Potent Irreversible Inhibitors of LasR Quorum Sensing in <i>Pseudomonas aeruginosa</i>
作者:Kevin T. O’Brien、Joseph G. Noto、Luke Nichols-O’Neill、Lark J. Perez
DOI:10.1021/ml500459f
日期:2015.2.12
Antagonism of quorumsensing represents a promising new antivirulence approach for the treatment of bacterial infection. The development of a novel series of non-natural irreversible antagonists of P. aeruginosa LasR is described. The lead compounds identified (25 and 28) display potent LasR antagonist activity and inhibit expression of the P. aeruginosa virulence factors pyocyanin and biofilm formation
The present invention relates to substituted triazole compounds and compositions comprising substituted triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a substituted triazole compound of the invention, or a pharmaceutical composition comprising such a compound.
The present invention relates to substituted triazole compounds and compositions comprising substituted triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a substituted triazole compound of the invention, or a pharmaceutical composition comprising such a compound.
The present invention relates to a molecule having binding specificities for (a) CD123; (b) CD16 and (c) CD33. The present invention further relates to the molecule of the invention, wherein the molecule comprises a first immunoglobulin domain comprising a VL domain linked to a VH domain, wherein the immunoglobulin domain specifically binds to CD123; a second immunoglobulin domain comprising a VL domain linked to a VH domain, wherein the immunoglobulin domain specifically binds to CD16; and a third immunoglobulin domain comprising a VL domain linked to a VH domain, wherein the immunoglobulin domain specifically binds to CD33. The present invention furthermore relates to a nucleic acid molecule encoding the molecule of the invention. In addition, the present invention relates to diagnostic and pharmaceutical compositions and the use of the molecule or the nucleic acid molecule of the invention in the treatment of acute myeloid leukaemia and/or myelodysplastic syndrome.