NeurOp’s technology to optimize selective and context-dependent NMDA inhibitors has led to the discovery of several proprietary compounds. Screening for drug-like properties among this group of compounds led to the identification of NP10679.

Properties of NP10679

  • NP10679 is selective for a specific NMDA subtype, GluN2B, and has increased potency in acidic conditions.
    • Over 100-fold more potent at GluN2B-containing NMDA receptors than other subtypes
    • 6-fold greater potency in lower pH (acidic) environments, a context relevant to a number of CNS disorders
  • Excellent drug-like properties, such as brain penetrance, half-life, oral bioavailability and weak CYP inhibition.
  • Effective in animal models of stroke, subarachnoid hemorrhage (SAH), perioperative pain (preliminary data) and opiate relapse (preliminary data)
  • Phase 1 clinical studies indicate excellent pharmacokinetics in humans
  • Phase 1 studies also suggest good safety margins for a number of possible indications such as stroke, SAH and acute severe pain

Phase 1 studies of NP10679 have been completed, and FDA approval of Phase 2 trial design is currently being sought.

Context-dependent NMDA receptor inhibition during subarachnoid hemorrhage

NP10679 illustration

A. An illustration of a subarachnoid hemorrhage with pooling of blood. A stylized vasospasm is expanded below, showing vasculopathy associated with luminal narrowing.

B. The left portion of the panel illustrates reduced pH (light maroon shading) in an ischemic zone around a vasospasm associated with the accumulation of extracellular glutamate (maroon spheres). The neuron on the left is undergoing excitotoxic cell death due to overactivation of NMDA receptors by glutamate (light magenta). The neuron on the right remains healthy under normal pH, with normal neurotransmission.

C. Similar neurons are shown in a patient receiving NP10679 treatment, in which NP10679 (cyan) selectively blocks NMDA receptor activation in areas of low pH (light maroon); NP10679 at normal pH (dark blue spheres) is without effect on normal neurotransmission. The pH sensitivity of NP10679, therefore, allows selective block of excessive NMDA receptor activation in the acidic ischemic zone without block of normal neurotransmission in unaffected tissue at normal pH.

Haichen Wang, Raymond J Dingledine, Scott J Myers, Stephen F Traynelis, Chuan Fang, Yanli Tan, George W Koszalka, Daniel T Laskowitz (2025) Clinical development of the GluN2B-selective NMDA receptor inhibitor NP10679 for the treatment of neurologic deficit after subarachnoid hemorrhage. J Pharmacol Exp Ther 392(1):100046.