Abstract 384: IPS-06061, a novel TPD molecular glue degrader targeting KRAS G12D

Abstract We have discovered a novel KRAS G12D-degrading Molecular Glue using IPS's cutting-edge ProGlu AI-based drug discovery platform and PPIExplorer, an IPS-Chip based Proteomics technology. ProGlu accurately predicts PPI between E3 ligase and KRAS G12D through MD simulation, enabling de novo design of MG degraders. One such degrader, namely IPS-06061, was successfully synthesized and confirmed a strong anti-tumor efficacy using a xenograft animal model. These data demonstrate that KRAS MG will be a promising new therapeutic modality for the treatment of PDA, CRC, and NSCLC. Citation Format: Incheol Kang, Seungoh Seo, Seong Hyeok Cho. IPS-06061, a novel TPD molecular glue degrader targeting KRAS G12D [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 384.