Cyclopenta[ b]indole Derivative Inhibits Aurora B in Primary Cells
Artikel i vetenskaplig tidskrift, 2020

The Aurora family of kinases is closely involved in regulating cell division. Inhibition of Aurora A and B with small molecules is currently being investigated in clinical trials for the treatment of different cancers. It has also been evaluated as a treatment option against different autoimmune diseases in preclinical studies. Here, we present a cyclopenta[b]indole derivative capable of inhibiting Aurora B selectively in kinase assays. To evaluate the Aurora B inhibition capacity of the compound, we used a kinase IC50 assay as well as a suppression assay of proliferating primary cells. In addition, we examined if the cells had gained a phenotype characteristic for Aurora B inhibition after treatment with the compound. We found that the compound selectively inhibited Aurora B (IC50 = 1.4 μM) over Aurora A (IC50 > 30 μM). Moreover, the compound inhibited proliferating PBMCs with an IC50 = 4.2 μM, and the cells displayed reduced phosphorylation of histone H3 as well as tetraploidy, consistent with Aurora B inhibition.

Författare

Andreas Ekebergh

Chalmers, Kemi och kemiteknik, Kemi och biokemi

Jerker Mårtensson

Chalmers, Kemi och kemiteknik, Kemi och biokemi

Christine Lingblom Ekebergh

Göteborgs universitet

Sahlgrenska universitetssjukhuset

ACS Omega

24701343 (eISSN)

Vol. 5 51 33455-33460

Ämneskategorier

Cell- och molekylärbiologi

Farmakologi och toxikologi

Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

DOI

10.1021/acsomega.0c05491

PubMed

33403307

Mer information

Senast uppdaterat

2021-02-08