and drugs. Through the NCI Molecular Target Discovery and Development Center Network Pilot Program, we aim to overcome this challenge and to accelerate the discovery of novel therapeutics in cancer. The Broad-MTDDC will provide over 10 years of experience in both innovation and execution in small- molecule probe and drug development to the MTDDC Network to advance insights from the cancer biology community. We aim to innovate in fundamental chemistry so as to enable the discovery of small-molecule probes against even 'undruggable' cancer targets such as those emerging from genomic studies; to engage the cancer biology community and to bring small-molecule science to the root causes of cancer; and to solve the target I.D. problem, including by determining comprehensively the proteins to which small-molecule modulators of cancer pathways bind in or on cells. Furthermore, we will provide the cancer biology community with the robust infrastructure and expertise required to execute probe- and drug-development projects that aim to transform cancer therapeutics. Impact on human health. The Molecular Target Discovery and Development Center at the Broad Institute will discover small molecules that target the root causes and dependencies of cancer. These leads will serve as valuable starting points for new drug development programs. By providing early lead optimization and data from clinically relevant animal models, we aim to advance cancer drug discovery development. Furthermore, we will make all data associated with small-molecule probe development publicly available, enabling further discovery from the community and broader communication of our approaches to drug discovery. PUBLIC HEALTH RELEVANCE: The Molecular Target Discovery and Development Center at the Broad Institute will develop and execute small-molecule screens from the cancer biology community aimed at targeting the root causes and dependencies of cancer. We will focus on innovation in chemistry, screening, and preclinical research in order to access targets viewed as 'undruggable' using current tools and approaches. These projects will yield small- molecule probes that both enable pre-clinical validation of therapeutic strategies using animal models and serve as outstanding starting points for drug development.

描述（由申请人提供）：通过癌症基因组学和现代癌症生物学的进步，我们对癌症开始、存活和进展的理解正在迅速扩大。尽管这些见解提出了许多新的治疗干预策略，但它们通常需要调节靶点，而研究界在开发小分子探针和药物方面几乎没有经验或成功。通过NCI分子靶点发现和开发中心网络试点计划，我们的目标是克服这一挑战，并加速发现癌症的新疗法。 Broad-MTDDC将为MTDDC网络提供超过10年的小分子探针和药物开发创新和执行经验，以促进癌症生物学界的见解。我们的目标是在基础化学方面进行创新，以便能够发现小分子探针，即使是针对“不可治愈”的癌症靶点，例如从基因组研究中出现的靶点;参与癌症生物学社区，并将小分子科学带到癌症的根本原因;并解决目标ID。这是一个新的问题，包括通过全面确定癌症途径的小分子调节剂在细胞内或细胞上结合的蛋白质。此外，我们将为癌症生物学社区提供执行旨在改变癌症治疗的探针和药物开发项目所需的强大基础设施和专业知识。对人类健康的影响。布罗德研究所的分子靶点发现和开发中心将发现针对癌症根源和依赖性的小分子。这些线索将作为新药开发计划的宝贵起点。通过提供早期先导化合物优化和临床相关动物模型的数据，我们的目标是推进癌症药物的发现和开发。此外，我们将公开与小分子探针开发相关的所有数据，使社区能够进一步发现我们的药物发现方法并进行更广泛的交流。公共卫生相关性：布罗德研究所的分子靶点发现和开发中心将开发和执行来自癌症生物学社区的小分子筛选，旨在针对癌症的根本原因和依赖性。我们将专注于化学，筛选和临床前研究的创新，以便使用当前的工具和方法获得被视为“不可药用”的目标。这些项目将产生小分子探针，既可以使用动物模型对治疗策略进行临床前验证，又可以作为药物开发的优秀起点。