alisertib (MLN8237)

P1, N=24, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

P2, N=96, Completed, Mayo Clinic | Active, not recruiting --> Completed

The results demonstrated the potential of using cilia-promoting drugs, such as Alvocidib and Alisertib, to suppress cancer cell replication. Additionally, it shows the massive benefits of integrating accessible large language models to conduct sweeping, rapid, and accurate literature searches.

Our findings suggest that Res may regulate BCa cell expression through the AURKA/STAT3 axis, providing a theoretical foundation for the structural optimization of Res and the development of multi-target drugs for clinical application.

In vitro validation narrowed compounds of interest to raltitrexed, alisertib, GTX-007, LY315920, and PD0325901. Treatment with alisertib leads to decrease in H2AK119ub and shift in the immune tumor microenvironment. Alisertib efficacy in HGSC is dependent on functional CBX2 and cell target engagement confirms selectivity for CBX2, supporting that alisertib activity involves CBX2 inhibition.

In addition, we review the status of AURKA-specific inhibitors in clinical evaluation and their associated adverse effects. Finally, we cite the emerging therapeutic strategy of proteolysis targeting chimeras (PROTACs) as an innovative means to selectively degrade AURKs, offering a novel approach to targeted cancer therapy.

In this study, we report the development of CCT400028, a second-generation alisertib-derived Aurora A PROTAC...Potent Aurora A degradation was shown in three pediatric tumor cell lines, as well as excellent selectivity and on-target mechanism of action. CCT400028 and a matched inactive control analogue fulfill the criteria for a degrader chemical probe for studying Aurora A degradation in vitro.

PGCCs contributed to alisertib insensitivity in TNBCs that may be targeted by mifepristone.

The MD over 200 ns indicated that marine compounds, such as Shellmycin C (CID:156581889) and Rhodoptilometrin (CID:625242), displayed significantly greater stability compared to the control drug Alisertib (CID:24771867). Consequently, these findings underscore the potential for developing innovative therapeutic strategies that target the AURKA-TPX2 complex in LUAD, warranting further validation through in vitro and in vivo studies. The online version contains supplementary material available at 10.1007/s40203-025-00436-z.

Alisertib enables both normal and transformed cells with high levels of survivin to activate the APC/C prematurely, as observed by the destruction of cyclin B and securin. Thus, a high expression of survivin can alter cell fate decisions at mitosis and lead to genetic instability, a key hallmark in cancer.

[This retracts the article DOI: 10.2147/DDDT.S74127.].

[This retracts the article DOI: 10.2147/DDDT.S75378.].