Druggability & Clinical Context
Druggability
Low
Score: 0.41
Target Class
Signaling Protein
Druggability Analysis
Structural Tractability0.70
Key Metrics
PDB Structures:
2
Known Drugs:
1
Approved:
1
In Clinical Trials:
0
Drug Pipeline (1 compounds)
1 Approved
Therapeutic Areas:Alzheimer's disease Neuroinflammation Microglial dysfunction Neuroprotection Neuroimmunology General anti-inflammatory disorders
Druggability Rationale: ANXA1 presents moderate-to-low druggability challenges due to its function as a signaling protein lacking a well-defined enzymatic active site, combined with a low druggability score of 0.30. However, the existence of approved indirect modulators (dexamethasone) and available crystal structures (PDB: 1MCX, 9NP0 at 2.3Å resolution) demonstrate proof-of-concept for pharmacological intervention, suggesting that direct modulation of protein-protein interactions or phospholipid binding may be achievable with targeted approaches.
Mechanism: Calcium-dependent phospholipid binding protein modulator
Drug Pipeline (1 compounds)
1 Approved
Known Drugs:Dexamethasone (approved) — Anti-inflammatory (indirect ANXA1 upregulation)
Structural Data:PDB (2) ✓AlphaFold ✓Cryo-EM —
Binding Pocket Analysis:ANXA1 possesses calcium-dependent phospholipid binding sites characterized by positively charged amino acid clusters that coordinate both Ca2+ ions and phosphodiester moieties. Allosteric modulation sites may exist outside the core binding pocket, potentially enabling selective small-molecule modulators that enhance or inhibit protein-protein interactions without directly competing with phospholipid binding.
Selectivity & Safety Considerations
Selectivity challenges include potential cross-reactivity with other annexin family members (ANXA2-ANXA11), which share structural homology in their core phospholipid-binding domains. Isoform selectivity will be critical for avoiding off-target effects on broader calcium signaling pathways and inflammatory responses mediated by related annexins.
Clinical Trials (8)
Relevant trials from ClinicalTrials.gov
By Phase
NA: 1 · PHASE1: 1 · PHASE2: 1 · PHASE3: 3 · Unknown: 2
PHASE2
NCT03376672
n=120
Multiple Myeloma
Interventions: Ixazomib, Lenalidomide, Dexamethasone
Sponsor: Raija Silvennoinen | Started: 2018-05-31
PHASE3
NCT00113607
n=672
Ovarian Cancer
Interventions: Trabectedin, DOXIL, Dexamethasone
Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L | Started: 2005-04
PHASE3
NCT03110562
n=402
Multiple Myeloma
Interventions: Selinexor, Bortezomib, Dexamethasone
Sponsor: Karyopharm Therapeutics Inc | Started: 2017-05-24
PHASE1
NCT02918331
n=7
Multiple Myeloma
Interventions: Daratumumab (16 mg/kg), Lenalidomide, Dexamethasone
Sponsor: Janssen Pharmaceutical K.K. | Started: 2016-09
NA
NCT05487001
n=18
Total Knee Arthroplasty
Interventions: dexamethasone group, sham group
Sponsor: Gangnam Severance Hospital | Started: 2022-08-09
Unknown
NCT02050581
n=72
Idiopathic Thrombocytopenia Purpura
Sponsor: Weill Medical College of Cornell University | Started: 2011-01
PHASE3
NCT00651261
n=717
Leukemia
Interventions: cytarabine, daunorubicin, midostaurin
Sponsor: Alliance for Clinical Trials in Oncology | Started: 2008-04
Unknown
NCT00617292
n=233
Adrenal Hyperplasia, Congenital
Sponsor: Office of Rare Diseases (ORD) | Started: 2008-01