NLGN1

Neuroligin-1

Score: 0.511 Price: $0.51 Medium Druggability Status: active Wiki: NLGN1

🧠 Neurodegeneration

HYPOTHESES

1

PAPERS

0

KG EDGES

12

DEBATES

1

3D Protein Structure

🧬 NLGN1 — PDB 3BIW Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.45

Clinical Stage

Phase II

Target Class

Receptor

Safety

0.40

Druggability Analysis

Drug Development0.40

Structural Tractability0.70

Target Class0.70

Safety Profile0.40

Key Metrics

PDB Structures:

7

Known Drugs:

4

Approved:

0

In Clinical Trials:

2

Drug Pipeline (4 compounds)

1 Preclinical

Druggability Rationale: This receptor has moderate druggability. Binding site accessibility or signaling complexity may require biologic or allosteric modulator approaches rather than conventional small molecules. Crystal structures available (7 PDB entries) supporting structure-based drug design. AlphaFold predicted structure available for computational screening.

Mechanism: Drugs targeting NLGN1 would modulate synaptic adhesion by either enhancing or blocking the neuroligin-neurexin interaction at the postsynaptic membrane, thereby regulating synapse formation, stabilization, and synaptic transmission. Indirect modulators may enhance GABAergic signaling or vasopressin-mediated pathways that influence neuroligin-dependent synaptic maturation and plasticity.

Drug Pipeline (4 compounds)

1 Preclinical

Known Drugs:

Balovaptan (phase2) — Autism Spectrum Disorder - synaptic adhesion modulation via vasopressin signaling

Arbaclofen (phase2) — Autism Spectrum Disorder - GABAergic signaling affecting synapse maturation

NLGN1-targeting nanobodies (preclinical) — Research compounds targeting neuroligin cell adhesion and synaptic plasticity

Alpha-neurexin modulators (research) — Preclinical tools modulating NLGN1-neurexin interaction at synapses

Structural Data:

PDB (7) ✓AlphaFold ✓Cryo-EM —

3B3Q 3BIW 3BIX 3VKF 5OJ6+2 more

UniProt: A0A1D5RMP7

🧬 3D Protein Structure

🧬 NLGN1 — PDB 3BIW Click to expand interactive 3D viewer

Experimental structure from RCSB PDB | Powered by Mol* | Rotate: click+drag | Zoom: scroll

Selectivity & Safety Considerations

Receptor subtype selectivity is essential for therapeutic efficacy and safety. Cross-reactivity with related receptors should be profiled early in drug discovery.

3D Protein Structure

PDB: Open in RCSB AlphaFold model

Interactive 3D viewer powered by RCSB PDB / Mol*. Use mouse to rotate, scroll to zoom.

Clinical Trials (8)

Relevant trials from ClinicalTrials.gov

Active

0

Completed

8

Total Enrollment

1,096

By Phase

NA: 1 · PHASE1: 3 · PHASE2: 2 · PHASE3: 2

A Study to Evaluate the Long-term Safety of Arbaclofen Extended-Release Tablets for Patients With Spasticity Due to MS Completed

PHASE3 NCT03319732 n=323

Multiple Sclerosis, Spasticity, Muscle

Interventions: Arbaclofen

Sponsor: RVL Pharmaceuticals, Inc. | Started: 2018-04-03

One Year, Open Label, Dose Escalation Long-term Safety Study in Multiple Sclerosis (MS) Subjects With Spasticity Completed

PHASE3 NCT01844232 n=150

Multiple Sclerosis, Spasticity

Interventions: arbaclofen

Sponsor: RVL Pharmaceuticals, Inc. | Started: 2013-04

Study To Evaluate The Efficacy And Safety Of Balovaptan In Adults With Post-Traumatic Stress Disorder (PTSD) Completed

PHASE2 NCT05401565 n=29

Stress Disorders, Post-Traumatic

Interventions: Balovaptan, Placebo

Sponsor: Hoffmann-La Roche | Started: 2022-08-02

A Study to Evaluate the Efficacy and Safety of Arbaclofen Placarbil (XP19986) as Adjunctive Therapy in Subjects With Gas Completed

PHASE2 NCT00978016 n=460

Gastroesophageal Reflux Disease

Interventions: arbaclofen placarbil-Cohort 1, Placebo-Cohort 5, arbaclofen placarbil-Cohort 2

Sponsor: XenoPort, Inc. | Started: 2009-09

A Study to Investigate the Effect of Itraconazole on the PK of Multiple Doses of Balovaptan in Healthy Volunteers Completed

PHASE1 NCT03579719 n=15

Healthy Volunteers

Interventions: Balovaptan, Itraconazole

Sponsor: Hoffmann-La Roche | Started: 2018-07-10

A Study Investigating the Absolute Oral Bioavailability of Balovaptan After Single and Multiple Daily Oral Doses of Balo Completed

PHASE1 NCT03764449 n=16

Healthy Volunteers

Interventions: Oral Balovaptan, IV Balovaptan

Sponsor: Hoffmann-La Roche | Started: 2019-01-10

A Study to Investigate the Effect of Rifampicin on the PK of Multiple Doses of Balovaptin In Healthy Volunteers Completed

PHASE1 NCT03586726 n=16

Healthy Volunteers

Interventions: Balovaptan, Rifampicin

Sponsor: Hoffmann-La Roche | Started: 2018-07-24

Modulation of the Brain Excitatory/Inhibitory (E/I) Balance in Autism Spectrum Disorder (ASD) Completed

NA NCT03594552 n=87

Autism Spectrum Disorder

Interventions: Arbaclofen_15, Arbaclofen_30, Placebo

Sponsor: King's College London | Started: 2018-02-01

Linked Hypotheses (2)

Trans-Synaptic Adhesion Molecule Modulation0.544

Trans-Synaptic Adhesion Molecule Modulation0.503

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

binds (1)

NLGN1→heparan sulfate

co discussed (10)

TREM2→NLGN1C3→NLGN1C1QA→NLGN1LAMP1→NLGN1NLGN1→ACSL4

▸ Show 5 more

ACSL4→NLGN1MOG→NLGN1NLGN1→TFEBNLGN1→TREM2NLGN1→C3

interacts with (3)

NLGN1→PSD95NLGN1→neurexinNRXN2A→NLGN1

involved in (1)

NLGN1→memory consolidation

participates in (1)

NLGN1→Synaptic function / plasticity

regulates (4)

NLGN1→Trans-Synaptic Adhesion Molecule ModulationNLGN1→GluA1FN→NLGN1Hevin→NLGN1

Debate History (1)

Should NLGN1 (Neuroligin-1) be prioritized as a therapeutic target for neurodege2026-04-22