Through our drug development expertise in brain & CNS disorders, we have developed a unique medicinal chemistry platform to discover novel product candidates. The compounds we have discovered work through modulation of NMDA receptors to avoid caustic effects associated with over-activation or full inhibition.
NMDA receptors are critically important in normal brain and nervous system function and play a key role in regulating how neurons connect to each other. The activation and opening of NMDA receptors, in response to the binding of specific neurotransmitters including glutamate, triggers a cascade of events that results in synaptic plasticity. This activation may be a beneficial therapeutic approach to treating disorders of the brain and nervous system.
For decades, researchers have attempted to discover and develop compounds that target NMDA receptors. To date these research efforts have resulted in either pure agonists or antagonists of the NMDA receptor. Compounds that activate the receptor—agonists—can produce excitotoxicity and neuronal damage from over activation. Alternatively, compounds that fully shut off or inhibit the receptor—antagonists—inhibit the formation of long-term plasticity, the strengthening of nerve cell connections, and ultimately learning and memory formation. Antagonists such as ketamine and PCP have been known to have significant abuse potential and also often lead to serious side effects including psychosis-like and dissociative symptoms.
Aptinyx has a platform for discovery of novel compounds that work through a unique mechanism to modulate—rather than block or over-activate—NMDA receptors and enhance synaptic plasticity. Our compounds bind at a unique domain on the NMDA receptor distinct from other existing drugs. We believe this binding and approach results in optimal modulation of the NMDA receptors while providing a favorable safety and tolerability profile.