RSPO2-based peptibody-drug conjugate

The RSPO2-based peptibody-drug conjugate (PDC) is a preclinical research compound designed to target cancers expressing the leucine-rich repeat-containing G-protein coupled receptors LGR4, LGR5, and LGR6. Developed by researchers at the University of Texas Health Science Center at Houston, the conjugate consists of a peptibody targeting moiety—comprising a human IgG1-Fc domain fused to a mutant RSPO2 furin domain—conjugated to a cytotoxic payload. The RSPO2 furin domain contains a double mutation (M68T/Q70R) that preserves high-affinity binding to LGR4/5/6 but abolishes its ability to interact with RNF43/ZNRF3, thereby preventing the potentiation of oncogenic Wnt/β-catenin signaling. The peptibody is site-specifically conjugated to either a pyrrolobenzodiazepine (PBD) dimer (SG3199) or a camptothecin analog (CPT2). In preclinical studies, these PDCs demonstrated potent, receptor-specific cytotoxicity in vitro and robust anti-tumor efficacy in vivo against colorectal cancer and high-risk neuroblastoma models.

Other names

R-spondin-based peptibody-drug conjugateRSPO2-based PDCRSPO-2-based PDCRSPO 2-based PDC