alisertib (MLN8237)

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.S75378.].

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

Three were shown to be beneficial after validation: rucaparib, belinostat and alisertib. The Aurora Kinase A inhibitor alisertib in particular led to an over 4-fold increase in preferential gene correction over gene knock-out in two cell models (HEK293T and Hepa 1-6) at sub-micromolar dosages on the eGFP locus, prompting further validation. On the long term this pathway did show cytotoxicity especially in the HEK293T cells, indicating further mechanistic investigation is needed, but this toxicity was less pronounced in primary hepatocytes.

Chemotherapy with cisplatin (CDDP) and etoposide (ETO) is the standard treatment for gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC)...Here, we evaluated Aurora kinase inhibition with alisertib (ALI) as a synthetic lethality strategy in ARID1A-deficient GEP-NEC...These findings establish Aurora kinase inhibition as mechanistically distinct and selectively effective in ARID1A-deficient GEP-NEC. Given its efficacy, favorable tolerability, and ARID1A-dependent specificity, ALI may represent a promising alternative to platinum-based chemotherapy, offering a strong rationale for further development of mechanism-driven combination strategies for GEP-NEC.

Further, Aurora-A inhibitor Alisertib enhanced the sensibility of HCC cells to anti-PD-1 therapy and CD45+CD8+ T cell infiltration in HCC tumors. To conclude, our work revealed that Aurora-A dysregulated PS/PE metabolism via facilitating Drp1-Ser616 phosphorylation to disrupt MAMs formation, resulting in suppressed ferroptosis in HCC cells to reduce their sensitivity to anti-PD-1.

It also exhibited strong antiproliferative effects in gastric cancer cell lines and superior efficacy in patient-derived gastric cancer organoids (IC50 = 3.5 μM), outperforming Alisertib. These findings suggest that compound 11 is a highly potent and selective Aurora A inhibitor with significant therapeutic potential for gastric cancer treatment.

By integrating preclinical in vitro and in vivo models, including cell lines and patient-derived xenografts, with RNA sequencing, we investigated the impact of TAZ overexpression in cetuximab resistance driven by the AURKA/YAP1 axis...Treatment with alisertib, a phase III AURKA inhibitor, simultaneously destabilizes YAP1 and TAZ, restoring anti-EGFR efficacy by suppressing stemness. Transcriptomic analyses further show that AURKA inhibition and dual YAP1/TAZ suppression disrupt stem-like traits and reveal transcriptional deregulations affecting nucleotide metabolism. These findings demonstrate that AURKA orchestrates YAP1/TAZ crosstalk, which is crucial for driving stemness and resistance to anti-EGFR therapies, highlighting AURKA inhibitors as a promising strategy to enhance anti-EGFR therapies in metastatic CRC.