Accelerating the Translation of Novel Compounds Toward INDs for Subsequent Clinical Testing

Using the Center’s therapeutic development resources, NCATS scientists are collaborating with the external research and development community, as well as with other scientists at NIH, to identify and test existing and potential new drugs for preclinical development. The following three initiatives are focused on facilitating the testing needed to bring promising drug candidates to first-in-human studies.

NCATS-led Preclinical NIH HEAL Initiative. Human Cell-Based Screening Platforms and Novel Drugs to Treat Pain, Addiction, and Overdose. A diagram showing NCATS’s plans to make human cell-based platforms available as models to test new treatments for pain, addiction, and overdose. Labeled “Accelerating Translation of Novel Compounds to Investigational New Drugs for Subsequent Clinical Testing,” the diagram shows the continuum of preclinical development, from early to late, and clinical testing and trials, illustrating NCATS’s efforts to partner with researchers to accelerate the development of promising compounds into new drugs to address pain, addiction, and overdose. This proecess begins with development of new chemical structures to modulate novel targets and alter a cell’s pain and reward pathways; followed by development of pharmacological probes for novel targets, identifying promising chemical structures and developing them into pharmacological or drug-like compounds; and finally followed by development of investigational drugs ready for clinical testing that will evaluate these potential drugs for safety and effectiveness in preparation for regulatory approval and clinical trials and testing in humans.

Developing New Chemical Structures to Modulate Targets of Pain, Addiction and Overdose

Through this initiative, researchers will design and build new chemistries, biological assays, data-mining tools and other analysis technologies directed toward altering a cell’s pain and reward pathways. NCATS is asking the research community for concepts to design novel chemicals that have the potential to address pain, addiction and overdose. Promising ideas for the new chemical structures will be carried forward and tested through NCATS’ A Specialized Platform for Innovative Research Exploration (ASPIRE), an automated synthetic chemistry (ASC) modular platform. Using this platform, scientists will apply new ASC techniques and testing capabilities to accelerate the development of new therapeutics.

ASPIRE Challenges

NCATS has issued challenge prize competitions for an innovative translational science platform resulting from the integration of various components, such as design of a chemistry database, an electronic laboratory knowledge portal, machine learning algorithms, and biological assays focused on the areas of pain, addiction and overdose. The goal is to revolutionize the discovery of novel compounds for the treatment of pain, opioid use disorder and overdose. The Center anticipates that this integrated platform ultimately can be generalized to address many of the roadblocks in automated chemistry. 

Creating Pharmacological Probes for Novel Targets

Research experts in pain and opioid misuse and addiction have identified compounds that act on biological targets of opioids and pain and tested them in cell- and animal-based models. NCATS is providing access to resources and expertise to advance the preclinical development of these compounds and further develop them into drug-like compounds to position them for eventual testing in humans. Available collaborative resources include compound libraries, high-throughput screening, test validation, informatics tools and medicinal chemistry. The libraries will leverage repositories of natural products available through the National Cancer Institute and the Fogarty International Center.

Developing Investigational Drugs Ready for Clinical Testing

Scientists working with NCATS’ Preclinical Therapeutic Development Branch, including those in the Therapeutics for Rare and Neglected Diseases and Bridging Interventional Development Gaps programs, are identifing and optimizing new drug candidates for opioid misuse and addiction and for pain and opioid use disorder. Researchers will determine which candidates can be further developed and tested to enable IND applications to the FDA and subsequent early-phase testing in humans. Available resources include medicinal chemistry, pharmacology, testing of the metabolic properties of compounds, compound safety profiles, optimal drug formulation for administration in humans, and manufacturing methods to produce sufficient quantities of potential drugs for preclinical and clinical evaluation.