TGFB1

Transforming growth factor beta-1

Score: 0.626 Price: $0.63 Low Druggability Status: active Wiki: TGFB1

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

317

DEBATES

3D Protein Structure

🧬 TGFB1 — PDB 3KFD Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.44

Clinical Stage

Phase III

Target Class

Ligand

Safety

0.30

Druggability Analysis

Drug Development0.45

Structural Tractability0.85

Target Class0.50

Safety Profile0.30

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (2 compounds)

Therapeutic Areas:

Neurodegeneration (Alzheimer's disease) Multiple sclerosis Pulmonary fibrosis Hepatic fibrosis Oncology (solid tumors) Chronic inflammation Neuroinflammation Gliosis-related disorders

Druggability Rationale: TGFB1 demonstrates high druggability (0.80 score) due to its well-characterized protein structure with 19 PDB entries at 2.21 Å resolution, enabling rational design of both monoclonal antibodies and small molecule inhibitors. The existence of clinical-stage candidates (Fresolimumab, Galunisertib) and proven ligand-binding mechanisms validate target tractability, though the pleiotropic nature of TGF-β signaling necessitates careful therapeutic window management.

Mechanism: Monoclonal antibodies neutralizing TGF-β1 or small molecule inhibitors of TGF-β signaling

Drug Pipeline (2 compounds)

Known Drugs:

Fresolimumab (Clinical trials) — Fibrosis

Galunisertib (Clinical trials) — Cancer

Structural Data:

PDB (19) ✓AlphaFold ✓Cryo-EM ✓

3KFD 4KV5 5FFO 5VQF 5VQP+14 more

UniProt: A0A7I2YQL8

Binding Pocket Analysis:

TGFB1 features a characteristic cytokine binding interface recognized by neutralizing antibody epitopes mapped in crystal structures (3KFD, 4KV5), with a buried hydrophobic core stabilized by multiple disulfide bonds. Small molecule inhibitors typically target the type I/II receptor binding surfaces or allosteric pockets rather than a classical ATP-binding site, as revealed by cryo-EM and high-resolution structural data.

🔮 Predicted Protein Structure (AlphaFold)

🔮 TGFB1 — AlphaFold P01137 Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

TGF-β1 selectivity over TGF-β2 and TGF-β3 isoforms is critical, as pan-TGF-β inhibition may cause immunosuppression and increased infection risk. Monoclonal antibodies offer superior isoform selectivity compared to receptor antagonists, though small molecule inhibitors targeting downstream signaling (ALK5) may lack TGFB1-specific discrimination.