In Silico Screening for Cancer Targets

癌症靶标的计算机筛查

• 批准号: 7592817
• 负责人: MARC NICKLAUS
• 金额: $ 43.5万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7592817
• 关键词: ABCG2 gene; Annual Reports; Biological Assay; Biophysics; CCR; Cancer Biology; Cells; Clinical; Collaborations; Computer Simulation; Computer software; DNA; Databases; Development; Genetic; Goals; Heat-Shock Proteins 90; In Vitro; Intercalating Agents; Laboratories; Lead; Malignant Neoplasms; Metabolism; Molecular; Molecular Target; Numbers; PH Domain; Pharmaceutical Chemistry; Pharmacology; Polo-Box Domain; Principal Investigator; Program Development; Proteins; Resources; Sampling; Screening for cancer; Screening procedure; Therapeutic; Tumor Promotion; Urologic Oncology; Work; analog; base; carcinogenesis; design; human PLK1 protein; inhibitor/antagonist; interest; lecithin-retinol acyltransferase; novel; novel therapeutics; small molecule; src Homology Region 2 Domain; tyrosyl-DNA phosphodiesterase

In collaboration with several Principal Investigators at the CCR/NCI, <em>in silico</em> screening of large small-molecule databases are being conducted for a number of molecular targets relevant for cancer. We are using the <A HREF="http://ccr.cancer.gov/staff/staff.asp?profileid=6282">CADD Group's</a> resources, including our screening <A HREF="http://ccrintra.cancer.gov/cms/annual_reports/projects/printer_friendly_report.asp?ProjID=6190">databases</a> to generate lists of compounds to be purchased from <A HREF= "http://www.chemnavigator.com/nih.asp">commercial suppliers</a>, with the goal of obtaining novel lead compounds in <em>in vitro</em> and/or cell-based assays. <BR> Currently, we are predominantly working on the targets Akt (PH domain), in collaboration with Phillip Dennis, Cancer Therapeutics Branch, CCR, NCI; c-Met, in collaboration with Donald Bottaro, Urologic Oncology Branch, CCR, NCI, and Terrence R. Burke, Jr., Laboratory of Medicinal Chemistry, CCR, NCI; HSP90, in collaboration with Len Neckers, Cell & Cancer Biology Branch, CCR, NCI; polo-Box domain of polo-like kinase 1, in collaboration with Kyung S. Lee, Laboratory of Metabolism, CCR, NCI; Grb2 SH2 domain, in collaboration with Terrence R. Burke, Jr., Laboratory of Medicinal Chemistry, CCR, NCI; PKC, in collaboration with Peter Blumberg, Laboratory of Cancer Biology and Genetics, CCR, NCI, and Victor E. Marquez, Laboratory of Medicinal Chemistry, CCR, NCI; tyrosyl-DNA phosphodiesterase (Tdp1), in collaboration with Yves Pommier, Laboratory of Molecular Pharmacology, CCR, NCI; and imidazoacridone DNA intercalators, in collaboration with Sergei Tarasov, Structural Biophysics Laboratory, CCR, NCI. <BR> Targets for which work has been completed include lecithin retinol acyltransferase (LRAT) and related proteins, in collaboration with Denise Simmons and Luigi DeLuca, formerly Laboratory of Cellular Carcinogenesis and Tumor Promotion, CCR, NCI; and ABCG2, in collaboration with Heidi Bokesch, Molecular Targets Development Program, CCR, NCI. <BR> For Akt, c-Met, and the polo-Box domain of plk1, initial hit sets have been generated, screening samples purchased, and these samples assayed by our collaborators. First results show inhibitory activity for a number of samples in each one of these assay.

与CCR/NCI的几名首席研究人员合作，<em>在Silico</em>中，正在对一些与癌症有关的分子靶标进行大型小分子数据库的筛选。我们正在使用<a href=“http://ccr.cancer.gov/staff/staff.asp?profileid=6282”>CADD集团的</a>资源，包括我们的筛选<a href=“http://ccrintra.cancer.gov/cms/annual_reports/projects/printer_friendly_report.asp?ProjID=6190”>databases</a>来生成从<a href=“http://www.chemnavigator.com/nih.asp”>commercial供应商</a>购买的化合物列表，目标是在<em>体外</em>和/或基于细胞的分析中获得新的先导化合物。<br>目前，我们主要与NCI CCR癌症治疗科Phillip Dennis合作研究靶标Akt(PH域)；与NCI CCR泌尿外科肿瘤科Donald Bottaro和NCI CCR药物化学实验室小特伦斯·R·伯克合作研究c-Met；与NCI CCR新陈代谢实验室Len Neckers合作研究HSP90；与NCI CCR新陈代谢实验室Lee Kyung S.Lee合作研究Polo-like kin1的Polo-Box结构域；GRB2 SH2领域，与小特伦斯·R·伯克合作，药物化学实验室，CCR，NCI；PKC，与Peter Blumberg，癌症生物学和遗传学实验室，CCR，NCI，和Victor E.Marquez，药物化学实验室，CCR，NCI；酪氨酰DNA磷酸二酯酶(Tdp1，与Yves Pommier，分子药理实验室，CCR，NCI合作)；以及咪唑并嘧啶酮DNA插入剂，与Sergei Tarasov，结构物理实验室，CCR，NCI合作。<br>已完成工作的靶标包括卵磷脂视黄醇酰基转移酶(LRAT)和相关蛋白质，与Denise Simmons和Luigi DeLuca合作，前细胞癌变和肿瘤促进实验室，CCR，NCI；以及ABCG2，与Heidi Bokesch，分子靶标开发计划，CCR，NCI合作。<br>对于Akt、c-Met和PLK1的Polo-Box结构域，已经生成了初始命中集，筛选了购买的样本，并由我们的合作者对这些样本进行了分析。首先，结果显示，在每一种检测方法中，都有一些样品具有抑制活性。