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

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
项目类别：
财政年份：
--
资助国家：
美国
项目状态：
未结题
起止时间：
至
来源：
https://reporter.nih.gov/project-details/10689610
关键词：
Antineoplastic AgentsAutophagocytosisBiochemicalBiological AssayCell physiologyCellsCollaborationsDana-Farber Cancer InstituteDiseaseDisease modelDrug DesignEnzymesFundingGrowthLipidsMalignant NeoplasmsNational Center for Advancing Translational SciencesPhosphatidylinositolsPhosphotransferasesPlayRoleSeriesSignal TransductionStructureTP53 geneWorkadvanced diseasebasebiological adaptation to stresscancer cellinhibitorinsulin signalingkinase inhibitormedical schoolsmutantnovelpharmacokinetics and pharmacodynamicspre-clinicalsmall molecule inhibitor

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相关文献

中文摘要
翻译
这个先前的合作团队-由威尔康奈尔医学院，哈佛医学院和达纳法伯癌症研究所和NCATS的小组组成-已经发现了脂质激酶PI 5 P4 Ka/的新型抑制剂作为潜在的抗癌药物适应症。在针对PI 5 P4 Ka和B的广泛SAR活动之后，Sanford Burnham的布鲁克Emerling表明，在自噬上调的条件下，关键的双重PI 5 P4 Ka/B抑制剂可以杀死p53突变癌细胞。这导致了CBC资助的SAR活动，该活动涉及相同系列和其他可能的系列，这些系列使用基于结构的药物设计与SBP合作开发生物可利用的PI 5 P4 K α和β双重抑制剂。
英文摘要
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.
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