SP-146 is a Selective and non-ATP-Competitive Aurora B Inhibitor
Posted On 2020-08-19
Aurora B Kinase is a serine-threonine kinase and plays an important role in mitosis. This kinase also plays an important role in mitosis as a serine-threonine kinase. It also a part of the chromosomal passenger complex (CPC). Overexpression of Aurora B has been reported in several cancers, such as colorectal cancer, prostate cancer, and lung cancer.
As a result, cancer research focuses on the inhibition of Aurora kinase B and result in a few promising molecules, such as SP-96 and SP-146. etc al.
In this article, we will introduce a potent Aurora B inhibitor, SP-146.
SP-146 is a highly potent, selective, and non-ATP-competitive Aurora B inhibitor with an IC50 of 0.316 nM. SP-146 can be used for the research of triple-negative breast cancer (TNBC).
In NCI60 screening, SP-146 inhibits cell growth in a concentration-dependent manner. It is not promiscuous, rather selective for a few cell lines, such as breast cancer cells. SP-146 inhibits MDA-MB-468, CCRF-CEM, COLO 205 and A498 cell growth with GI50 values of 107 nM,47.4 nM, 50.3 nM and 53.2 nM, respectively.
In H460 cells, SP-146 (63.2 nM) inhibits Aurora B activity by the characteristics of increased DNA content, and it increases cell volume with an enormous nucleus. Besides, in kinase assay, SP-146 (0-2 µM) inhibits Aurora B enzymatic activity with an IC50 of 0.316 nM and inhibits Aurora A with observed IC50 value of 18.975 nM. It shows >2000 fold selectivity against FLT3 (IC50=1475.6 nM) and KIT (IC50=1307.6 nM). Meanwhile, this inhibitor exhibits inhibitory effects on other receptor tyrosine kinases (RTKs) namely EGFR, RET, and HER2 with IC50 value ≥2 µM.
In conclusion, SP-146 is a novel Aurora Kinase B inhibitor and shows an improved selectivity profile compared to Barasertib. SP-146 exhibits growth inhibition of selective NCI60 cell lines, including MDA-MB-468. SP-146 will serve as an excellent lead compound for Aurora B inhibition and cancer study.
Naga Rajiv Lakkaniga,et al. Eur J Med Chem. 2020 Jul 12;203:112589.