IDH2

Isocitrate Dehydrogenase 2

Score: 0.691 Price: $0.69 High Druggability Status: active Wiki: IDH2

🧠 Neurodegeneration

HYPOTHESES

2

PAPERS

31

KG EDGES

166

DEBATES

1

3D Protein Structure

🧬 IDH2 — PDB 5I95 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

High

Score: 0.90

Clinical Stage

Approved

Target Class

Enzyme

Safety

0.60

Druggability Analysis

Drug Development0.60

Structural Tractability0.85

Target Class0.85

Safety Profile0.60

Key Metrics

PDB Structures:

12

Known Drugs:

2

Approved:

0

In Clinical Trials:

0

Drug Pipeline (2 compounds)

Druggability Rationale: IDH2 is highly druggable (score: 0.90) due to its well-defined active site suitable for small molecule inhibition, strong structural characterization with 12 PDB structures at 1.54 Å resolution, and clinical validation via two FDA-approved drugs (Enasidenib, Ivosidenib) targeting mutant IDH2 in AML. The enzyme's role as a metabolic checkpoint with a conserved catalytic pocket makes it amenable to selective inhibitor design.

Mechanism: Small molecule inhibitor of mutant IDH2 enzyme activity

Drug Pipeline (2 compounds)

Known Drugs:

Enasidenib (Approved) — Acute myeloid leukemia

Ivosidenib (Approved) — Acute myeloid leukemia

Structural Data:

PDB (12) ✓AlphaFold ✓Cryo-EM —

3BLV 3BLW 3BLX 4JA8 5H3E+7 more

UniProt: A0A1P8A7C0

🧬 3D Protein Structure

🧬 IDH2 — PDB 5I95 Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

Selectivity between IDH2 and the cytosolic isoform IDH1 is critical to avoid off-target metabolic disruption; existing approved drugs achieve this through mitochondrial-targeting and mutant-selective binding modes. Cross-reactivity with other TCA cycle dehydrogenases (IDH1, SDH) requires careful structural optimization to minimize systemic metabolic toxicity.

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

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 (1)

Grid Cell-Specific Metabolic Reprogramming via IDH2 Enhancement0.646

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

activates (2)

IDH2→GAINGAIN→IDH2

associated with (2)

IDH2→neurodegenerationIDH1→IDH2

co discussed (6)

RELN→IDH2MAP6→IDH2HCN1→IDH2MCU→IDH2PPARGC1A→IDH2

▸ Show 1 more

implicated in (4)

IDH2→ADIDH2→ALIIDH2→AMIIDH2→glioma

inhibits (1)

regulates (1)

IDH2→Grid Cell-Specific Metabolic Reprogramming via IDH

therapeutic target (4)

TIGAR→IDH2IDH2→TKTTKT→IDH2IDH2→TIGAR

Debate History (1)

Should IDH2 (Isocitrate Dehydrogenase 2) be prioritized as a therapeutic target 2026-04-21