SILC – S100A9 Inhibition by Low molecular weight Compounds - is a preclinical immuno-oncology project aimed at identifing small molecules that target the S100A9 protein and inhibit its interaction with pro-inflammatory receptors on immune cells in the tumor microenvironment.
S100A9 is expressed in the tumor microenvironment and has been implicated in the development of cancer by recruiting and activating specific immune cells, e.g. myeloid-derived suppressor cells (MDSCs). The MDSCs are of major importance in the development of cancer. They contribute to the formation of blood vessels in the tumor (angiogenesis), in the creation of an immunosuppressive tumor microenvironment that enables cancer cells to elude attacks by the immune system and by promoting establishment of metastasis. Small molecules blocking the function of S100A9 provide a new approach to help the body’s immune system to fight cancer as a single therapy or in combination with other immunotherapies.
Figure 1. S100A9 promotes tumor progression. Illustration adapted from Riehl et al., Cell Communic Signal, 2009.
High-throughput screening (HTS) has been performed in collaboration with Evotec AG to identify novel small molecules that bind S100A9 and inhibit its interaction with receptor of advanced glycation end product (RAGE) and Toll-like receptor 4 (TLR4). Further screening and subsequent optimization has generated lead S100A9-inhibiting compounds with suitable pharmacokinetic properties for oral administration. International patent-applications have been filed for three structurally different compound classes. One of these patent applications is granted by the European Patent Office.
SILC is a first-in-class opportunity focused on treatment of cancer. There is, however, a number of alternative diseases also suitable for S100A9 targeting, e.g. Alzheimer’s disease and osteoarthrithis.
Commercial activities aimed at out-licensing the SILC project are ongoing.