Mutation of RAS genes is a critical event in the pathogenesis of different human tumors and in some developmental disorders. Here we present an arabinose-derived bicyclic compound displaying selective cytotoxicity in human colorectal cancer cells expressing K-RasG13D, that shows high intrinsic nucleotide exchange rate. We characterize binding of bicyclic compounds by docking and NMR experiments and their inhibitory activity on GEF-mediated nucleotide exchange on wild-type and mutant Ras proteins. We demonstrate that the in vitro inhibition of Ras nucleotide exchange depends on the molar ratio between Ras and its GEF activator, suggesting that the observed in vivo selective effect may depend on biochemical parameters and actual intracellular concentration of the Ras protein and its regulators
Palmioli, A., Sacco, E., Airoldi, C., Di Nicolantonio, F., D’Urzo, A., Shirasawa, S., et al. (2009). Selective cytotoxicity of a bicyclic Ras inhibitor in cancer cells expressing K-RasG13D. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 386(4), 593-597.
Citazione: | Palmioli, A., Sacco, E., Airoldi, C., Di Nicolantonio, F., D’Urzo, A., Shirasawa, S., et al. (2009). Selective cytotoxicity of a bicyclic Ras inhibitor in cancer cells expressing K-RasG13D. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 386(4), 593-597. |
Tipo: | Articolo in rivista - Articolo scientifico |
Carattere della pubblicazione: | Scientifica |
Titolo: | Selective cytotoxicity of a bicyclic Ras inhibitor in cancer cells expressing K-RasG13D |
Autori: | Palmioli, A; Sacco, E; Airoldi, C; Di Nicolantonio, F; D’Urzo, A; Shirasawa, S; Sasazuki, T; Di Domizio, A; De Gioia, L; Martegani, E; Bardelli, A; Peri, F; Vanoni, ME |
Autori: | |
Data di pubblicazione: | 18-giu-2009 |
Lingua: | English |
Rivista: | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1016/j.bbrc.2009.06.069 |
Appare nelle tipologie: | 01 - Articolo su rivista |
File in questo prodotto:
File | Descrizione | Tipologia | Licenza | |
---|---|---|---|---|
mmc1.doc | N/A | Open Access Visualizza/Apri |