Progress and challenges in the design and development of selective KRAS G12D-targeted drug discovery: inhibitors, degraders and emerging therapeutic strategies.

Abstract excerpt

KRAS is one of the most frequently mutated oncogenes in human cancers, with KRAS G12D representing the predominant mutation in pancreatic ductal adenocarcinoma and a major driver of colorectal and lung cancers. Although KRAS was long considered "undruggable" due to structural and biochemical constraints, the discovery of the switch-II pocket enabled the development of direct KRAS inhibitors, leading to the...

Topics

• Humans
• Antineoplastic Agents
• Proto-Oncogene Proteins p21(ras)
• Drug Discovery
• Drug Design
• Proteolysis Targeting Chimera