| First Author | Ferguson FM | Year | 2020 |
| Journal | Nat Chem Biol | Volume | 16 |
| Issue | 6 | Pages | 635-643 |
| PubMed ID | 32251410 | Mgi Jnum | J:349151 |
| Mgi Id | MGI:7645994 | Doi | 10.1038/s41589-020-0506-0 |
| Citation | Ferguson FM, et al. (2020) Discovery of a selective inhibitor of doublecortin like kinase 1. Nat Chem Biol 16(6):635-643 |
| abstractText | 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. |
