Mitochondrial Target for Radiation Mitigation
Mitochondrial Target for Radiation Mitigation
批准号:
8515290
负责人:
JOEL S GREENBERGER
金额:
$271.52万
依托单位国家:
美国
项目类别:
财政年份:
2005
资助国家:
美国
项目状态:
已结题
起止时间:
2005-09-30 至 2015-08-31
关键词:
ApoptosisApoptoticBiological MarkersBiometryCardiolipinsCaspaseCell DeathCell Membrane PermeabilityCellsCytochromesCytoplasmDNA strand breakDrug Delivery SystemsEventExtravasationLeadManganese Superoxide DismutaseMitochondriaMolecularNitric Oxide SynthaseNuclearOrganOxidative StressPathway interactionsPharmaceutical ChemistryPharmaceutical PreparationsPilot ProjectsRadiationSmall Interfering RNAStabilizing AgentsStandardizationTerrorismTissuesinhibitor/antagonistinnovationirradiationmitochondrial membranenitrationnovelpreventprogramsresponsesmall moleculestress activated protein kinase
中文摘要
描述(由申请方提供):电离辐射诱导的细胞、组织和器官损伤涉及核DNA链断裂以及相关的活化,并通过细胞质将应激活化蛋白激酶和其他启动细胞凋亡的分子转运至线粒体。线粒体的氧化应激事件激活分子级联反应,导致线粒体膜渗透性、细胞色素C泄漏和激活细胞死亡的半胱天冬酶途径。我们建议开发辐射缓解药物,重点是中和线粒体对辐射损伤的早期反应中的特定步骤,这将防止不可逆的细胞死亡。项目1的重点是开发线粒体靶向的氮氧化物、一氧化氮合酶抑制剂和p53/mdm 2/mdm 4抑制剂。项目2开发了靶向心磷脂/细胞色素C相互作用的小分子,以稳定线粒体功能。项目3使用siRNA靶向鉴定辐射诱导的RNA,以鉴定新型辐射缓解药物。项目4旨在确定通过防止硝化来稳定线粒体锰超氧化物歧化酶的试剂。项目5旨在开发小分子的p53抑制剂,从而稳定p53的抗凋亡作用。八个核心(A)行政,B)试点项目,C)生物标志物,D)创新药物化学,E)智能药物递送,F)生物统计学,G)放射生物学标准化和H)化学信息学支持五(5)个项目。
英文摘要
DESCRIPTION (provided by applicant): Ionizing irradiation-induced damage to cells, tissues, and organs involves nuclear DNA strand breaks and associated activation and transport through the cytoplasm to the mitochondria of stress activated protein kinases and other molecules which initiate apoptosis. Oxidative stress events at the mitochondria activate a molecular cascade leading to mitochondrial membrane permeability, cytochrome C leakage, and activation ofthe caspase pathway for cell death. We propose to develop radiation mitigator drugs by focus on neutralizing mitochondrial specific steps in early response to irradiation damage which will prevent irreversible cell death. Project 1 focuses on developing mitochondrial targeted nitroxides, nitric oxide synthase inhibitors and p53/mdm2/mdm4 inhibitors. Project 2 develops small molecules to target cardiolipin/cytochrome C interaction to stabilize mitochondrial function. Project 3 uses siRNA targeting to identify RNAs induced by radiation to identify novel radiation mitigator drugs. Project 4 seeks to identify agents that stabilize mitochondrial manganese superoxide dismutase by preventing nitration. Project 5 seeks to develop small molecule inhibitors of PUMA thereby stabilizing the anti apoptotic effects of p53. Eight cores (A) administrative, B) pilot project, C) biomarkers, D) innovative medicinal chemistry, E) smart drug delivery, F) biostatistics, G) radiobiological standardization and H) chemoinformatics support the five (5) projects.
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会议论文
LR-IL-22 for Mitigation and Management of Radiation Injuries
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批准号:10569299
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项目类别:
-
资助金额:$56.02万
-
财政年份:2022
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负责人:JOEL S GREENBERGER
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依托单位:
Mitigation of Ionizing Irradiation-Induced Intestinal Damage by Second-Generation Probiotics LR-IL-22 and LR-IFN-β
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批准号:10380676
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项目类别:
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资助金额:$30.0万
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财政年份:2021
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负责人:JOEL S GREENBERGER
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依托单位:
Mitochondrial Targeted Small Molecule Radiation Mitigators
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批准号:8010782
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项目类别:
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资助金额:$25.01万
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财政年份:2010
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负责人:JOEL S GREENBERGER
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依托单位:
Pilot Project's Core
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批准号:8010803
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项目类别:
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资助金额:$41.46万
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财政年份:2010
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负责人:JOEL S GREENBERGER
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依托单位:
Administrative Core
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批准号:8010802
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项目类别:
-
资助金额:$12.46万
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财政年份:2010
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负责人:JOEL S GREENBERGER
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依托单位:
Mitochondrial Targeting Against Radiation Damage
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批准号:7922793
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项目类别:
-
资助金额:$30.0万
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财政年份:2009
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负责人:JOEL S GREENBERGER
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依托单位:
Mechanism of Irradiation Pulmonary Fibrosis
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批准号:8082771
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项目类别:
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资助金额:$28.27万
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财政年份:2008
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负责人:JOEL S GREENBERGER
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依托单位:
Mechanism of Irradiation Pulmonary Fibrosis
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批准号:7645724
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项目类别:
-
资助金额:$29.14万
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财政年份:2008
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负责人:JOEL S GREENBERGER
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依托单位:
Mechanism of Irradiation Pulmonary Fibrosis
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批准号:7364772
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项目类别:
-
资助金额:$29.14万
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财政年份:2008
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负责人:JOEL S GREENBERGER
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依托单位:
Mechanism of Irradiation Pulmonary Fibrosis
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批准号:8270375
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项目类别:
-
资助金额:$28.27万
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财政年份:2008
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负责人:JOEL S GREENBERGER
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依托单位:
Mechanism of Irradiation Pulmonary Fibrosis
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批准号:7849691
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项目类别:
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资助金额:$29.14万
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财政年份:2008
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负责人:JOEL S GREENBERGER
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依托单位:
CAREER DEVELOPMENT PROGRAM
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批准号:7088511
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项目类别:
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资助金额:$7.0万
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财政年份:2006
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负责人:JOEL S GREENBERGER
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依托单位:
Mitochondrial Target for Radiation Mitigation
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批准号:8718982
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项目类别:
-
资助金额:$282.72万
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财政年份:2005
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负责人:JOEL S GREENBERGER
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依托单位:
Mitochondrial Targeting Against Radiation Damage
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批准号:7479163
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项目类别:
-
资助金额:$202.46万
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财政年份:2005
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负责人:JOEL S GREENBERGER
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依托单位:
Mitochondrial Targeting Against Radiation Damage
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批准号:7126387
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项目类别:
-
资助金额:$201.16万
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财政年份:2005
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负责人:JOEL S GREENBERGER
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依托单位:
Administrative Core
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批准号:8940565
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项目类别:
-
资助金额:$9.74万
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财政年份:2005
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负责人:JOEL S GREENBERGER
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依托单位:
Signature-Directed Combination Mitigator Therapy Based on GS-Nitroxides
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批准号:9127903
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项目类别:
-
资助金额:$44.98万
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财政年份:2005
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负责人:JOEL S GREENBERGER
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依托单位:
Mitochondrial Targeting Against Radiation Damage
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批准号:7029375
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项目类别:
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资助金额:$200.0万
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财政年份:2005
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负责人:JOEL S GREENBERGER
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依托单位:
Training and Education
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批准号:7055215
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项目类别:
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资助金额:$12.76万
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财政年份:2005
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负责人:JOEL S GREENBERGER
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依托单位:
MnSOD-PL Irradiation Protection of the Oral Cavity
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批准号:6874571
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项目类别:
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资助金额:$23.92万
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财政年份:2005
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负责人:JOEL S GREENBERGER
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依托单位:
海外基金