Hesperadin is an ATP Competitive Indolinone Inhibitor of Aurora A and B

Aurora kinases (AURK) are a group of serine/threonine kinases. And they participate in the cellular division through the regulation of chromatid segregation. what’s more, AURK has three subclasses: AURKA, AURKB, and AURKC. In this article, we will introduce a potent inhibitor of Aurora A and B, Hesperadin.

As an ATP competitive indolinone inhibitor of Aurora A and B. Hesperadin inhibits Aurora B with an IC50 of 250 nM.

Hesperadin is an ATP Competitive Indolinone Inhibitor of Aurora A and B 2022 02 17 02 scaled - Hesperadin is an ATP Competitive Indolinone Inhibitor of Aurora A and B

Additionally, Hesperadin inhibits the growth of Trypanosoma brucei by blocking nuclear division and cytokinesis.

In M110 cells, Hesperadin inhibits the Aurora kinase-1 (TbAUK1)-mediated phosphorylation of trypanosome histone H3 (TbH3). Besides, it inhibits p-TbH3 in a dose-dependent manner, with an IC50 of 40 nM.
And, Hesperadin inhibits the growth of bloodstream forms (BF) and procyclic forms (PF) cultures. What’s more, it inhibits the growth of BF cultures with IC50 of 50 nM. While the inhibition of PF growth required approximately 11-fold more Hesperadin, with IC50 of 550 nM.

In a Cell Cycle Analysis, Hesperadin alters cell morphology and inhibits cell cycle progression similar to the RNAi knockdown of TbAUK.

As well known, kinases function extensively as signals transmission. Aberrant expression or activation of kinases may result in the oncogenesis of a wide range of cancers. Besides, treatment targeting kinases is an efficient way for tumor proliferation reduction. Additionally, Recent studies show that AURKB contributes to the development and progression of various tumors.
Furthermore, Aberrant elevation of AURKB leads to unequal chromosomal separation in cell division then causes abnormal numbers of chromosomes in a single cell, which is an initial event during cancer development.

In a 6-week-old female nude mice injected GBM cells, Hesperadin increases the survival of xenograft mice models. And it prolongs the survival of xenograft mice via synergistic effect with temozolomide (TMZ).

In conclusion, Hesperadin is a potent Aurora A/B inhibitor. It can be used for tumor research. And Hesperadin also is a broad-spectrum influenza antiviral.

Reference:

[1]. Neal J, et, al. Mol Microbiol. 2009 Apr; 72(2): 442-58.

[2]. Hu Y, et, al. Int J Mol Sci. 2017 Sep 8;18(9):1929.