Vision for ASPIRE

With the A Specialized Platform for Innovative Research Exploration (ASPIRE) initiative, NCATS seeks to accelerate preclinical drug discovery by integrating automated synthetic chemistry, high-throughput biology and information technologies to help scientists study unexplored biologically active chemical space.

The overall goal of ASPIRE is to enable 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:


ASPIRE’s biology component aims to establish a biological activity profile library of molecules in near real time to enable the identification of 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 confirming biological activities in human induced Pluripotent Stem Cells (hiPSC)-derived 3D printed tissues or organoids as necessary for molecular scaffolds of interest. A key goal of the biology component is the rapid turnaround of test data and biological annotations.

The ASPIRE biology platform will integrate existing high-throughput screening and lead optimization automation at NCATS with emerging state-of-the-art bioanalytical technologies to enable comprehensive “pharmacological intelligence” on molecular libraries.

Additionally, the ASPIRE biology platform will entertain new synthetic biology collaborations to generate molecular diversity, cell and macromolecular reagents to enable screening, and lead optimization in real time.


The chemical synthesis component of ASPIRE will focus on the development of 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 facilitate the entire synthesis workflow, from design to biological evaluation, with minimal human intervention through the adoption of strategic protocol standardization parameters. The goal is to implement innovative technologies that accelerate researchers’ ability to advance chemical synthesis automatically and to allow researchers to focus entirely on higher order intellectual activities that lead to meaningful discoveries and hypothesis generation.


Informatics research in ASPIRE is focused on the creation of 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, 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.


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 willing to collaborate.

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

Open Opportunities:

The Funding Opportunity Announcements below aim to promote partnerships between NCATS intramural investigators (i.e., those conducting research within the laboratories and clinics of NCATS) and extramural investigators (i.e., those conducting research in laboratories and clinics outside NIH).

  • RFA-TR-21-001 – New Chemistries for Un-drugged Targets through A Specialized Platform for Innovative Research Exploration (ASPIRE) Collaborative Research Program (UG3/UH3 Clinical Trials Not Allowed)
  • RFA-TR-21-002 – Virtual Approaches Towards New Chemistries for Un-drugged Targets through A Specialized Platform for Innovative Research Exploration (ASPIRE) Collaborative Research Program (U18 Clinical Trials Not Allowed)


Some publications may require a subscription to access full manuscripts.

Sittampalam, G. S.; Rudnicki, D. D.; Tagle, D. A.; Simeonov, A.; Austin, C. P. Mapping biologically active chemical space to accelerate drug discovery. Nature Reviews Drug Discovery 2019, 18 (2), 83 84.

Godfrey, A. G.; Michael, S. G.; Sittampalam, G. S.; Zahoránszky-Köhalmi, G. A perspective on innovating the chemistry lab bench. Frontiers in Robotics and AI 2020, 7, 24.

Zahoranszky-Kohalmi, G.; Siramshetty, V. B.; Kumar, P.; et al. A workflow of integrated resources to catalyze network pharmacology driven COVID-19 research. bioRxiv 2020, Preprint.

Zahoranszky-Kohalmi, G.; Wan, K. K.; Godfrey, A. G. Hilbert-curve assisted structure embedding method. ChemRxiv 2020, Preprint.