PLA2G6

Phospholipase A2 group VI

Score: 0.487 Price: $0.49 Low Druggability Status: active Wiki: PLA2G6

🧠 Neurodegeneration

HYPOTHESES

1

PAPERS

22

KG EDGES

71

DEBATES

1

3D Protein Structure

🧬 PLA2G6 — PDB 2N3W Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.36

Clinical Stage

Approved

Target Class

Enzyme

Safety

0.30

Druggability Analysis

Drug Development0.75

Structural Tractability0.30

Target Class0.85

Safety Profile0.30

Key Metrics

PDB Structures:

0

Known Drugs:

2

Approved:

1

In Clinical Trials:

0

Drug Pipeline (2 compounds)

1 Approved

Druggability Rationale: PLA2G6 presents medium druggability (0.60) due to its well-defined enzyme class with a catalytic active site amenable to small molecule inhibition, supported by existing approved drugs (desipramine) and research tool compounds (bromoenol lactone) with demonstrated iPLA2 inhibitory activity. However, the lack of experimental structural data (no PDB entries, no cryo-EM) and reliance solely on AlphaFold predictions limit confidence in rational drug design, though the calcium-independent mechanism offers a distinct biochemical handle for inhibition.

Mechanism: Small molecule inhibitor of calcium-independent phospholipase A2 activity

Drug Pipeline (2 compounds)

1 Approved

Known Drugs:

Desipramine (approved) — Tricyclic antidepressant with iPLA2 inhibitory activity

Bromoenol lactone (research) — Selective iPLA2 inhibitor (tool compound)

Structural Data:

PDB —AlphaFold ✓Cryo-EM —

UniProt: A0A590UJC7

🧬 3D Protein Structure

🧬 PLA2G6 — PDB 2N3W Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

A major selectivity challenge is distinguishing PLA2G6 inhibition from other phospholipase A2 isoforms (PLA2G4, PLA2G5, etc.), as structural similarity across the family is high; selectivity will require detailed kinetic profiling and target engagement studies. Off-target liabilities with existing inhibitors like desipramine (tricyclic antidepressant with broad pharmacology) highlight the need for PLA2G6-selective scaffolds to avoid unintended neurological effects.

3D Protein Structure (AlphaFold)

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AlphaFold predicted structure available for A0A590UJC7

View AlphaFold Structure

Clinical Trials (8)

Relevant trials from ClinicalTrials.gov

Active

0

Completed

7

Total Enrollment

379

By Phase

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

Phase III Randomized Controlled Study of Morphine and Nortriptyline in the Management of Postherpetic Neuralgia Completed

PHASE3 NCT00004390 n=120

Pain, Herpes Zoster

Interventions: desipramine, methadone, morphine

Sponsor: National Center for Research Resources (NCRR) | Started: 1995-02

Study Evaluating the Effects of DVS SR and Paroxetine on the Pharmacokinetics of Desipramine in Healthy Subjects Completed

PHASE3 NCT00329147 n=20

Depression

Interventions: desvenlafaxine SR, desipramine, paroxetine

Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer | Started: 2006-05

Effect of Desipramine on Upper Airway Collapsibility and Genioglossus Muscle Activity in Patients With Obstructive Sleep Completed

PHASE2 NCT02436031 n=16

Sleep Apnea, Obstructive

Interventions: Desipramine, Placebo

Sponsor: Brigham and Women's Hospital | Started: 2015-04

Effect of Antidepressants on Back Pain Completed

PHASE2 NCT00018200 n=130

Back Pain, Sciatica

Interventions: Desipramine, Fluoxetine, Benztropine

Sponsor: US Department of Veterans Affairs | Started: 1999-04

Effect of Desipramine on Genioglossus Muscle Activity in Healthy Adults Study A Completed

PHASE2 NCT02428478 n=17

Sleep Apnea, Obstructive

Interventions: Desipramine, Placebo

Sponsor: Brigham and Women's Hospital | Started: 2015-03

To Demonstrate the Relative Bioavailability of Desipramine Hydrochloride Tablets Completed

PHASE1 NCT00913822 n=36

Depression

Interventions: Desipramine Hydrochloride 100 mg Tablets, Norpramin 100 mg Tablets (Merrell Dow Ph

Sponsor: Sandoz | Started: 1987-12

Study Evaluating the Pharmacokinetics of the Potential Drug Interaction Between HCV-796 and Desipramine Completed

PHASE1 NCT00500721 n=22

Healthy

Interventions: HCV-796, Desipramine

Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer | Started: 2007-06

Irritable Bowel Syndrome (IBS) Functional Magnetic Resonance Imaging (fMRI) With Desipramine Terminated

NA NCT00880594 n=18

Irritable Bowel Syndrome

Interventions: Desipramine

Sponsor: Washington University School of Medicine | Started: 2009-02

Linked Hypotheses (0)

No linked hypotheses

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

activates (1)

PLA2G6→PLA2G4A

associated with (2)

PLA2G6→neurodegenerationPLA2G6→PANK2

co discussed (14)

MMP9→PLA2G6SLC7A11→PLA2G6AQP4→PLA2G6CD38→PLA2G6C1Q→PLA2G6

▸ Show 9 more

NAMPT→PLA2G6GPX4→PLA2G6PLA2G6→MMP2PLA2G6→C3PLA2G6→PLA2G4ACGAS→PLA2G6PLA2G6→IL1BPLA2G6→DNASE2PLA2G6→STING1

inhibits (1)

PLA2G6→PLA2G4A

interacts with (2)

PLA2G6→PLA2G4APLA2G4A→PLA2G6

Debate History (1)

Should PLA2G6 (Phospholipase A2 group VI) be prioritized as a therapeutic target2026-04-22