CSF1R-IN-1

CSF1R-IN-1 is a small molecule inhibitor originally identified as a potent antagonist of the Colony stimulating factor 1 receptor (CSF1R). However, recent structure-based screening research presented at AACR 2024 identified it as a potential inhibitor of the Receptor tyrosine kinase-like orphan receptor 1 (ROR1). ROR1 is an orphan tyrosine kinase-like receptor that is exclusively expressed in various human malignancies, including pancreatic cancer, while remaining absent in normal adult tissues. In preclinical studies, CSF1R-IN-1 demonstrated significant antiproliferative activity in MiaPaCa-2 pancreatic cancer cells (IC50: 1.29 μM) by interacting with the ROR1 binding pocket through hydrogen bonding with ILE555 and ASP633, as well as pi-pi stacking with PHE552. Its efficacy appears to be cell-line dependent, as it showed minimal activity in PANC-1 cells.