SHY-855

SHY-855 is a novel, non-covalent small-molecule inhibitor designed to target the orthosteric GTP-binding pocket of K-Ras and other members of the Ras superfamily of small GTPases. Developed by researchers at the University of Illinois Chicago, SHY-855 functions as a pan-Ras inhibitor by competing directly with GTP binding, a mechanism previously considered difficult to achieve due to the extremely high affinity of Ras proteins for GTP. The compound has demonstrated the ability to inhibit downstream signaling and cellular proliferation in human pancreatic and non-small cell lung cancer (NSCLC) cell lines expressing both wild-type and mutant K-Ras (including G12D, G12V, and G13D). Its activity extends to other superfamily members such as RAB5A and RAB35, suggesting potential therapeutic utility across a broad range of GTPase-driven malignancies.