Automated, miniaturized and accelerated drug discovery: AMADEUS

ongoing

The mantra ‘Automation + Miniaturization = Acceleration’ is successfully applied in many research areas and technologies, but not in synthetic chemistry, which is largely believed to be not automatable. However, with the potential to accelerate discoveries while flattening costs, increase safety, streamline data generation, enhance reproducibility, and lower the environmental footprint, automation and miniaturization are two promising approaches to synthesis and are worthwhile to invest in. I will engineer and validate a comprehensive, technology platform, AMADEUS (Automated, MiniAturizeD, and acceleratEd drUg diScovery), which is able to synthesize in a fully autonomous manner thousands of small molecules per day in nano- or picolitre volumes, based on hundreds of chemistries, efficiently screened and optimized for properties using artificial intelligence. The AMADEUS process will be achieved by interfacing four different modules: a synthetic part based on acoustic droplet ejection technology, coupled with a UPLC MS QC and purification module, and a flexible mounted screening unit. A machine learning module will retrieve and process all relevant synthesis, QC, and screening ‘real-time’ data and automatically guide the iterative optimization cycle. AMADEUS will be showcased with several medicinal chemistry, catalysis, and organic chemistry projects. With my project, I want to challenge the early drug discovery process, which for over 50 years in pharma companies around the world has (almost uniformly) been pursued and comprises two blocks, 1) a high throughput screen relying on millions of curated and stored compounds and 2) the subsequent hit-to-lead optimization phase often called the ‘design, make, test cycle’. AMADEUS will contribute to the accelerated discovery of drugs for unmet medical needs and ultimately reduce drug costs for patients. AMADEUS is a highly sustainable synthesis platform. AMADEUS will help democratize drug discovery.