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. Simmons癌症中心 化学和癌症科学计划 项目摘要/摘要 化学与癌症（CC）计划结合了合成和医学化学家的专业知识， 分子生物学家，生物化学家，结构生物学家和临床科学家发现，设计和优化 在癌症中调节生物学途径的药物样小分子。共有16个 来自校园四个部门的成员。 CC的发现过程进行了两步 方法，从化学到生物学或生物学对化学方向开始。用于化学对生物学 方法，发现过程始于识别有选择性的自然或不自然的小分子 细胞毒性对人类癌细胞系，然后是严格的靶标识别程序。在这个“发现”期间 生物学”阶段，化学家设计特定的衍生物，以帮助生化下拉和交联研究。 或者，如果特定的耐药克隆针对较小的感兴趣分子，则可以产生遗传和 分子生物学研究可以提供其他方法来识别目标途径和/或药物 电阻机制。这种公正的方法有望确定新型癌症特异性途径 可以对概念证明，早期药物发现的努力进行化学询问/调节。在生物学到 化学方法，关于特定生物学的“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科学计划将继续以以下主题进行广泛的继续： ·主题1。识别癌细胞特异性小分子毒素的分子靶标； ·主题2。新颖的癌细胞特异性途径的生化清扫； ·主题3。概念概念临床前开发癌细胞特异性小分子毒素；和 ·主题4。缺氧反应途径的解剖，调节和靶向。 CC计划当前对同行评审的资金从NCI中得到150万美元和280万美元 来自德克萨斯州癌症预防和研究所的总审查资金为710万美元。 CC 自2009年以来，计划成员已经撰写了103份同行评审的出版物，其中有19％是内部的 程序化和30％的程序间截面，其中15％与其他调查员跨机构化 NCI指定的癌症中心。