Using the Center’s therapeutic development resources, NCATS scientists will collaborate 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.
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.
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 will provide 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 also 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, will identify and optimize new drug candidates for opioid misuse and addiction and for pain. 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.
In addition to NCATS resources, the National Institute of Neurological Disorders and Stroke (NINDS) has published a funding opportunity announcement on “Optimization of Non-Addictive Therapies to Treat Pain (UG3/UH3 Clinical Trials Not Allowed).” The goal is to speed the preclinical translational development necessary to advance small molecules and biologics to clinical testing for treatment of pain.