Discovery and Optimization of the First ATP Competitive Type-III c-MET Inhibitor.

Recent clinical reports have highlighted the need for wild-type (WT) and mutant dual inhibitors of c-MET kinase for the treatment of cancer. We report herein a novel chemical series of ATP competitive type-III inhibitors of WT and D1228V mutant c-MET. Using a combination of structure-based drug design and computational analyses, ligand was optimized to a highly selective chemical series with nanomolar activities in biochemical and cellular settings.

Spatial organization of the transcriptional regulatory network of Saccharomyces cerevisiae.

A transcriptional regulatory network (TRN) is a complex network composed of all of the regulatory interactions between transcription factors and the corresponding target genes. Recently, three-dimensional (3D) genomic studies have shown that the 3D structure of the genome may influence the regulation of gene transcription, which provides us with a novel perspective. In the present study, we constructed the TRN of the budding yeast Saccharomyces cerevisiae and placed it in the context of a 3D genome model.

(15-Crown-5-κO)[S-(E)-1,2-dichloro-vinyl thio-sulfato-κO]sodium.

In the title complex, [Na(C(2)HCl(2)O(3)S(2))(C(10)H(20)O(5))], there are two independent complex units in the asymmetric unit, one of which has a 55:45% disorder in the 15-crown-5 component. The coordination sphere about the Na atom in each complex unit comprises five bonds to O atoms of the crown ether [Na-O = 2.390 (7)-2.