TNFA

Tumor necrosis factor alpha

Score: 0.577 Price: $0.58 Medium Druggability Status: active Wiki: TNFA

🧠 Neurodegeneration

HYPOTHESES

2

PAPERS

18

KG EDGES

180

DEBATES

1

3D Protein Structure

🧬 TNFA — PDB 1TNF Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.50

Clinical Stage

Approved

Target Class

Signaling Protein

Safety

0.40

Druggability Analysis

Drug Development1.00

Structural Tractability0.85

Target Class0.50

Safety Profile0.40

Key Metrics

PDB Structures:

41

Known Drugs:

3

Approved:

3

In Clinical Trials:

0

Drug Pipeline (3 compounds)

3 Approved

Druggability Rationale: This signaling protein has druggable allosteric or catalytic sites with established pharmacological validation, making it amenable to small molecule intervention. Crystal structures available (41 PDB entries) supporting structure-based drug design. AlphaFold predicted structure available for computational screening. 3 approved drug(s) validate this target pharmacologically.

Mechanism: Monoclonal antibodies or soluble receptors that neutralize TNF-alpha activity

Drug Pipeline (3 compounds)

3 Approved

Known Drugs:

Etanercept (approved) — Rheumatoid arthritis (CNS trials conducted)

Infliximab (approved) — Inflammatory diseases

Adalimumab (approved) — Inflammatory diseases

Structural Data:

PDB (41) ✓AlphaFold ✓Cryo-EM ✓

2AZ5 2ZJC 2ZPX 3ALQ 3WD5+36 more

UniProt: P01375

🧬 3D Protein Structure

🧬 TNFA — PDB 1TNF Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

Selectivity within signaling cascades is important to avoid disrupting essential cellular processes. Pathway-selective approaches are preferred.

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

4

Completed

4

Total Enrollment

1,152

By Phase

PHASE1: 2 · PHASE3: 2 · PHASE4: 3 · Unknown: 1

STep-up and Step-down Therapeutic Strategies in Childhood ARthritiS Recruiting

PHASE3 NCT03728478 n=260

Oligoarthritis, Juvenile, Polyarthritis, Juvenile, Rheumatoid Fact

Interventions: Etanercept, Methotrexate, Intra-articular corticosteroid injection

Sponsor: Istituto Giannina Gaslini | Started: 2019-05-29

Topical Infliximab in Eyes With Penetrating Keratoplasty Recruiting

PHASE1 NCT05180994 n=50

Glaucoma Following Surgery

Interventions: Topical infliximab, No topical infliximab

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM) | Started: 2022-05-01

A Study of Adalimumab in Acute Vogt-Koyanagi-Harada Disease Recruiting

Unknown NCT05590416 n=15

Vogt-Koyanagi-Harada Disease, Adalimumab

Interventions: Adalimumab

Sponsor: Tianjin Medical University | Started: 2021-06-01

Safety of a Strategy Combining Etanercept Administration with Repeated Contrast Ultrasound in Patients with Alzheimer's Not Yet Recruiting

PHASE1 NCT06585384 n=5

Alzheimer Disease

Interventions: etanercept and repeated contrast ultraso

Sponsor: Fondation Ophtalmologique Adolphe de Rothschild | Started: 2025-03

Study Conducted in Subjects With Rheumatoid Arthritis Who Have Moderate to Severe Disease Activity Despite Methotrexate Completed

PHASE4 NCT01578850 n=491

Rheumatoid Arthritis

Interventions: Etanercept, placebo

Sponsor: Pfizer | Started: 2012-07

Salvage Therapy With High/Low Methotrexate for Loss of Response to Infliximab Dose Escalation Completed

PHASE4 NCT02269358 n=22

Crohn's Disease

Interventions: METHOTREXATE

Sponsor: Prof. Arie Levine | Started: 2015-07

Humira in Rheumatoid Arthritis - Do Bone Erosions Heal? Completed

PHASE4 NCT00696059 n=52

Rheumatoid Arthritis, Arthritis, Joint Diseases

Interventions: Adalimumab (Humira)

Sponsor: Hvidovre University Hospital | Started: 2004-08

16.0040 Ankylosing Spondylitis Study Completed

PHASE3 NCT00356356 n=257

Ankylosing Spondylitis

Interventions: Etanercept

Sponsor: Amgen | Started: 2002-04

Linked Hypotheses (0)

No linked hypotheses

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

associated with (1)

TNFA→neurodegeneration

co discussed (14)

FOXP3→TNFATNFA→PPARGC1ATNFA→PRKAA1TNFA→NR3C1TNFA→DRD2

▸ Show 9 more

TNFA→CHR2TNFA→CLOCKTNFA→CRHTNFA→BDNFTNFA→SNCATNFA→ANGPT1TNFA→ULK1TNFA→PDGFRBTNFA→TGFB1

inhibits (1)

interacts with (4)

NR3C1→TNFACRH→TNFATNFA→NR3C1TNFA→CRH

Debate History (1)

Should TNFA (Tumor necrosis factor alpha) be prioritized as a therapeutic target2026-04-21