SGMS2

Sphingomyelin synthase 2

Score: 0.477 Price: $0.48 Low Druggability Status: active Wiki: SGMS2

🧠 Neurodegeneration

HYPOTHESES

1

PAPERS

0

KG EDGES

6

DEBATES

1

3D Protein Structure

🔮 SGMS2 — AlphaFold Q8NHU3 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.29

Clinical Stage

Phase III

Target Class

Enzyme

Safety

0.50

Druggability Analysis

Drug Development0.45

Structural Tractability0.30

Target Class0.85

Safety Profile0.50

Key Metrics

PDB Structures:

0

Known Drugs:

1

Approved:

0

In Clinical Trials:

0

Drug Pipeline (1 compounds)

1 Preclinical

Druggability Rationale: SGMS2 presents medium druggability (0.55 score) as an enzyme target with a defined catalytic mechanism, supported by the existence of preclinical inhibitors like D609. However, the absence of experimental crystal structures (0 PDB entries) and reliance on AlphaFold predictions limit structure-based drug design optimization, though the well-characterized enzymatic mechanism of phosphocholine transfer to ceramide provides a clear binding hypothesis for active site inhibitors.

Mechanism: SGMS2 inhibitors would block the enzymatic transfer of phosphocholine to ceramide, reducing sphingomyelin biosynthesis and altering membrane composition and cellular signaling. This modulation could reduce pathological lipid accumulation and restore normal cell membrane dynamics in diseases characterized by sphingolipid dysregulation.

Drug Pipeline (1 compounds)

1 Preclinical

Known Drugs:

D609 (preclinical) — Tricyclodecan-9-yl xanthate, SMS inhibitor

Structural Data:

PDB —AlphaFold ✓Cryo-EM —

UniProt: Q8NHU3

🔮 Predicted Protein Structure (AlphaFold)

🔮 SGMS2 — AlphaFold Q8NHU3 Click to expand interactive 3D viewer

AI-predicted structure from AlphaFold EBI | Powered by Mol* | Rotate: click+drag | Zoom: scroll

Selectivity & Safety Considerations

Selectivity against the closely related SGMS1 isoform is a critical challenge given their shared catalytic function and substrate specificity, requiring careful medicinal chemistry to achieve isoform discrimination. Off-target effects on related sphingolipid enzymes (ceramide synthases, sphingosine-1-phosphate synthases) must be assessed given the interconnected nature of sphingolipid biosynthesis pathways.

3D Protein Structure (AlphaFold)

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AlphaFold predicted structure available for Q8NHU3

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Clinical Trials (8)

Relevant trials from ClinicalTrials.gov

Active

1

Completed

7

Total Enrollment

860

By Phase

NA: 5 · PHASE1: 1 · PHASE2: 1 · Unknown: 1

Anger Control Training for Youth With Tourette Syndrome Completed

NA NCT00486551 n=26

Tourette Syndrome, Chronic Tic Disorder, Oppositional Defiant Disorder

Interventions: Anger control training

Sponsor: Yale University | Started: 2001-08

Adaptive vs. Continuous Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease Recruiting

NA NCT06909045 n=130

Deep Brain Stimulation, Parkinson Disease

Interventions: Adaptive DBS, Continue DBS

Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC | Started: 2026-01-27

Expiratory Muscle Training in Patients With Parkinson's Disease Completed

PHASE1 NCT00843739 n=90

Parkinson's Disease

Interventions: EMST - Active Treatment, sham EMST

Sponsor: University of Florida | Started: 2004-01

Study of the Follow-up of Stroke Treated With Anticoagulants Completed

Unknown NCT03292575 n=441

Stroke

Interventions: Anticoagulants

Sponsor: Centre Hospitalier Universitaire Dijon | Started: 2016-01

Early Detection and Prevention of Mild Cognitive Impairment Due to Cerebrovascular Disease Completed

NA NCT01924312 n=80

Cerebrovascular Disease, Mild Cognitive Impairment

Interventions: Heart Health Intervention

Sponsor: Gregory Jicha, 323-5550 | Started: 2013-05

Effects of Modern Board Games on Well Being in Older Adults Completed

NA NCT06306365 n=35

Executive Functions

Interventions: Modern board game-based learning

Sponsor: European University Miguel de Cervantes | Started: 2024-02-07

Treatment of Alzheimer's and Dementia With the Metabolism, Infections, Nutrition, Drug Elimination (MIND) Protocol Completed

NA NCT02260167 n=25

Alzheimer's Disease, Dementia

Interventions: A mix of natural treatments and medicati

Sponsor: Practitioners Alliance Network | Started: 2014-09

A Phase 2 Study to Evaluate Safety of Long-term AL001 Dosing in Frontotemporal Dementia (FTD) Patients (INFRONT-2) Completed

PHASE2 NCT03987295 n=33

Frontotemporal Dementia

Interventions: AL001

Sponsor: Alector Inc. | Started: 2019-09-27

Linked Hypotheses (0)

No linked hypotheses

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

associated with (1)

SGMS2→neurodegeneration

co discussed (10)

FLOT1→SGMS2SREBF2→SGMS2CYP46A1→SGMS2SGMS2→ABCA1SGMS2→BACE1

▸ Show 5 more

SGMS2→ST3GAL2SGMS2→ST8SIA1SGMS2→LDLRSGMS2→SMPD1SGMS2→SGMS1

expressed in (1)

SGMS2→rat brain

implicated in (1)

SGMS2→neurodegeneration

interacts with (2)

SGMS1→SGMS2SGMS2→SGMS1

involved in (1)

SGMS2→sphingomyelin

participates in (1)

SGMS2→Sphingolipid / ceramide signaling

regulates (2)

SGMS2→ceramide metabolismSGMS2→drug transporters

targets (1)

h-fdb07848→SGMS2

Debate History (1)

Should SGMS2 (Sphingomyelin synthase 2) be prioritized as a therapeutic target f2026-04-22