药物基因组学与个体化用药与床与创新药物开发长沙ppt7.84MB.ppt

* * Childhood ALL 3 non-synonymous SNPs account for over 90% of the clinically relevant TPMT mutations and result in a trimodal distribution of TPMT activity * One of the best examples of diagnosing disease more effectively involves the most common form of childhood leukemia—acute lymphoblastic leukemia. Genetic tests are able to determine the exact chromosomal structure of the individual child’s disease. That allows physicians to select the optimal drug and dosage for each child. You can see some of the results: In 1962, about 4 percent of children were cured. Now that is over 80 percent. * * * * * * * * * * * Prescribed for serious indications * * * * * * * * ****Optional for a more advanced class or for people with more time**** * Slide 16a： * * * * * * Doctors hope that by studying SNP profiles in populations, correlations will emerge between certain SNP profiles and specific responses to cancer treatment. In the earlier example of two breast cancer patients, one did respond to the specific drug treatment, and the other did not. It may soon be possible to show that an entire group of patients responding well to breast cancer treatment repeatedly displays profiles within a recurring set (e.g., A and E), while a group of nonresponders repeatedly displays profiles outside the set. In the future, after a doctor has diagnosed breast cancer in a new patient, he or she may also request a SNP profile and use the information to help advise his patient about her treatment options. 病人或动物模型功能基因组学 全長cDNA文库、基因表达谱 蛋白质组及序列、蛋白质间相互作用 应用PGx发现新靶标和开发新药之六步 敲除/转基因小鼠功能基因组学、基因表达谱 蛋白质组学、表达谱 与蛋白質序列 抗体、RNAi 等抑制剂 建立化合物/天然物文库供高通量分析 组合化学 重组蛋白之細胞表現系統。 药物设计、制剂 PK/PD, DNA芯片动物細胞水平药理学评价 生物信息学：药物模拟、虚拟筛选 药效、药理、药代、安全性评价 表达谱分析、蛋白质相互作用 患者基因檢查与分层 有效/无效者SNP谱 表达谱分析比较 发现疾病基因及靶点 鉴定疾病基因及靶点 化合物高通量筛选 先导化合物优化 临床前试验 临床试验 1st step：探討疾病基因及其靶分子： (a) 所用材料：(1) 患病者及疾病模型动物；(2) 功能基因组学；(3) 全長cDNA文库；(4) 基因表达谱；(5) 蛋白质组分析。 (b) 生物信息学：(1) 表达谱 (如芯片)分析；(2) 蛋白質序列分析；(3) 蛋白质與蛋白质相互作用之预测。 2nd step：鉴定疾病基因 (a) 蛋白质组学：(1)