DIRAS3 mimetic peptide

The DIRAS3 mimetic peptide is a conformationally constrained cyclic peptide designed to replicate the tumor-suppressive functions of DIRAS3 (also known as ARHI), an endogenous RAS inhibitor. By mimicking the sequence spanning the α5 and hypervariable regions of DIRAS3, the peptide directly interferes with the KRAS-KRAS interface, thereby disrupting KRAS nanoclustering and preventing the engagement of downstream effectors. This mechanism allows for the simultaneous suppression of both the MAPK and PI3K/AKT signaling pathways across a wide range of KRAS hotspot mutations, including G12X and the Q61X variants that are typically resistant to current tricomplex RAS inhibitors. Developed by researchers at the University of Texas MD Anderson Cancer Center, the peptide is being investigated as a broad-spectrum therapeutic for RAS-driven cancers, such as ovarian and pancreatic malignancies.

Other names

DIRAS3-derived peptideDIRAS-3-derived peptideDIRAS 3-derived peptide