Inducing Protein Degradation: A New Pharmaceutical Paradigm
诱导蛋白质降解:新的制药范例
基本信息
- 批准号:8955987
- 负责人:
- 金额:$ 84.99万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-09-09 至 2022-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcademiaAddressAntineoplastic AgentsCell Culture TechniquesChimera organismDevelopmentDiseaseDrug IndustryDrug TargetingDrug usageFDA approvedFutureGenomicsMultiple MyelomaNuclear Hormone ReceptorsOncogene ProteinsOncogenicPharmaceutical PreparationsPharmacologic SubstancePlayProteasome InhibitorProteinsProteolysisRecruitment ActivityRefractoryRelapseResearchSmall Interfering RNATechnologyTranslatinganticancer researchbasebench to bedsidedrug developmentin vivoinnovationnoveloncologyprotein degradationpublic health relevancesmall moleculesuccesstranscription factorubiquitin-protein ligasewasting
项目摘要
DESCRIPTION (provided by applicant): The pharmaceutical industry is in a crisis; unfortunately the post-genomic era has not significantly changed the number of proteins pursued by drug companies. This dearth of new cancer drug targets has resulted in too many `me too' drugs and wasted effort. To address this need, my lab has focused on developing the new field of `Controlled Proteostasis'. Our initial efforts focused on inhibiting protein turnover;
we developed a novel proteasome inhibitor, YU101, which served as the basis of a new oncology-based biopharma, Proteolix, Inc. from my lab. Ultimately, YU101 became carfilzomib/Kyprolis(r), which was approved by the FDA in 2012 for relapsed/refractory multiple myeloma. More recently, my lab has been focused on the flipside of protein turnover, i.e., developing a small molecule analogy to siRNA to induce protein knockdown. We have shown that this strategy, known as Proteolysis Targeting Chimerae (PROTACs) can effectively recruit targeted oncoproteins to E3 ubiquitin ligases for induced degradation, both in cell culture and in vivo. Having founded another biopharma, Arvinas, Inc., to focus on the application of this approach to nuclear hormone receptors in oncology, I propose here to develop this technology further to target truly undruggable proteins that are key oncogenic drivers. This innovative approach of `induced protein degradation' has the potential to be a new drug development paradigm that could have a significant impact by dramatically expanding the protein classes one can target pharmaceutically. Finally, for the past 19 years, I have focused on translating research from my lab into both new oncology-focused ventures and a FDA-approved drug, thus demonstrating truly `bench-to-bedside' research that is not common in academia today. This track record of innovation and execution within translational cancer research are strong predictors of continued future success.
项目成果
期刊论文数量(0)
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{{ truncateString('CRAIG M CREWS', 18)}}的其他基金
Inducing Proximity: An Emerging Paradigm for New Therapeutic Modalities
诱导接近:新治疗方式的新兴范例
- 批准号:
10518541 - 财政年份:2015
- 资助金额:
$ 84.99万 - 项目类别:
Inducing Protein Degradation: A New Pharmaceutical Paradigm
诱导蛋白质降解:新的制药范例
- 批准号:
9142301 - 财政年份:2015
- 资助金额:
$ 84.99万 - 项目类别:
Inducing Protein Degradation: A New Pharmaceutical Paradigm
诱导蛋白质降解:新的制药范例
- 批准号:
10250394 - 财政年份:2015
- 资助金额:
$ 84.99万 - 项目类别:
Inducing Protein Degradation: A New Pharmaceutical Paradigm
诱导蛋白质降解:新的制药范例
- 批准号:
9763483 - 财政年份:2015
- 资助金额:
$ 84.99万 - 项目类别:
Inducing Proximity: An Emerging Paradigm for New Therapeutic Modalities
诱导接近:新治疗方式的新兴范例
- 批准号:
10701073 - 财政年份:2015
- 资助金额:
$ 84.99万 - 项目类别:
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