Targeting Causal Cancer Genes with Small Molecules

用小分子靶向致癌基因

基本信息

批准号：
7852284
负责人：
STUART L SCHREIBER
金额：
$ 224.85万
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 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7852284
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 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.