Nucleophilic Inhibitors for Targeting Redox-Sensitive Kinases
用于靶向氧化还原敏感激酶的亲核抑制剂
基本信息
- 批准号:8631369
- 负责人:
- 金额:$ 39.22万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-12-01 至 2017-11-30
- 项目状态:已结题
- 来源:
- 关键词:6H,8H-3,4-dihydropyrimido(4,5-c)(1,2)oxazin-7-oneAchievementActive SitesAdvanced Malignant NeoplasmAmino AcidsAntineoplastic AgentsBinding SitesBiochemicalBiochemistryBiological AssayBiological ModelsCancer cell lineCase StudyCellular AssayChemicalsChemistryClinical TrialsCysteineDevelopmentDiseaseDrug KineticsDrug TargetingEffectivenessElectronsEnvironmentEpidermal Growth Factor ReceptorEvaluationExposure toFoundationsFutureGefitinibGlutathioneGoalsHumanHuman DevelopmentHydrogen PeroxideIn VitroInterventionInvestigationLeadLibrariesLightLysineMalignant NeoplasmsModelingModificationMolecularOxidation-ReductionOxidative StressPharmaceutical PreparationsPhase I Clinical TrialsPhosphotransferasesPhysiologicalPlayProtein KinaseProtein Tyrosine KinaseProteinsRegulationResistanceRoleSignal PathwaySite-Directed MutagenesisStructureSulfenic AcidsSulfurTestingTherapeutic Human ExperimentationTissue SampleToxic effectTreatment EfficacyTumor TissueWorkadductanti-cancer therapeuticbasecancer celldesignimprovedin vivoinhibitor/antagonistinsightkinase inhibitorlapatinibnovelnovel diagnosticsnovel strategiesoxidationpre-clinicalpreventprototypepublic health relevancereceptorscaffoldsmall moleculestandard of caretooltumor progressiontumor xenograft
项目摘要
Abstract
Kinase inhibition has emerged as the preeminent point of intervention for developing novel anti-cancer
therapeutics and research tool compounds to dissect signaling pathways. In this proposal, we focus on redox-
sensitive kinases and the development of inhibitors that target the oxidized form of these proteins, which are
prevalent in many human cancers. In Aim 1, we identify chemical warheads that target cysteine oxidation
species. In Aim 2, we develop molecules that target oxidized tyrosine kinases and evaluate their effectiveness
in vitro and cancer cell-based assays. In Aim 3, we evaluate the therapeutic efficacy of new kinase inhibitors.
Inhibitors identified in this study will serve as vital tools for dissecting mechanistic details of kinase redox
regulation and the relationship between oxidative stress/aberrant kinase activity in cancer. Furthermore, these
collective aims will create a foundation for the development of an entirely new class of anti-cancer drugs.
抽象的
激酶抑制已成为开发新型抗癌药物的重要干预点
用于剖析信号通路的治疗和研究工具化合物。在本提案中,我们重点关注氧化还原
敏感激酶和针对这些蛋白质氧化形式的抑制剂的开发,这些蛋白质是
普遍存在于许多人类癌症中。在目标 1 中,我们确定了针对半胱氨酸氧化的化学弹头
物种。在目标 2 中,我们开发了针对氧化酪氨酸激酶的分子并评估其有效性
体外和基于癌细胞的测定。在目标 3 中,我们评估了新激酶抑制剂的治疗效果。
本研究中确定的抑制剂将作为剖析激酶氧化还原机制细节的重要工具
癌症中氧化应激/异常激酶活性的调节和关系。此外,这些
集体目标将为开发全新一类抗癌药物奠定基础。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Kate Suzanne Carroll其他文献
Kate Suzanne Carroll的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Kate Suzanne Carroll', 18)}}的其他基金
Redox Modification and Targeting of Mutant KRas in Cancer
癌症中突变 KRa 的氧化还原修饰和靶向
- 批准号:
10595875 - 财政年份:2018
- 资助金额:
$ 39.22万 - 项目类别:
Redox Modification and Targeting of Mutant KRas in Cancer
癌症中突变 KRa 的氧化还原修饰和靶向
- 批准号:
10162539 - 财政年份:2018
- 资助金额:
$ 39.22万 - 项目类别:
Redox Modification and Targeting of Mutant KRas in Cancer
癌症中突变 KRa 的氧化还原修饰和靶向
- 批准号:
9912729 - 财政年份:2018
- 资助金额:
$ 39.22万 - 项目类别:
Nucleophilic Inhibitors for Targeting Redox-Sensitive Kinases
用于靶向氧化还原敏感激酶的亲核抑制剂
- 批准号:
9187426 - 财政年份:2013
- 资助金额:
$ 39.22万 - 项目类别:
Nucleophilic Inhibitors for Targeting Redox-Sensitive Kinases
用于靶向氧化还原敏感激酶的亲核抑制剂
- 批准号:
8969670 - 财政年份:2013
- 资助金额:
$ 39.22万 - 项目类别:
Nucleophilic Inhibitors for Targeting Redox-Sensitive Kinases
用于靶向氧化还原敏感激酶的亲核抑制剂
- 批准号:
8776280 - 财政年份:2013
- 资助金额:
$ 39.22万 - 项目类别:
Probing the role of cysteine sulfenylation in cell signaling
探讨半胱氨酸磺酰化在细胞信号传导中的作用
- 批准号:
8342423 - 财政年份:2012
- 资助金额:
$ 39.22万 - 项目类别:
Probing the role of cysteine sulfenylation in cell signaling
探讨半胱氨酸磺酰化在细胞信号传导中的作用
- 批准号:
8653970 - 财政年份:2012
- 资助金额:
$ 39.22万 - 项目类别:
Chemical Tools for Probing Cysteine Sulfenation and Sulfination Redox Biology
用于探测半胱氨酸磺化和磺化氧化还原生物学的化学工具
- 批准号:
10658440 - 财政年份:2012
- 资助金额:
$ 39.22万 - 项目类别:
Probing the role of cysteine sulfenylation in cell signaling
探讨半胱氨酸磺酰化在细胞信号传导中的作用
- 批准号:
9380891 - 财政年份:2012
- 资助金额:
$ 39.22万 - 项目类别:
相似海外基金
Collaborative Research: Using Adaptive Lessons to Enhance Motivation, Cognitive Engagement, And Achievement Through Equitable Classroom Preparation
协作研究:通过公平的课堂准备,利用适应性课程来增强动机、认知参与和成就
- 批准号:
2335802 - 财政年份:2024
- 资助金额:
$ 39.22万 - 项目类别:
Standard Grant
Collaborative Research: Using Adaptive Lessons to Enhance Motivation, Cognitive Engagement, And Achievement Through Equitable Classroom Preparation
协作研究:通过公平的课堂准备,利用适应性课程来增强动机、认知参与和成就
- 批准号:
2335801 - 财政年份:2024
- 资助金额:
$ 39.22万 - 项目类别:
Standard Grant
A Longitudinal Study of the Relationship between Participation in a Comprehensive Exercise Program and Academic Achievement
参加综合锻炼计划与学业成绩之间关系的纵向研究
- 批准号:
24K14615 - 财政年份:2024
- 资助金额:
$ 39.22万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Collaborative Research: Characterizing Best Practices of Instructors who Have Narrowed Performance Gaps in Undergraduate Student Achievement in Introductory STEM Courses
合作研究:缩小本科生 STEM 入门课程成绩差距的讲师的最佳实践
- 批准号:
2420369 - 财政年份:2024
- 资助金额:
$ 39.22万 - 项目类别:
Standard Grant
Collaborative Research: Using Adaptive Lessons to Enhance Motivation, Cognitive Engagement, And Achievement Through Equitable Classroom Preparation
协作研究:通过公平的课堂准备,利用适应性课程来增强动机、认知参与和成就
- 批准号:
2335800 - 财政年份:2024
- 资助金额:
$ 39.22万 - 项目类别:
Standard Grant
WTG: Diffusion of Research on Supporting Mathematics Achievement for Youth with Disabilities through Twitter Translational Visual Abstracts
WTG:通过 Twitter 翻译视觉摘要传播支持残疾青少年数学成就的研究
- 批准号:
2244734 - 财政年份:2023
- 资助金额:
$ 39.22万 - 项目类别:
Standard Grant
The Impact of Emotional Experiences of Pride on Long-Term Goal Achievement Behaviors in Elite Athletes
骄傲的情感体验对优秀运动员长期目标实现行为的影响
- 批准号:
23K16740 - 财政年份:2023
- 资助金额:
$ 39.22万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Meta-Analysis of the Instructional-Relational Model of Student Engagement and Math Achievement: A Moderation and Mediation Approach
学生参与度和数学成绩的教学关系模型的元分析:一种调节和中介方法
- 批准号:
2300738 - 财政年份:2023
- 资助金额:
$ 39.22万 - 项目类别:
Standard Grant
Improving maths achievement in children with speech, language, and communication needs through 'collaborative vocabulary teaching'
通过“协作词汇教学”提高有言语、语言和交流需求的儿童的数学成绩
- 批准号:
2890475 - 财政年份:2023
- 资助金额:
$ 39.22万 - 项目类别:
Studentship
HSI Institutional Transformation Project: Retention and Achievement for Introductory STEM English Learners (RAISE)
HSI 机构转型项目:STEM 英语入门学习者的保留和成就 (RAISE)
- 批准号:
2225178 - 财政年份:2023
- 资助金额:
$ 39.22万 - 项目类别:
Continuing Grant