Nausicaa Orteca

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GBP1 and PIM1 are known to interact with a molar ratio 1:1. GBP1:PIM1 binding initiates a signaling pathway that induces resistance to common chemotherapeutics such as paclitaxel. Since GBP1 is a large GTPase which undergoes conformational changes in a nucleotide-dependent manner, we investigated the effect of GTP/GDP binding on GBP1:PIM1 interaction by(More)
Class III β-tubulin plays a prominent role in the development of drug resistance to paclitaxel by allowing the incorporation of the GBP1 GTPase into microtubules. Once in the cytoskeleton, GBP1 binds to prosurvival kinases such as PIM1 and initiates a signaling pathway that induces resistance to paclitaxel. Therefore, the inhibition of the GBP1:PIM1(More)
As a continuation of our efforts to develop innovative ligands for D(3), 5-HT(1A), and 5-HT(2A) receptors with low propensity to block hERG channels, we propose a series bishetero(homo)arylpiperazines 5a-m as novel and potent multifunctional ligands characterized by low occupancy at D(2) and 5-HT(2C) receptors.
The novel tetrasubstituted pyrrole derivatives 8g, 8h, and 8i showed selective cytotoxicity against M14 melanoma cells at low micromolar concentration. Structure-activity relationships (SARs) indicated the presence of three aromatic substituents on the pyrrole core as necessary for biological activity. Computational studies strongly suggest that the(More)
Bcl-2 plays a prominent role in regulating the function of mitochondria during respiration and in determining the threshold of apoptotic sensitivity. Despite its relevance, the mechanism through which these processes are achieved is still unknown. Using surface plasmon resonance technology to monitor Bcl-2 multimerisation we discovered that a simple dimeric(More)
The majority of functionally important biological processes are regulated by allosteric communication within individual proteins and across protein complexes. The proteins controlling these communication networks respond to changes in the cellular environment by switching between different conformational states. Targeting the interface residues mediating(More)
An integrated computational approach, based on molecular dynamics/mechanics, semi-empirical, and DFT calculations as well as dynamic docking studies, has been employed to gain insight into the mechanism of action of new antimalarial agents characterized by the scaffold of the marine compounds plakortin and aplidinone. The results of this approach show that(More)
Computer-aided drug discovery plays a strategic role in the development of new potential therapeutic agents. Nevertheless, the modeling of biological systems still represents a challenge for computational chemists and at present a single computational method able to face such challenge is not available. This prompted us, as computational medicinal chemists,(More)
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