ChemAIRS is revolutionizing radiotheranostic drug discovery by providing AI-powered retrosynthetic planning for complex radioligands. As PSMA-targeted therapies like Pluvicto™ prove transformative in prostate cancer, overcoming resistance and heterogeneity requires next-generation targets like NTSR1—and scalable synthesis to match.

By combining domain expertise with advanced retrosynthetic algorithms, ChemAIRS accelerates the design of efficient, cost-effective routes for critical precursors. This empowers researchers to rapidly innovate against PSMA-refractory disease and beyond, shortening the path to life-saving radiopharmaceuticals for advanced cancers

Macrocyclic inhibitors targeting the 3C-like protease hold immense promise in combating coronaviruses like SARS-CoV-2—yet their intricate synthesis poses a major hurdle. In this case study, we explore how ChemAIRS, an AI-driven retrosynthesis platform, revolutionizes the process by identifying scalable synthetic routes. Demonstrating its capabilities, ChemAIRS successfully mapped efficient pathways for two macrocyclic compounds from Vir Biotechnology’s patent. By integrating domain expertise with advanced cheminformatics, ChemAIRS accelerates route scouting, overcomes synthetic barriers, and drives innovation in drug discovery—proving itself as an indispensable tool for modern medicinal chemistry

Utilizing the AI-powered retrosynthetic platform ChemAIRS, multiple synthetic routes to the selective OX2R agonist ALKS 2680 were computationally generated and evaluated. The following sections summarize three distinct synthetic strategies:

1. The published route disclosed by Alkermes

2. A de novo discovery route enabled by ChemAIRS

3. A scalable synthetic sequence also proposed by ChemAIRS with an emphasis on practicality and supply chain readiness

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.

ChemAIRS transformed retrosynthesis planning for Novo Nordisk’s diboron-based glucose-sensitive derivatives—delivering unprecedented efficiency gains and scalable routes. By integrating microwave-assisted Ir-catalyzed C–H borylation and ultra-low Pd Miyaura couplings (B₂(neop)₂/B₂Pin₂ optimization), ChemAIRS achieved what traditional methods couldn’t: compressing a 12-day synthesis into 1 hour while reducing Pd loading 100-fold. Our retrosynthetic strategy identified optimal disconnections, minimized competing pathways, and enabled cost-effective scale-up of these critical glucose-responsive therapeutics. See how intelligent route design and catalytic innovation are redefining medicinal chemistry timelines.

ChemAIRS optimized synthesis of Schrödinger’s Phase 1 MALT1 inhibitor SGR-1505—proposing a novel Curtius rearrangement route and an early asymmetric methylation strategy to bypass expensive chiral purification. Revolutionize your complex molecule synthesis with AI-driven retrosynthesis.

ChemAIRS overcame the synthetic challenges of Arcus Biosciences’ HIF-2⍺ inhibitor AB521 (casdatifan)—a complex molecule with four rings and five stereocenters—by designing convergent routes and enabling parallel intermediate synthesis. Accelerate your anticancer drug development with AI-driven retrosynthesis

ChemAIRS accelerated Novartis’ WRN inhibitor (HRO761) development by designing a robust 13-step synthesis and patent-diverting alternatives that optimize intermediates and reduce side-reaction risks—empowering this first-in-class MSI-solid tumor therapy. Transform your oncology pipeline with AI-driven retrosynthesis

ChemAIRS accelerates development of groundbreaking CB2R inverse agonists (ETH/OHSU/Roche) by optimizing HU-308-derived syntheses—delivering high-affinity, CB1R-selective compounds with minimized CNS side effects. Discover how AI-driven retrosynthesis overcomes pitfalls in cannabinoid drug discovery.

ChemAIRS enabled efficient synthesis of Boehringer Ingelheim’s chiral spirocyclic isoxazolone—a versatile scaffold with anti-inflammatory to anticancer potential—by proposing multiple pathways, flexible starting materials, and scalable conditions while mitigating side reactions. Discover how AI-driven retrosynthesis accelerates heterocyclic drug development.

ChemAIRS redefined synthetic strategy for Takeda's αvβ1-targeting azabenzimidazolone antifibrotic, proposing novel routes that bypass traditional limitations. By anticipating side reactions and optimizing pathways, our AI-driven platform delivers reliable, innovative solutions for complex drug discovery challenges.

ChemAIRS analyzed Vertex's OX2R-targeting macrocyclic amines (like compound 29), proposing API synthesis routes that match published methods while suggesting novel alternatives. This AI-driven flexibility accelerates CNS drug discovery by empowering chemists to explore optimized pathways for high-affinity, brain-penetrant therapeutics.

ChemAIRS, our AI-driven retrosynthesis platform, accelerated Merck's breakthrough KRAS G12C inhibitor discovery by proposing efficient synthetic routes and mitigating risks. By aligning with proven methods while offering optimized pathways, ChemAIRS empowers safer, faster drug development for innovative cancer therapies.

ChemAIRS, our AI-driven retrosynthesis platform, predicted Janssen’s synthetic route for a potent RSV fusion inhibitor—targeting a virus that hospitalizes vulnerable populations—and proposed a cost-effective alternative. This demonstrates ChemAIRS’ ability to generate optimized, customizable pathways for efficient drug synthesis.

ChemAIRS delivers AI-powered retrosynthesis for PRMT5 inhibitors—key epigenetic cancer targets—generating efficient, novel routes aligned with Gilead Sciences' research. Accelerate your drug discovery with reliable, unreported synthetic strategies for next-generation therapies

"ChemAIRS rapidly generated unreported synthetic routes for Genentech & Convelo’s brain-penetrant EBP inhibitor—a breakthrough remyelination therapy—delivering cost-efficient pathways in minutes. Transform your CNS drug discovery with AI-driven retrosynthesis.

ChemAIRS optimized Kymera/Sanofi’s Phase 2 IRAK4 degrader KT-474—proposing scalable synthetic strategies that enhance efficiency, prevent side reactions, and streamline scale-up. Transform your targeted protein degrader development with AI-driven retrosynthesis

ChemAIRS accelerated the development of Milvexian—BMS/Janssen’s breakthrough oral FXIa inhibitor—by designing scalable synthetic routes for its key triazole intermediate while predicting impurities and optimizing scale-up. Transform your anticoagulant drug development with AI-driven retrosynthesis.

ChemAIRS demonstrated its synthetic versatility by designing multiple routes to Bayer’s M₂ PAM BAY 2413555—a heart failure candidate—identifying key disconnections, optimizing intermediates, and providing scalable conditions. While preclinical vascular inflammation halted development, our AI-driven platform continues to accelerate cardiovascular drug discovery with precision.

ChemAIRS optimized synthetic routes for GSK’s novel αvβ6 integrin inhibitors—key targets in TGF-β1-driven fibrosis—enhancing scalability, selectivity, and yield while reducing side reactions. These orally bioavailable candidates (including leads (S)-20 and 28) show promise for treating idiopathic pulmonary fibrosis, demonstrating AI’s power in accelerating antifibrotic drug development.