Semafore Pharmaceuticals, Inc.

Dysregulation of the phosphatidylinositol-3-kinase (PI3K) pathway in a wide range of tumors has made PI3K a consensus target to inhibit as illustrated by more than 15 inhibitors now in clinical trials. Our previous work, built on the early pioneering multikinase inhibitor LY294002, resulted in the only PI3K vascular-targeted PI3K inhibitor prodrug, SF1126, which has now completed Phase I clinical trials. This inhibitor has properties that impart more in vivo activity than should be warranted by its enzymatic potency, which in general is much lower than other clinical stage PI3K inhibitors. We embarked on the exploration of scaffolds that retained such properties while simultaneously exhibiting an increased potency toward PI3K. This work resulted in the discovery of the 5-morpholino-7H-thieno[3,2-b]pyran-7-one system as the foundation of a new compound class of potential PI3K inhibitors having improved potency toward PI3K. The synthesis and cancer stem cell-based activity of these compounds are reported herein.

In mid 2007 Molecular Diversity (MODI) underwent an editorial management transition with the implementation of a new Editor in Chief and a team of Associate Editors. With the support and guidance ofMODI’s Editorial Advisory Board and Springer, we began the process of rebuilding and modernizing MODI. We reviewed the progress, scope, infrastructure, current status of our journal, identified our weaknesses and deficiencies, and set a plan to address those issues to improve our journal. I would like to share with you the results of this review. Currently, MODI is abstracted/indexed in the following databases: