Sanford Burnham Prebys Medical Discovery Institute has received a USD 3.86 million UG3 cooperative agreement from the National Institute of Neurological Disorders and Stroke to advance a non-opioid small molecule program targeting the neurotensin receptor 1 (NTR1) for pain management. The award, issued under the NIH HEAL Initiative funding opportunity RFA-NS-24-019, covers the period from April 2026 through March 2028 and lists Lauren M. Slosky, Steven H. Olson, and Ru-Rong Ji as principal investigators.
The program centers on SBI-553, a beta-arrestin 2-biased allosteric modulator of NTR1 that binds at an intracellular site and selectively directs receptor signaling toward the beta-arrestin 2 pathway rather than G protein activation. Preclinical data in rodent models showed the compound reduced hypersensitivity in postoperative and neuropathic pain settings and suppressed excitatory synaptic transmission in spinal cord nociceptive neurons, with activity also observed in human nociceptive sensory neurons in vitro. The UG3 phase will use structure-based drug design and AI-assisted computational methods alongside cryo-EM co-structure determination to drive lead optimization from SBI-553 analogs toward a clinical candidate.
The UG3 mechanism is milestone-contingent, with a prospective UH3 phase intended to complete IND-enabling studies and initiate a Phase I single ascending dose study in healthy volunteers, though transition to that stage remains dependent on meeting predefined criteria.
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