ASPIRE Laboratory

Medicinal chemistry equipment in the lab at NCATS. (Daniel Soñé Photography)

The overall goal of ASPIRE is to allow real-time translational science by combining expertise in chemistry, biology, pharmacology, automation and AI/ML to provide a rapid decision-making platform to advance lead molecules to the clinic.

More information about the capabilities of the intramural laboratory will be added in the coming months.

Learn more about ASPIRE capabilities in the following areas.

Biology

The goal of ASPIRE’s biology component is to form a biological activity profile library of molecules in near real time to identify novel, next-generation molecules with drug-like properties. Early profiling will include solubility, biochemical and cellular activity using pharmacologically relevant assay reagents and assay platforms. Additional testing will include target engagement, biophysical properties, in vitro PK/PD/toxicology and proven biological activities in human-induced pluripotent stem cell (hiPSC)–derived 3D printed tissues or organoids as necessary for molecular scaffolds of interest. A key goal of the biology component is the quick turnaround of test data and biological annotations.

Chemistry

The chemical synthesis component of ASPIRE will focus on developing core expertise and technologies involved in reaction screening, which automatically will be translated directly into successful reaction batch production of synthetic targets. A key aim is to push the entire synthesis workflow from design to biological evaluation, with minimal human intervention, through use of strategic protocol standardization parameters. The goal is to begin innovative technologies that speed up researchers’ ability to advance chemical synthesis automatically and to allow researchers to focus entirely on higher-order intellectual activities that lead to key discoveries and hypothesis generation.

Informatics

Informatics research in ASPIRE is focused on creating a “chemical intelligence” powered integrated computational platform to drive the autonomous design and synthesis of novel therapeutics and the exploration of unknown chemical space and knowledge. To accomplish this goal, the ASPIRE initiative is building a high-quality reaction knowledgebase via the integration of historical and high-throughput synthesis data. With the help of AI/ML methods — including network analysis, traditional machine learning and deep learning techniques — ASPIRE aims to develop novel computational methods for the design and synthesis of novel bioactive molecules of therapeutic potential. The methods will form an automated computational pipeline addressing molecular modeling, retrosynthesis planning, reaction execution, and optimization of reaction conditions and the properties of the target molecules.

ASPIRE prioritizes the early dissemination of novel reaction informatics methods and potentially public data sets. In the future, ASPIRE will host a collection of source code repositories and computational tools for both NCATS and extramural researchers to use.

Collaboration

Collaborations are critical to the successful implementation of ASPIRE at NCATS. The project intends to develop and share tools, technologies and standardized protocols in automation, chemistry, biology, pharmacology and informatics — both internally and in partnership with extramural researchers. These assets will be openly shared with appropriate protections for intellectual property rights for registered institutions that are willing to share their research.

Partnerships can be managed with Confidentiality Agreements (CDA), Research Collaboration Agreements (RCA) and other instruments compatible with individual research institutions.

Automation

One of the aspects of automation that is most appreciated, particularly in the life sciences, is its ability to relieve researchers of routine tasks that can be readily developed into well-orchestrated processes run by robots. In addition to allowing scientists more time and opportunity to pursue innovative activities, automation can lead to better reproducibility, which, in turn, leads to more rapid and convincing discoveries. NCATS has extensive experience in robotically executed biological assays and aims to use some of that expertise to improve its ability to synthesize molecules with minimal human involvement, which is a challenge when the goal is to integrate other key aspects of molecular synthesis as well, such as purification, characterization and plating for screening.

Infrastructure

NCATS has thought a lot about how to develop a proper infrastructure for ASPIRE. One key infrastructure objective is space, and NCATS recently secured the renovation of a 4,400 ft2 open laboratory space to house ASPIRE and supporting technologies. We are designing the space with an eye toward the flexibility, portability and evolution of technology solutions to keep pace with the rapidly changing scientific discovery and drug development landscape. Another key infrastructure objective involves developing hardware and software frameworks that can be used as work process standards, which will lead to lower costs in the development, operation and duplication of the technology elsewhere. NCATS’ ultimate goal is to promote the development of platforms similar to ASPIRE to improve transdisciplinary partnership and speed up the discovery of innovative and effective treatments.

View a list of select publications.

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