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Br J Haematol. 2015 Nov;171(3):378-86. doi: 10.1111/bjh.13595. Epub 2015 Aug 3.

The novel atypical retinoid ST5589 down-regulates Aurora Kinase A and has anti-tumour activity in lymphoma pre-clinical models.

Author information

Lymphoma and Genomics Research Program, IOR Institute of Oncology Research, Bellinzona, Switzerland.
Dalle Molle Institute for Artificial Intelligence (IDSIA), Manno, Switzerland.
SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
IOSI Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Research & Development, Sigma-Tau, Pomezia, Italy.


Despite the marked improvements in the treatment of lymphomas, there is still a need for new therapeutic agents. Synthetic retinoids represent a class of compounds with anti-cancer activity. Here, we report the preclinical activity of a new member of this class, the ST1926-derivative ST5589, in lymphomas. ST5589 presented a dose-dependent anti-proliferative activity in almost all of the 25 lymphoma cell lines analysed, with a median 50% inhibitory concentration of 433 nM. Apoptosis was observed in 8/11 cell lines. ST5589 induced changes in the gene expression profiles of the cell lines, including the down-regulation of Aurora Kinase A (AURKA). Specific gene expression signatures were associated with a higher sensitivity to the compound and combination of ST5589 with carfilzomib revealed the importance of proteasome activity in mediating the anti-tumour activity of ST5589. In conclusion, we have identified a new mechanism of action of atypical retinoids as anti-cancer compounds, and the encouraging results obtained with the new ST1926-derivative ST5589 provide the basis for further developments of the compound.


MYC; ST1926; aurora kinase; lymphomas; new drugs for lymphoma; retinoids

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