Small Molecule · GATE-251

Zelquistinel (GATE-251)

Phase 2Syndeio Biosciences, Inc.
  • Fast Track

Oral, once-weekly third-generation NMDA-receptor positive allosteric modulator acting at a novel site independent of the glycine co-agonist site; enhances activity-dependent synaptic plasticity with rapid, sustained antidepressant-like effects. Originated at Naurex → Allergan (AGN-241751) → Gate Neurosciences / Syndeio Biosciences. Lead indication major depressive disorder.

Also known as: GATE-251, Zelquistinel, AGN-241751

Data current as of

Modality
Small molecule
Chemical class
diazaspiro[3.4]octane, carbamate
Chemistry
Single enantiomer
Mechanism
GluN2B PAM
Highest phase
Phase 2
Lead indication
Major depressive disorder
Developer
Syndeio Biosciences, Inc.
Designations
Fast Track
Trials
2 tracked · 2 recruiting · 66 sites

Mechanism of action

NMDA-receptor positive allosteric modulator at a novel site independent of the glycine co-agonist site; potentiates GluN2A- and GluN2B-containing receptors, with antidepressant-like effects dependent on GluN2B. Positively modulates (not blocks) the receptor — contrasting ketamine.

TargetActionAffinity
GluN2BprimaryGRIN2BPAM—ⓘ
GluN2AGRIN2APAM—ⓘ

Formulations

FormulationRouteRegimenPharmacokinetics
Zelquistinel oral tablet
6 mg oral tablet once weekly (Phase 2, NCT07115329); 3 mg and 10 mg once-weekly doses studied in the Phase 2a dose-finding study
OralOnce weeklyt½ 0.5 h

Development timeline

Phase 2Feb 2025 – Jan 2026
  1. Second Phase 2 MDD study NCT07115329 started.
  2. Phase 2 MDD study NCT06547489 started.

Zelquistinel (GATE-251) for Major depressive disorder

Phase 2RecruitingMajor depressive disorder indication →

Zelquistinel (GATE-251), oral once-weekly NMDAR PAM for MDD. Two recruiting Phase 2 MDD studies (NCT06547489, NCT07115329). FDA Fast Track designation (2018, as AGN-241751). Strategic shareholders include AbbVie and Eli Lilly.

Clinical trials

NCT07115329Phase 2Recruitingn=164

Phase 2 Study of Oral GATE-251 (Zelquistinel) for Major Depressive Disorder

Started Jan 2026· Primary completion Mar 2028· 📍 32 sites across 1 country (United States)

NCT06547489Phase 2Recruitingn=164

Phase 2 Study of Oral GATE-251 (Zelquistinel) for Major Depressive Disorder

Started Feb 2025· Primary completion Sept 2027· 📍 34 sites across 1 country (United States)

Related compounds

Other GluN2B compounds

More from Syndeio Biosciences, Inc.

Identifiers

Sources

  1. A Phase 2 Study of Zelquistinel or Placebo for the Reduction of Symptoms of Major Depressive Disorder (NCT07115329) — ClinicalTrials.gov
  2. Zelquistinel Is an Orally Bioavailable Novel NMDA Receptor Allosteric Modulator That Exhibits Rapid and Sustained Antidepressant-Like Effects — Int J Neuropsychopharmacology
  3. Zelquistinel or Placebo for the Reduction of Symptoms of Major Depressive Disorder (NCT06547489) — ClinicalTrials.gov
  4. Zelquistinel Phase 2 MDD (NCT07115329) — ClinicalTrials.gov