Yeast Target-based Assays for Drug Discovery

Creative Biolabs together with partners has developed an unparalleled platform of yeast target-based assays for antibody drug discovery. The use of these assays in the early phase of the screening will greatly reduce the costs and will expedite the discovery of new regulators of specific therapeutic targets. The yeast target-based approach can be highly useful in the first-line screening of potential active compounds to be tested in more complex cell models.

The high degree of cellular processes conservation between the yeast Saccharomyces cerevisiae and higher eukaryotes has made this microorganism a valuable cell model to study the pathobiology of several human diseases. Moreover, the possibility of reproducing the function of disease-associated human proteins without orthologues in yeast has allowed an independent analysis of a wide range of human proteins (or simplified networks of human proteins) in a simpler eukaryotic environment. This humanized yeast model has emerged as a powerful tool in large-scale screenings directed to target human proteins.

Benefits of these assays over other existing technologies include:
a) The possibility to search against a specific molecular target, overcoming the limitation of the traditional drug discovery strategy that implicates the subsequent identification of the drug target, which is a costly and complex task;
b) With a simpler eukaryotic cellular environment, it eliminates the interference of other proteins with similar functions, endogenous regulators and redundant cellular processes;
c) Easier and lower-cost manipulation;
d) Easier and faster propagation in high-throughput screening automated systems;
e) The possibility for an immediate analysis of relevant drug properties, such as cellular permeability, instability and cytotoxicity.

We have specifically developed several yeast target-based assays direct to major therapeutic targets, particularly in cancer:

Select Product Citations

  1. Leão, M., Gomes, S., Soares, J., Bessa, C., Maciel, C., Ciribilli, Y., Pereira, C., Inga, A. and Saraiva, L. (2013) 'Novel simplified yeast-based assays of regulators of p53-MDMX interaction and p53 transcriptional activity', FEBS Journal, 280(24), 6498-6507.
  2. Leão, M., Gomes, S., Pedraza-Chaverri, J., Machado, N., Sousa, E., Pinto, M., Inga, A., Pereira, C. and Saraiva, L. (2013) 'α-Mangostin and Gambogic Acid as Potential Inhibitors of the p53-MDM2 Interaction Revealed by a Yeast Approach', Journal of natural products, 76(4), 774-778.
  3. Pereira, C., Coutinho, I., Soares, J., Bessa, C., Leão, M. and Saraiva, L. (2012) 'New insights into cancer-related proteins provided by the yeast model', FEBS Journal, 279(5), 697-712.

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