New Arsenic Composition Inhibited Ras Excessive Activation And Its Toxicity

As2O3has been clinical applied to treat APL, but it was restricted for inducing QT prolongation. Synergistic effect may be gain with the method of combination thrapy. Moreover, the side effect can be decreased with composition.A model organism, Caenorhabditis elegans, was used in screening drugs. At first, the anti-ras excessive activity of As2O3, As4S4and realgar leaching solution made by our lab were compared. Realgar leaching solution had significant effects in anti-ras excessive activity, better than AS4S4. AS2O3was useless in inhibiting ras excessive activity. On the other side, exposed to AS4S4and AS2O3, C. elegans pharynx pumping times in30s decreased dramatically. C. elegans pharynx pumping times in30s maintained exposed to realgar leaching solution.The composition was combined with arsenicals(including As2O3, As4S4and realgar leaching solution respectively) and paeonol. It was aimed to screen optimal composition with synergistic effect in anti-ras excessive activity with the method of orthogonal transformation. C. elegans pharynx pumping times in30s was counted to measure the side effects of inducing QT prolongation. The toxicity of the optimal composition was evaluated. The result showed the optimal composition was combined with realgar leaching solution and paeonol. The composition showed significant effects in the inhibition of excessive activation of ras (RBS concentration was4μg/ml, paeonol concentration was100μg/ml). The effects of anti-ras excessive activation was increased40%of the composition. The side effects of QT, LC50, the time for mature, genetic toxicity were evaluted. The concentration of arsenical in the composition was half of realgar leaching solution used only, but showed similar effects.