STHENOS-b

The project STHENOS-b is a direct continuation of the successful STHENOS project, which focused on the development of bioactive compounds targeting selected therapeutic targets (cancer and aging). The final certification report of STHENOS states characteristically:

“In achieving the above Work Packages, the expertise of all laboratories of the Institute was utilized and leveraged. The Institute had only recently taken its new form in 2012, as a result of the merger of two former Institutes of NHRF. With regard to the research approach, the sequencing of the Work Packages, the exploitation of the results of one Package by the next, as well as their complementarity, led to the successful experimental outcomes of the STHENOS project.
We could say that the structure of this project, from a research perspective, reflects the approach used by pharmaceutical industries for the development of new therapeutic molecules–drugs.
The STHENOS project successfully achieved its aims:
(a) the experiments led to several new, highly promising bioactive molecules;
(b) approximately 30 young researchers worked, were trained, and transferred know-how within the project – some of them also had the opportunity to visit collaborating laboratories abroad;
(c) the results were presented at numerous international conferences and at an international Symposium organized by NHRF in Athens;
(d) publications in peer-reviewed international journals emerged;
(e) Patent Applications were filed.”
It concludes: “Finally, given that the bioactive compounds produced by this research effort are highly promising, it would be extremely important to enable continuation of funding up to the stage at which researchers can propose a new therapeutic molecule–drug.”

The STHENOS-b project aims to further leverage the synergistic activities of IBΦΧΒ for the optimization of targeted bioactive compounds with anticancer and anti-aging properties that were designed, synthesized, and evaluated in the successfully completed STHENOS project. The biological targets include the proteasome, the glucocorticoid receptor, and the mutant oncoproteins BRAF(V600E) and p53(Y220C).

The development of the new compounds will be based on the previously selected targeted bioactive compounds, improved pharmacophore models, and a synergistic combination of computational chemistry, synthetic medicinal chemistry, protein X-ray crystallography, and biological evaluation in model cell lines and animal cancer models (breast, colorectal and melanoma) and aging models.

In parallel, toxicity assessment of the new compounds will be performed, along with an integrated genomic approach to evaluate the response of model cell lines to selected improved compounds, aiming to identify biomarkers of sensitivity and synergy with established therapeutic approaches.

The objective is to enable evaluation of the new compounds in the near future in preclinical suitability studies, with the aim of exploiting them as candidate drugs. To this end, nanodispersion systems will be developed for the efficient encapsulation, active delivery, and targeted action of the new compounds.

The long-term goal of the project is the development of specialized therapeutic and chemoprotective approaches, incorporating the new compounds either directly or in rational combinations with known drugs.