Emerging RAS Inhibitors: Heterocyclic and Spirocyclic Compounds in Cancer Therapeutics

Abstract

Researchers have long recognized RAS mutations as one of the most challenging targets in oncology. These genetic alterations are central drivers of tumor progression in cancers such as melanoma, colorectal cancer, and pancreatic adenocarcinoma. The recent advancements described in patent applications WO 2024/243186 A2 and WO 2024/246099 A1 introduce two novel classes of inhibitors: heterocyclic compounds targeting NRAS G12D and spirocyclic derivatives directed at KRAS mutations, including G12C, G12D, and G12 V. These compounds, a fresh and innovative approach, disrupt critical RAS-dependent signaling pathways, offering a pathway to mitigate tumor growth and overcome resistance to standard therapies. This Patent Highlight explores their mechanisms, preclinical successes, and implications for future cancer treatment strategies.