Therapeutic targeting of MYC interactions with an essential cofactor
MYC 与重要辅因子相互作用的治疗靶向
基本信息
- 批准号:10512309
- 负责人:
- 金额:$ 23万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-07-01 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAmino Acid MotifsBindingBiologicalBiological AssayBiomedical ResearchBreast Cancer CellCancer Cell GrowthCause of DeathCell ProliferationCellsCessation of lifeChimeric ProteinsChromatinCollaborationsComplexDNADevelopmentDown-RegulationEvolutionGene AmplificationGenesGenetic TranscriptionGoalsGrowthHelix-Turn-Helix MotifsHistone AcetylationHumanInstitutesLeadLeucine ZippersLuciferasesMYC Family ProteinMalignant NeoplasmsMass Spectrum AnalysisMeasurementMolecularMultienzyme ComplexesMutationNuclearNuclear ProteinOncogenicPharmaceutical PreparationsProtein InhibitionProteinsSeriesSignal PathwaySpecificityTRRAP geneTherapeuticTransactivationanti-cancer therapeuticanticancer activitybasecancer cellcancer therapycell growthcofactorexperimental studyhistone modificationin vivoinhibitormetaplastic cell transformationnanomolarnoveloncogene addictionoverexpressionpreclinical developmentprotein complexprotein functionrecruitresponsesmall molecule inhibitortargeted treatmenttheoriestherapeutic targettranscriptome sequencingtriple-negative invasive breast carcinoma
项目摘要
MYC is the most frequently amplified gene in human cancer and is overexpressed as a
consequence of mutations in diverse oncogenic signaling pathways in 70% of cancers. Given
the ubiquity of MYC as a driver of cancer, there is a critical unmet need to develop specific
drugs that inhibit MYC function as anti-cancer therapeutics. TRansactivation/tRansformation-
domain Associated Protein (TRRAP) is an essential nuclear cofactor for MYC, and small
molecule inhibitors of the MYC:TRRAP interaction are predicted to have potent anti-cancer
activity. We developed a luciferase-based assay to identify small molecule inhibitors of
MYC:TRRAP and initiated a collaboration with the Novartis Institute for Biomedical Research to
search their non-proprietary 50,000 drug-like compound set. We identified 33 diverse
compounds that show inhibitory activity for MYC:TRRAP in the nanomolar to micromolar
concentration range using our luciferase assay. We propose to use cellular and molecular
assays to determine which of these compounds inhibit native MYC:TRRAP complexes and
ascertain their specificity regarding other MYC and/or TRRAP interacting proteins. Promising
compounds will also be assayed for growth inhibitory activity in triple negative breast cancer
cells, which have high levels of MYC and determine if growth inhibition can be attributed to loss
of MYC function. A long-term goal is the preclinical development of our top lead compounds for
in vivo experimentation.
MYC是人类癌症中最常扩增的基因,并且作为一种基因过度表达
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
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MICHAEL David COLE其他文献
MICHAEL David COLE的其他文献
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{{ truncateString('MICHAEL David COLE', 18)}}的其他基金
Therapeutic targeting of MYC interactions with an essential cofactor
MYC 与重要辅因子相互作用的治疗靶向
- 批准号:
10655655 - 财政年份:2022
- 资助金额:
$ 23万 - 项目类别:
MYC Dependent Pathways in Apoptosis and Lymphomagenesis
细胞凋亡和淋巴瘤发生中的 MYC 依赖性途径
- 批准号:
7171755 - 财政年份:1999
- 资助金额:
$ 23万 - 项目类别:
MYC Dependent Pathways in Apoptosis and Lymphomagenesis
细胞凋亡和淋巴瘤发生中的 MYC 依赖性途径
- 批准号:
7341057 - 财政年份:1999
- 资助金额:
$ 23万 - 项目类别:
MYC Dependent Pathways in Apoptosis and Lymphomagenesis
细胞凋亡和淋巴瘤发生中的 MYC 依赖性途径
- 批准号:
7008498 - 财政年份:1999
- 资助金额:
$ 23万 - 项目类别:
MYC DEPENDENT PATHWAYS IN APOPTOSIS AND LYMPHOMAGENESIS
细胞凋亡和淋巴生成中的 MYC 依赖性途径
- 批准号:
6626634 - 财政年份:1999
- 资助金额:
$ 23万 - 项目类别:
MYC DEPENDENT PATHWAYS IN APOPTOSIS AND LYMPHOMAGENESIS
细胞凋亡和淋巴生成中的 MYC 依赖性途径
- 批准号:
6489192 - 财政年份:1999
- 资助金额:
$ 23万 - 项目类别:
Myc Oncogene Mutations and Polymorphisms in Cancer
癌症中的 Myc 癌基因突变和多态性
- 批准号:
7995269 - 财政年份:1999
- 资助金额:
$ 23万 - 项目类别:
MYC Dependent Pathways in Apoptosis and Lymphomagenesis
细胞凋亡和淋巴瘤发生中的 MYC 依赖性途径
- 批准号:
6733843 - 财政年份:1999
- 资助金额:
$ 23万 - 项目类别:
Myc Oncogene Mutations and Polymorphisms in Cancer
癌症中的 Myc 癌基因突变和多态性
- 批准号:
7783140 - 财政年份:1999
- 资助金额:
$ 23万 - 项目类别:
Myc Oncogene Mutations and Polymorphisms in Cancer
癌症中的 Myc 癌基因突变和多态性
- 批准号:
8196898 - 财政年份:1999
- 资助金额:
$ 23万 - 项目类别:
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