Flat SAR of P3-methylsulphonamide based small molecule legumain inhibitors

This letter describes the design, development and SAR exploration of a novel series of small legumain inhibitors. The SAR of a new small molecule legumain inhibitor chemotype was explored and found to have improved physiochemical properties compared to previously developed inhibitors within our group. However, further development of this series was found to be limited as the SAR was observed to be relatively flat.

A gene-signature progression approach to identifying candidate small-molecule cancer therapeutics with connectivity mapping

Gene expression connectivity mapping has gained much popularity recently with a number of successful applications in biomedical research testifying its utility and promise. Previously methodological research in connectivity mapping mainly focused on two of the key components in the framework, namely, the reference gene expression profiles and the connectivity mapping algorithms. The other key component in this framework, the query gene signature, has been left to users to construct without much consensus on how this should be done, albeit it has been an issue most relevant to end users. As a key input to the connectivity mapping process, gene signature is crucially important in returning biologically meaningful and relevant results. This paper intends to formulate a standardized procedure for constructing high quality gene signatures from a user’s perspective.