Details

Autor(en) / Beteiligte

• Ferguson, Fleur M
• Nabet, Behnam
• Raghavan, Srivatsan
• Liu, Yan
• Leggett, Alan L
• Kuljanin, Miljan
• Kalekar, Radha L
• Yang, Annan
• He, Shuning
• Wang, Jinhua
• Ng, Raymond W S
• Sulahian, Rita
• Li, Lianbo
• Poulin, Emily J
• Huang, Ling
• Koren, Jost
• Dieguez-Martinez, Nora
• Espinosa, Sergio
• Zeng, Zhiyang
• Corona, Cesear R
• Vasta, James D
• Ohi, Ryoma
• Sim, Taebo
• Kim, Nam Doo
• Harshbarger, Wayne
• Lizcano, Jose M
• Robers, Matthew B
• Muthaswamy, Senthil
• Lin, Charles Y
• Look, A Thomas
• Haigis, Kevin M
• Mancias, Joseph D
• Wolpin, Brian M
• Aguirre, Andrew J
• Hahn, William C
• Westover, Kenneth D
• Gray, Nathanael S

Titel

Discovery of a selective inhibitor of doublecortin like kinase 1

Ist Teil von

• Nature chemical biology, 2020-06, Vol.16 (6), p.635

Ort / Verlag

United States

Erscheinungsjahr

2020

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.