RLAA-KRASpep-2-GGG-R7

RLAA-KRASpep-2-GGG-R7 is an experimental peptide-based proteolysis-targeting chimera (PROTAC) designed to selectively target and degrade mutant KRAS proteins, specifically the G12D and Q61H variants. The molecule is composed of four functional modules: a cyclic peptide binder (KRASpep-2) that selectively recognizes mutant KRAS, a GGG linker, a polyarginine cell-penetrating peptide (R7) to facilitate intracellular delivery, and an RLAA motif that acts as a ligand for an E3 ubiquitin ligase. Developed by researchers at Kyungpook National University, RLAA-KRASpep-2-GGG-R7 has demonstrated the ability to reduce KRAS G12D protein levels and inhibit downstream AKT phosphorylation in AsPC-1 pancreatic cancer cells. This targeted protein degradation approach aims to overcome the challenges of 'undruggable' KRAS mutations in pancreatic, colorectal, and lung cancers.