AurkA allosteric-IN-1 (compound 6h) is an Aurora A (AurkA) inhibitor with an IC50 of 6.50 μM, which inhibits both the catalytic and non-catalytic activities of Aurora A. Aurora A is involved in the regulation of bipolar mitotic spindle assembly and the fidelity of chromosome segregation during mitosis. AurkA allosteric-IN-1 interferes with Aurora A by binding to the Y-pocket, thereby preventing its interaction with the activator TPX2.

Aurora A:6.5 μM

AurkA allosteric-IN-1 demonstrates varying effects on cell cycle arrest across different cell types, including lung and colorectal cancer cell lines, at a concentration of 100 μM over 48 hours. At 20 μM for the same duration, it downregulates histone H3 phosphorylation in cancer cells. Additionally, AurkA allosteric-IN-1 exhibits significant antiproliferative activity against HeLa cells at concentrations ranging from 25 to 400 μM over 48 hours and shows synergistic effects with PHA-767491, enhancing its antiproliferative efficacy further.