SSR128129E

SSR128129E is a small molecule, orally active, allosteric inhibitor of Fibroblast Growth Factor Receptor 1 (FGFR1). Developed by Sanofi, it is chemically distinct from traditional tyrosine kinase inhibitors as it binds to the extracellular domain of the receptor rather than the ATP-binding site, providing high selectivity for FGFR1. SSR128129E blocks FGF2-induced signaling, cell proliferation, and migration. In oncology research, it is being investigated for its ability to remodel the immunosuppressive tumor microenvironment. Specifically, in models of B-cell lymphoma, SSR128129E has been shown to inhibit FGFR1 activity in cancer-associated fibroblasts (CAFs), leading to a significant reduction in the transcription and secretion of TGFβ. This reduction in TGFβ levels helps to reverse microenvironmental immunosuppression, thereby enhancing the expansion, infiltration, and anti-tumor activity of CAR T-cell therapies, including CD19-CAR T and BAFFR-CAR T cells.