Project Summary

Synthesizing AUF1 inhibitors to treat tumors that express high levels of this pro-metastatic protein.

The AUF1 protein enhances the expression of various oncogenes (c-MYC, IL-6,..) and represses the expression of important tumor suppressor genes (p16, p53,…) through post-transcriptional regulation. The RNA-binding protein AUF1 is highly expressed in various types of tumors and is related to aggressiveness and metastasis.

We have recently shown that AUF1 promotes epithelial-to-mesenchymal transition and enriches the resistant cancer stem cells sub-population. Therefore, the present project aims to synthesize AUF1 inhibitors for treating tumors that express high levels of this pro-metastatic protein. To this end, several AUF1 inhibitors have already been identified at the Cleveland Clinic in collaboration with Dr. Babal Jha. These molecules can bind to different sites of the AUF1 3D structure and are predicted to inhibit the interaction of the protein with the target RNA. Therefore, we are interested in testing the anti-cancer effects of the top hit molecules against various types of cancer cells, which showed expression of high levels of AUF1. The molecules with potent anti-cancer activity will also be tested in vivo on animal models. This will enable the identification of novel effective anti-cancer molecules that will specifically target AUF1-expressing tumors regardless of the organ. This targeted therapy will support the general trend of improving cancer treatment through precision oncology, which is expected to offer fewer and less severe side effects, as well as higher survival rates.

Collaborators

Geno Novo Technologies, Abyss Math Genius Ltd, SciFinance Technologies.

Figures

Figure01 - ANTI-AUF1 Inhibitory Molecules for Precision Therapy
TNL-2020, a potent AUF-1 inhibitor, suppresses the proliferative and invasive/migratory abilities of breast cancer cells.
Figure02 - ANTI-AUF1 Inhibitory Molecules for Precision Therapy
TNL-2020 can target active breast cancer-associated fibroblasts.
Beta Version