期刊
NATURE CHEMICAL BIOLOGY
卷 16, 期 6, 页码 635-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41589-020-0506-0
关键词
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资金
- American Cancer Society Postdoctoral Fellowship [PF-17-010-01-CDD]
- Claudia Adams Barr Program in Innovative Basic Cancer Research Award
- Katherine L. and Steven C. Pinard Research Fund
- Hope Funds for Cancer Research Postdoctoral Fellowship
- Harvard Catalyst KL2/CMeRIT Fellowship
- Perry Levy Fellowship
- Lustgarten Foundation
- NCI HCMI program
- American Cancer Society [129089-PF16-088-01-TBG, 132205-RSG-18-039-01-DMC]
- KU-KIST Graduate School of Converging Science and Technology Program
- Spanish Ministerio de Economia y Competitividad [SAF2015-60268R]
- Fondo Europeo de Desarrollo Regional funds
- Pancreatic Cancer Action Network Catalyst Award
- Doris Duke Charitable Foundation Clinician Scientist Development Award
- NCI [K08 CA218420, U01 CA176058, U01 CA199253, U01 CA224146]
- Welch Foundation [I1829]
- 2017 AACR-Bayer Innovation and Discovery grant [17-80-44-GRAY]
- DF/HCC GI SPORE Developmental Research Project [P50CA127003]
- Hale Center for Pancreatic Research
Doublecortin like kinase 1 (DCLK1) is an understudied kinase that is upregulated in a wide range of cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about its potential as a therapeutic target. We used chemoproteomic profiling and structure-based design to develop a selective, in vivo-compatible chemical probe of the DCLK1 kinase domain, DCLK1-IN-1. We demonstrate activity of DCLK1-IN-1 against clinically relevant patient-derived PDAC organoid models and use a combination of RNA-sequencing, proteomics and phosphoproteomics analysis to reveal that DCLK1 inhibition modulates proteins and pathways associated with cell motility in this context. DCLK1-IN-1 will serve as a versatile tool to investigate DCLK1 biology and establish its role in cancer.
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