Identification of Inhibitors of the Lipid Kinase PI5P4Ka/B as Potential Anti-Cancer Agents

鉴定脂质激酶 PI5P4Ka/B 抑制剂作为潜在的抗癌药物

• 批准号: 10689610
• 负责人: Min Shen
• 金额: $ 42.54万
• 依托单位: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
• 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/10689610
• 关键词: Antineoplastic Agents; Autophagocytosis; Biochemical; Biological Assay; Cell physiology; Cells; Collaborations; Dana-Farber Cancer Institute; Disease; Disease model; Drug Design; Enzymes; Funding; Growth; Lipids; Malignant Neoplasms; National Center for Advancing Translational Sciences; Phosphatidylinositols; Phosphotransferases; Play; Role; Series; Signal Transduction; Structure; TP53 gene; Work; advanced disease; base; biological adaptation to stress; cancer cell; inhibitor; insulin signaling; kinase inhibitor; medical schools; mutant; novel; pharmacokinetics and pharmacodynamics; pre-clinical; small molecule inhibitor

This previous collaborative team - composed of groups from Weill Cornell Medical College, Harvard Medical School and the Dana Farber Cancer Institute and NCATS - had uncovered novel inhibitors of the lipid kinase PI5P4Ka/ as potential anti-cancer agents indications. After an extensive SAR campaign against PI5P4Ka and b, Brooke Emerling at Sanford Burnham showed that a key dual PI5P4Ka/b inhibitor can kill p53 mutant cancer cells under condition where autophagy is upregulated. This has led to a CBC funded SAR campaign on the same series and other possible series that use structure based drug design to develop bioavailable dual inhibitors of PI5P4K alpha and beta in collaboration with SBP.

这个先前的合作团队由来自威尔·康奈尔医学院、哈佛医学院、达纳·法伯癌症研究所和NCATS的团队组成，发现了脂蛋白激酶PI5P4Ka/的新型抑制剂作为潜在的抗癌药物适应症。在针对PI5P4Ka和b的广泛SAR运动之后，Sanford Burnham的Brooke Emerling表明，一个关键的双重PI5P4Ka/b抑制剂可以在自噬上调的条件下杀死p53突变的癌细胞。这导致了CBC资助的同一系列和其他可能系列的SAR活动，这些系列使用基于结构的药物设计与SBP合作开发PI5P4Kα和β的生物可用双重抑制剂。