P1/2, N=102, Recruiting, Jacobio Pharmaceuticals Co., Ltd. | Trial completion date: Aug 2026 --> Aug 2027 | Trial primary completion date: Aug 2024 --> Aug 2026

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.

P1/2, N=70, Recruiting, Ellipses Pharma | Trial completion date: Dec 2025 --> Dec 2026

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.].

P1/2, N=26, Terminated, Suzhou Junjing BioSciences Co., Ltd. | N=126 --> 26 | Not yet recruiting --> Terminated; The sponsor terminated the study on the basis of the current data and the company's research and development strategy

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.

Screening of the ZINC database yielded 774 hits, from which A1 (ZINC63106872) and A2 (ZINC39272872) were identified as the top candidates, with superior docking scores (-9.24 and -8.97 kcal/mol) compared to the reference MK-5108 (-7.49 kcal/mol)...RMSF values remained below 2.4 Å. The most favourable binding energy for A1 (-75.34 kcal/mol) in MM-GBSA analysis confirms its strong interaction and therapeutic potential.

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.