Drug discovery efforts related to small molecules are driven in the early stage by the Design-Make-Test-Analyze (DMTA) cycle. DMTA is a hypothesis-based research process where a compound is designed, synthesized, tested and analyzed, generating new findings and meaningful information at every stage of the cycle and informing the next iteration of the cycle, until a meaningful outcome for the project is achieved.
Accelerating the DMTA Cycle in Drug Discovery
The conventional DMTA cycle that is a core part of the drug discovery process is impacted by multiple factors including:
Manual workflows with long cycle times especially for the synthesis phase
The need for constant communications in real time between diverse teams and locations
Complex data generation and tracking
High upfront costs of discovery campaigns
The Solution: Automating the DMTA Cycle
To demonstrate the improved efficiencies of an automated DMTA cycle, Strateos virtually and physically integrated chemical and biological experimental components of the drug discovery process to enable researchers to select structures that can be prepared on automated systems and made available for follow-up biological testing, allowing for timely hypothesis testing and validation.
The goal was to illustrate the current processes for ‘closed loop’ drug discovery or lead optimization by synthesizing 14 structural analogs of the selected model compound, tofacitinib, purifying the analogs, and testing them in kinase inhibition assays (JAK1/2/3, TYK2).
This demonstration was performed at Strateos’ San Diego facility. Strateos operates multiple facilities which collectively span 14K sq. ft. with >200 instruments and 25 automation modules to enable more rapid optimization of reaction conditions for the synthesis of chemical compounds and support a range of the most common single-step reactions used in discovery synthetic MedChem, such as Buchwald, amide and Suzuki reactions. Additionally, software (API) integration with other digital tools, such as third party ELNs and LIMS, enable scientists to execute their workflows in the Strateos platform using their existing informatics landscape. After purification and structural verification, the target compounds can be assayed in the same smart lab facilities for functional testing such as inhibition assays, accelerating the DMTA cycle.
The Strateos Cloud Lab Platform enables the orchestration of scientific workflows virtually and the interactive command and control of our unique fleet of lab automation modules which can be accessed from anywhere in the world, speeding the Design-Make-Test-Analyze cycle and generating accurate, machine-actionable data.
By automating the DMTA cycle, scientists were able to work on multiple programs at the same time in parallel, greatly improving process efficiencies and shortening cycle times significantly.
DMTA Cycle Demonstration Results:
14 analog compounds and tofacitinib were designed, made, and assayed by the Strateos Cloud Lab in slightly less than ~40 hours over 4 days, 70% faster than the 2 weeks that a conventional CRO would require for such a project.
Key takeaways from this demonstration of a highly automated DMTA cycle include:
DMTA cycle time is significantly reduced, leading to faster discovery and faster go-to-market
Process control, supervision, monitoring and data capture was accomplished with the Strateos Lab Control Software platform
Centralized automated data capture provides accuracy, end-to-end traceability, reproducibility and precision
Scalable and automated workflows offered by Strateos’ unique fleet of lab automation modules can be a vital asset for small and large drug discovery campaigns
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