KAN0441571C

KAN0441571C is a second-generation, small molecule inhibitor that selectively targets receptor tyrosine kinase orphan receptor 1 (ROR1). ROR1 is an oncofetal protein absent in most normal adult tissues but overexpressed in various malignancies, and it is implicated in tumor cell survival, proliferation, and metastasis. KAN0441571C effectively induces apoptosis in malignant cells by dephosphorylating ROR1 and its associated signaling pathways, most notably the non-canonical WNT signaling pathway (PI3Kδ/AKT/mTOR). It demonstrates single-agent activity in inducing cell death in several cancer models, including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), small cell lung cancer (SCLC), and non-small cell lung cancer (NSCLC). Preclinical data show that KAN0441571C enhances apoptotic effects and has strong synergy in combination with other targeted agents, such as the BCL-2 inhibitor venetoclax, BTK inhibitor ibrutinib, EGFR inhibitor erlotinib, PI3Kδ inhibitor idelalisib, and mTOR inhibitor everolimus. The drug is being developed by Kancera.