1. Reply to Oegema et al.: CFI-400945 and Polo-like kinase 4 inhibition
- Author
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Tak W. Mak, Xi Liu, Jason Roszik, David W. Cescon, Kelsie L. Thu, Jonathan M. Kurie, Jaime Rodriguez-Canales, Ethan Dmitrovsky, Yulong Chen, Barbara Mino, Jennifer Silvester, Masanori Kawakami, Pamela Villalobos, Ignacio I. Wistuba, Lisa Maria Mustachio, and Lin Zheng
- Subjects
0301 basic medicine ,PLK4 ,Indazoles ,Indoles ,Lung Neoplasms ,Multidisciplinary ,Chemistry ,Kinase ,Aurora B kinase ,Polo-like kinase ,Centrinone ,Polyploidy ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Cancer research ,Humans ,Letters - Abstract
In “CFI-400945 is not a selective cellular PLK4 inhibitor,” Oegema et al. (1) raise thoughtful comments about our article (2). We appreciate their interest and critique. They propose that CFI-400945 activity was not from Polo-like kinase (PLK4) inhibition and argue that antineoplastic activity was through Aurora B kinase (1), rather than PLK4 inhibition (2). Kinases often share related catalytic pockets, and targeting one kinase without affecting another is difficult to achieve. This is true for CFI-400945 (2) and centrinone, the PLK4 inhibitor (3) used by Oegema et al. (1). CFI-400945 is (by IC50) 38-fold more potent in causing PLK4 inhibition than in antagonizing Aurora B kinase (4, 5). Despite their claim … [↵][1]1Email: tak.mak{at}uhnresearch.ca. [1]: #xref-corresp-1-1
- Published
- 2018
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