The ChemAIRS platform successfully reconstructed a 25-step synthetic route to Revolution Medicines' groundbreaking KRAS inhibitor, elironrasib (RMC-6291). This next-generation therapeutic leverages a sanglifehrin-inspired macrocycle to form a stable tri-complex with KRAS-G12C(ON) and cyclophilin A (CypA), achieving exceptional selectivity through conformational rigidity.

Key ChemAIRS contributions:

• Modular retrosynthesis: Deconstructed the macrocycle into two manageable fragments

• Supply chain optimization: Identified commercially available starting materials

• Risk mitigation: Flagged potential side reactions for synthetic planning

• Route validation: Closely mirrored Revolution Medicines' published strategy

By combining macrocyclic drug design with AI-driven synthesis planning, ChemAIRS demonstrates how computational tools can accelerate the development of complex targeted therapies.