Computational Analysis and Experimental Testing of the Molecular Mode of Action of Gatastatin and Its Derivatives

Publication: Cancer
Software: ADMET Predictor®


Given its critical role in cell mitosis, the tubulin chain represents a viable chemotherapeutic target to solve the specificity issues associated with targeting and tubulin. Since tubulin is overexpressed in glioblastoma multiforme (GBM) and some breast lesions, the glaziovianin A derivative gatastatin, presented as a -tubulin-specific inhibitor, could yield a successful therapeutic strategy. The present work aims to identify the binding sites and modes of gatastatin and its derivatives through molecular-docking simulations. Computational binding free energy predictions were compared to experimental microscale thermophoresis assay results. The computational simulations did not reveal a strong preference toward tubulin, suggesting that further derivatization may be needed to increase its specificity.

By Paola Vottero, Qian Wang, Marek Michalak, Maral Aminpour and Jack Adam Tuszynski