RP03707

RP03707 is a highly potent and selective proteolysis-targeting chimera (PROTAC) designed to induce the degradation of the KRAS G12D mutant protein. Developed by Risen (Shanghai) Pharma Tech, it utilizes a cereblon (CRBN)-recruiting E3 ligase ligand to target KRAS G12D for ubiquitination and subsequent proteasomal degradation. In preclinical studies, RP03707 demonstrated sub-nanomolar potency (DC50) in degrading KRAS G12D, effectively suppressing downstream MAPK signaling and inhibiting cell proliferation in multiple KRAS G12D-mutant cancer cell lines, including pancreatic cancer models. It has shown prolonged pharmacodynamic effects and significant anti-tumor efficacy in mouse xenograft models following intravenous administration.