Inositol glycans (IG's) are involved in numerous cellular signaling pathways, important in glucose metabolism, cell proliferation, immune responses, and steroidogenesis. Therapeutic agents designed to modulate IG-related signaling events may therefore lead to new treatments for diabetes, polycystic ovary syndrome, cancer, autoimmune, and other diseases. The objective of this new Insmed program is to create a library of novel compounds based upon key IG molecular features aimed at identifying new drug leads. In addition, the compounds will encompass a broad range of pharmacokinetic properties. In Phase 1 of this program we will synthesize a library, demonstrating our ability to establish molecular diversity around an IG-analog. Two main types of diversity-forming reactions - amine acylation and thiol addition - will be optimized using solid-phase parallel synthesis. The library will be tested in established whole-cell metabolic assays. This will set the stage for construction of expanded libraries in Phase 2 of this program.
The need for more specific therapeutic agents against metabolic diseases, autoimmune diseases and cancer is immense. IG's constitute rational approach toward such agents. This is the first parallel synthesis approach to IG analogs. The library will be used by Insmed for internal discovery efforts and for licensing to other pharmaceutical interests with complimentary expertise.
