Chemical Proteomic Platforms for Radically Expanding Cancer Druggability
用于从根本上扩展癌症成药性的化学蛋白质组学平台
基本信息
- 批准号:10248401
- 负责人:
- 金额:$ 116.1万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-01 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:Basic ScienceBiologicalBiological Response Modifier TherapyBiologyCellsChemicalsCodeDNA sequencingDevelopmentFutureGoalsHumanHuman GeneticsImmuneImmunologyImmunooncologyKnowledgeMalignant NeoplasmsMapsMedicineMethodsModernizationMolecularMutateNatural ImmunityOncogenesPharmacologyPlayProteinsProteomeProteomicsResearchRoleSystemTechnologyTherapeuticTranslatingTranslational ResearchValidationactivity-based protein profilingadaptive immunityanticancer researchbiological systemscancer cellcancer therapygene discoverygenetic informationinnovationinsightnovel therapeuticsprogramsprotein degradationsmall moleculesmall molecule librariestumor immunologytumorigenesisubiquitin-protein ligase
项目摘要
Cancer research and treatment have greatly benefited from advances in DNA sequencing methods, which
have accelerated the discovery of genes that, when mutated, promote tumorigenesis. The protein products of
some of these oncogenes have served as direct targets for groundbreaking new medicines. Many oncogenes,
however, code for proteins that lack chemical probes and are even considered undruggable. In these cases,
our understanding of the molecular basis of cancer has not yet translated into effective new therapies. A similar
gap can be found in cancer-related immunology (or immuno-oncology), where human genetics is discovering
proteins that play fundamental roles in innate and adaptive immunity; yet, again, most of these proteins lack
chemical probes. A critical challenge has thus emerged in cancer research – how can the massive gains in
understanding of cancer and immunology bequeathed by modern human genetics be translated into new
therapies for cancer? The goal of this research program is to leverage and extend our lab’s innovative activity-
based protein profiling (ABPP) technology to radically expand the druggable content of the human proteome
and develop high-quality chemical probes for genetically-defined protein targets in cancer and immuno-
oncology. We have recently introduced advanced ABPP platforms that evaluate small-molecule interactions
across thousands of proteins in parallel directly in native biological systems. By combining proteome-wide
druggability maps of human cancer and immune cells furnished by ABPP with human genetic information, we
have identified several high-priority cancer targets poised for chemical probe development. Optimized chemical
probes will be used by our lab and a set of expert biology collaborators to characterize the functional relevance
of protein targets in cancer and cancer-related immunology. We will also describe plans for continued
technology innovation to further enhance chemical probe and target discovery by ABPP, including the following
objectives – i) identify newly druggable E3 ligase systems capable of supporting targeted protein degradation
in cancer cells; ii) discover chemical probes that selectively engage modified states of protein targets in cancer
cells; and iii) generate advanced chemical libraries for ABPP to further increase the druggable fraction of the
human cancer proteome. In summary, our research program should deliver high-quality chemical probes for,
and pharmacological validation of, biologically compelling human cancer targets, providing critical knowledge
to direct the future development of transformative cancer therapeutics. More generally, we envision that our
research program will inspire chemical and cancer biologists to embrace the potential druggability of any
human protein, as well as provide an experimental roadmap to realize this goal, for the benefit of both basic
and translational research.
癌症研究和治疗极大地受益于DNA测序方法的进步
项目成果
期刊论文数量(0)
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BENJAMIN F CRAVATT其他文献
BENJAMIN F CRAVATT的其他文献
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{{ truncateString('BENJAMIN F CRAVATT', 18)}}的其他基金
A platform to identify in vivo targets of covalent cancer drugs in 3D tissues
识别 3D 组织中共价癌症药物体内靶标的平台
- 批准号:
10714543 - 财政年份:2023
- 资助金额:
$ 116.1万 - 项目类别:
Integrated ligand and target discovery by chemical proteomics for glioblastoma treatment.
通过化学蛋白质组学整合配体和靶点发现用于胶质母细胞瘤治疗。
- 批准号:
10652580 - 财政年份:2021
- 资助金额:
$ 116.1万 - 项目类别:
Integrated ligand and target discovery by chemical proteomics for glioblastoma treatment.
通过化学蛋白质组学整合配体和靶点发现用于胶质母细胞瘤治疗。
- 批准号:
10436295 - 财政年份:2021
- 资助金额:
$ 116.1万 - 项目类别:
Integrated ligand and target discovery by chemical proteomics for glioblastoma treatment.
通过化学蛋白质组学整合配体和靶点发现用于胶质母细胞瘤治疗。
- 批准号:
10211553 - 财政年份:2021
- 资助金额:
$ 116.1万 - 项目类别:
RP5: Chemical proteomic discovery of small-molecule probes for autophagy proteins
RP5:自噬蛋白小分子探针的化学蛋白质组学发现
- 批准号:
10364727 - 财政年份:2019
- 资助金额:
$ 116.1万 - 项目类别:
RP5: Chemical proteomic discovery of small-molecule probes for autophagy proteins
RP5:自噬蛋白小分子探针的化学蛋白质组学发现
- 批准号:
10573265 - 财政年份:2019
- 资助金额:
$ 116.1万 - 项目类别:
Chemical Proteomic Platforms for Radically Expanding Cancer Druggability
用于从根本上扩展癌症成药性的化学蛋白质组学平台
- 批准号:
10477261 - 财政年份:2018
- 资助金额:
$ 116.1万 - 项目类别:
Chemical Proteomic Platforms for Radically Expanding Cancer Druggability
用于从根本上扩展癌症成药性的化学蛋白质组学平台
- 批准号:
10693197 - 财政年份:2018
- 资助金额:
$ 116.1万 - 项目类别:
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