Druggability & Clinical Context
Druggability
Low
Score: 0.44
Druggability Analysis
Structural Tractability0.85
Key Metrics
PDB Structures:
19
Known Drugs:
2
Approved:
0
In Clinical Trials:
0
Drug Pipeline (2 compounds)
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 ✓
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.
Clinical Trials (8)
Relevant trials from ClinicalTrials.gov
By Phase
PHASE1: 6 · PHASE2: 2
PHASE2
NCT01401062
n=23
Metastatic Breast Cancer
Interventions: Fresolimumab, Radiation Therapy
Sponsor: Weill Medical College of Cornell University | Started: 2011-07
PHASE2
NCT02008318
n=43
Myelodysplastic Syndromes
Interventions: Galunisertib, Placebo
Sponsor: Eli Lilly and Company | Started: 2014-03
PHASE1
NCT02581787
n=28
Stage IA Non-Small Cell Lung Carcinoma, Stage IB Non-Small Cell Lung Carcinoma
Interventions: Fresolimumab, Stereotactic Body Radiation Therapy
Sponsor: Maximilian Diehn | Started: 2016-08
PHASE1
NCT03064074
n=11
Osteogenesis Imperfecta
Interventions: Fresolimumab
Sponsor: Baylor College of Medicine | Started: 2017-11-15
PHASE1
NCT03206177
n=26
Carcinosarcoma, Ovarian
Interventions: Galunisertib, Paclitaxel, Carboplatin
Sponsor: University of Oklahoma | Started: 2017-08-23
PHASE1
NCT01373164
n=170
Neoplasms, Neoplasm Metastasis, Pancreatic Cancer
Interventions: Galunisertib, Gemcitabine, Placebo
Sponsor: Eli Lilly and Company | Started: 2011-06
PHASE1
NCT02752919
n=40
Healthy
Interventions: Galunisertib
Sponsor: Eli Lilly and Company | Started: 2016-04
PHASE1
NCT02423343
n=41
Solid Tumor, Non-Small Cell Lung Cancer Recurrent, Hepatocellular Carcinoma Recurrent
Interventions: Galunisertib, Nivolumab
Sponsor: Eli Lilly and Company | Started: 2015-01-01