Chemistry and Cancer Scientific Program

化学和癌症科学计划

• 批准号: 10260734
• 负责人: JEF KAREL DE BRABANDER
• 金额: $ 3.22万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-03 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10260734
• 关键词: Agonist; Biochemical; Biological; Biology; Cancer Center; Cancer Center Support Grant; Cancer cell line; Chemicals; Chemistry; Dissection; Drug resistance; Funding; Genetic; Human; Hypoxia; Malignant Neoplasms; Medical center; Molecular; Molecular Target; NCI-Designated Cancer Center; Pathway interactions; Peer Review; Pharmaceutical Preparations; Phase; Process; Publications; Regulation; Research Institute; Research Personnel; Scientist; Structural Biologist; Testing; Texas; Toxin; cancer cell; cancer prevention; crosslink; cytotoxic; design; drug discovery; inter-institutional; interest; member; novel; preclinical development; programs; resistance mechanism; response; small molecule

Harold C. Simmons Cancer Center Chemistry and Cancer Scientific Program Project Summary/Abstract The Chemistry and Cancer (CC) Program combines the expertise of synthetic and medicinal chemists, molecular biologists, biochemists, structural biologists, and clinician scientists to discover, design, and optimize drug-like small molecules that regulate biological pathways deregulated in cancer. There are a total of 16 members who are drawn from 4 departments on campus. CC's discovery process takes a two-pronged approach, starting from a chemistry-to-biology or a biology-to-chemistry direction. For the chemistry-to-biology approach, the discovery process starts with identifying natural or unnatural small molecules that are selectively cytotoxic to human cancer cell lines, followed by a rigorous target identification program. During this “discovery biology” phase, chemists design specific derivatives to aid in biochemical pull-down and cross-linking studies. Or, if specific drug-resistant clones against the small molecule of interest can be generated, genetic and molecular biological studies can provide additional approaches to identify target pathways and/or drug resistance mechanisms. This unbiased approach is expected to identify novel cancer-specific pathways that can be chemically interrogated/regulated for proof-of-concept, early drug-discovery efforts. In the biology-to- chemistry approach, hypotheses regarding the “drugability” and cancer relevance of specific biological pathways investigated by Simmons Cancer Center scientists can be tested with small-molecule agonists or antagonists. The CC Scientific Program will continue broadly with the following themes: · Theme 1. Identifying the molecular targets of cancer cell–specific small-molecule toxins; · Theme 2. Biochemical dissection of novel, cancer cell–specific pathways; · Theme 3. Proof-of-concept preclinical development of cancer cell–specific small-molecule toxins; and · Theme 4. Dissection, regulation, and targeting of the hypoxia response pathway. Current peer-reviewed funding for the CC Program is highlighted by $1.5 million from the NCI and $2.8 million from Cancer Prevention and Research Institute of Texas for total peer-reviewed funding of $7.1 million. CC Program members have authored 103 peer-reviewed publications since 2009, of which 19% were intra- programmatic and 30% inter-programmatic, and 15% of them inter-institutional with investigators from other NCI-designated cancer centers.

Harold C.西蒙斯癌症中心 化学与癌症科学计划 项目总结/摘要 化学与癌症（CC）计划结合了合成和药物化学家的专业知识， 分子生物学家，生物化学家，结构生物学家和临床科学家，以发现，设计和优化 在癌症中调节生物途径的类药物小分子被解除管制。一共有16 成员来自校园内的4个部门。CC的发现过程需要双管齐下 方法，从化学到生物学或生物学到化学方向开始。从化学到生物学 方法，发现过程开始于识别选择性地结合在一起的天然或非天然小分子。 对人癌细胞系具有细胞毒性，随后进行严格的靶标鉴定程序。在这次“发现”中， 在“生物学”阶段，化学家设计特定的衍生物，以帮助生物化学下拉和交联研究。 或者，如果可以产生针对感兴趣的小分子的特异性耐药克隆，则遗传和 分子生物学研究可以提供另外的方法来鉴定靶途径和/或药物 抵抗机制这种无偏见的方法有望识别新的癌症特异性途径， 可以通过化学方法进行查询/调节，用于概念验证，早期药物发现工作。在生物学上， 化学方法，关于特定生物制剂的“可药性”和癌症相关性的假设 西蒙斯癌症中心科学家研究的途径可以用小分子激动剂或 对手。 CC科学计划将继续广泛地围绕以下主题： ·主题1。识别癌细胞特异性小分子毒素的分子靶点; ·主题2。新的癌细胞特异性通路的生物化学剖析; ·主题3。癌细胞特异性小分子毒素的概念验证临床前开发;以及 ·主题4。缺氧反应通路的解剖、调节和靶向。 目前，CC计划的同行评审资金由NCI的150万美元和280万美元突出显示。 来自德克萨斯州癌症预防和研究所，共获得710万美元的同行评审资金。CC 自2009年以来，项目成员撰写了103篇同行评审的出版物，其中19%是内部出版物。 方案和30%方案间，其中15%与其他机构的调查员进行机构间调查。 NCI指定的癌症中心。