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Recent Advances in Kinase Drug Discovery Part I: The Editors’ Take
Article

Structural Basis of Inhibition of DCLK1 by Ruxolitinib

Research Institute, National Cancer Center, Goyang 10408, Gyeonggi, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to the work.
Academic Editors: Manuela Zavatti and Sandra Marmiroli
Int. J. Mol. Sci. 2021, 22(16), 8488; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168488
Received: 1 July 2021 / Revised: 3 August 2021 / Accepted: 3 August 2021 / Published: 6 August 2021
(This article belongs to the Special Issue Advances in Kinase Drug Discovery 2.0)
Given the functional attributes of Doublecortin-like kinase 1 (DCLK1) in tumor growth, invasion, metastasis, cell motility, and tumor stemness, it is emerging as a therapeutic target in gastrointestinal cancers. Although a series of specific or nonspecific ATP-competitive inhibitors were identified against DCLK1, different types of scaffolds that can be utilized for the development of highly selective inhibitors or structural understanding of binding specificities of the compounds remain limited. Here, we present our work to repurpose a Janus kinase 1 inhibitor, ruxolitinib as a DCLK1 inhibitor, showing micromolar binding affinity and inhibitory activity. Furthermore, to gain an insight into its interaction mode with DCLK1, a crystal structure of the ruxolitinib-complexed DCLK1 has been determined and analyzed. Ruxolitinib as a nonspecific DCLK1 inhibitor characterized in this work is anticipated to provide a starting point for the structure-guided discovery of selective DCLK1 inhibitors. View Full-Text
Keywords: doublecortin-like kinase 1; DCLK1; kinase inhibitor; anticancer; structure-based drug discovery; ATP-competitive inhibitor doublecortin-like kinase 1; DCLK1; kinase inhibitor; anticancer; structure-based drug discovery; ATP-competitive inhibitor
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MDPI and ACS Style

Jang, D.M.; Lim, H.J.; Hahn, H.; Lee, Y.; Kim, H.K.; Kim, H.S. Structural Basis of Inhibition of DCLK1 by Ruxolitinib. Int. J. Mol. Sci. 2021, 22, 8488. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168488

AMA Style

Jang DM, Lim HJ, Hahn H, Lee Y, Kim HK, Kim HS. Structural Basis of Inhibition of DCLK1 by Ruxolitinib. International Journal of Molecular Sciences. 2021; 22(16):8488. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168488

Chicago/Turabian Style

Jang, Dong M., Hyo J. Lim, Hyunggu Hahn, Yeon Lee, Hark K. Kim, and Hyoun S. Kim 2021. "Structural Basis of Inhibition of DCLK1 by Ruxolitinib" International Journal of Molecular Sciences 22, no. 16: 8488. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168488

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