IC50: 44 and 19 nM respectively for Aurora A and B in cancer cells
Ki: 8.0 and 9.2 nM for aurora A and B, respectively
The aurora kinases are a family of serine-threonine kinases that interact with components of the mitotic apparatus and that regulate aspects of centrosome maturation, bipolar spindle assembly, chromosome segregation, and cytokinesis. CYC116 has been discoverd as a novel N-phenyl-4-(thiazol-5-yl) pyrimidin-2-amine aurora kinase inhibitor.
In vitro: The anticancer effects of CYC116 were shown to emanate from cell death following mitotic failure and increased polyploidy as a consequence of cellular inhibition of aurora A and B kinases. Moreover, CYC116 was also assessed against other kinases [1].
In vivo: Preliminary in vivo assessment showed that CYC116 was orally bioavailable and possessed anticancer activity. The mean relative tumor volumes of mice receiving CYC116 at both dose levels were less than those of vehicle-treated mice for the duration of the study period [1].
Clinical trials: CYC116 is currently undergoing evaluation in Phase I clinical trials.
Reference:
[1] Wang S, Midgley CA, Scaërou F, Grabarek JB, Griffiths G, Jackson W, Kontopidis G, McClue SJ, McInnes C, Meades C, Mezna M, Plater A, Stuart I, Thomas MP, Wood G, Clarke RG, Blake DG, Zheleva DI, Lane DP, Jackson RC, Glover DM, Fischer PM. Discovery of N-phenyl-4-(thiazol-5-yl)pyrimidin-2-amine aurora kinase inhibitors. J Med Chem. 2010;53(11):4367-78.