Automated, miniaturized and accelerated drug discovery: AMADEUS

Descripción del proyecto

Descubrimiento de fármacos con automatización

La química sintética, a diferencia de muchos otros campos, ha tardado en adoptar la automatización y la miniaturización. El proceso de descubrimiento de fármacos actual requiere mucho tiempo, es costoso y a menudo ineficaz, ya que depende en gran medida de procedimientos manuales. Además, el impacto ambiental y los problemas de reproducibilidad de los métodos de síntesis tradicionales siguen siendo retos importantes. A pesar de estos obstáculos, la automatización podría acelerar los descubrimientos, reducir los costes y mejorar la seguridad y la sostenibilidad. El equipo del proyecto AMADEUS, financiado por el Consejo Europeo de Investigación, pretende revolucionar este espacio. Ofrece una plataforma totalmente autónoma capaz de sintetizar miles de moléculas pequeñas al día en volúmenes de nano o picolitros. Mediante la integración de módulos de síntesis, purificación y optimización basada en el aprendizaje automático, en AMADEUS se acelera el descubrimiento de fármacos al tiempo que se reducen los costes y se democratiza el acceso a nuevos tratamientos.

Objetivo

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.