Cyclopenta[b]indole Derivative Inhibits Aurora B in Primary Cells
| Autor: | Jerker Mårtensson, Christine Lingblom Ekebergh, Andreas Ekebergh |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Indole test
Cell division Kinase Chemistry General Chemical Engineering Aurora B kinase macromolecular substances General Chemistry Small molecule Molecular biology Article enzymes and coenzymes (carbohydrates) Histone H3 embryonic structures Phosphorylation biological phenomena cell phenomena and immunity QD1-999 IC50 |
| Zdroj: | ACS Omega ACS Omega, Vol 5, Iss 51, Pp 33455-33460 (2020) |
| ISSN: | 2470-1343 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|