ANXA1

Annexin A1

Score: 0.556 Price: $0.56 Low Druggability Status: active Wiki: ANXA1

🧠 Neurodegeneration

HYPOTHESES

1

PAPERS

25

KG EDGES

232

DEBATES

1

3D Protein Structure

🧬 ANXA1 — PDB 1HM6 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.41

Clinical Stage

Approved

Target Class

Signaling Protein

Safety

0.60

Druggability Analysis

Drug Development0.75

Structural Tractability0.70

Target Class0.50

Safety Profile0.60

Key Metrics

PDB Structures:

2

Known Drugs:

1

Approved:

1

In Clinical Trials:

0

Drug Pipeline (1 compounds)

1 Approved

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 —

UniProt: Q5T3N0

🧬 3D Protein Structure

🧬 ANXA1 — PDB 1HM6 Click to expand interactive 3D viewer

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

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.

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

4

Total Enrollment

2,241

By Phase

NA: 1 · PHASE1: 1 · PHASE2: 1 · PHASE3: 3 · Unknown: 2

Ixazomib Plus Lenalidomide Plus Dexamethasone for Newly Diagnosed Myeloma Patients Active Not Recruiting

PHASE2 NCT03376672 n=120

Multiple Myeloma

Interventions: Ixazomib, Lenalidomide, Dexamethasone

Sponsor: Raija Silvennoinen | Started: 2018-05-31

An Efficacy and Safety Study for Yondelis (Trabectedin) in Patients With Advanced Relapsed Ovarian Cancer Completed

PHASE3 NCT00113607 n=672

Ovarian Cancer

Interventions: Trabectedin, DOXIL, Dexamethasone

Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L | Started: 2005-04

Bortezomib, Selinexor, and Dexamethasone in Patients With Multiple Myeloma Completed

PHASE3 NCT03110562 n=402

Multiple Myeloma

Interventions: Selinexor, Bortezomib, Dexamethasone

Sponsor: Karyopharm Therapeutics Inc | Started: 2017-05-24

A Study of JNJ-54767414 (Daratumumab) in Combination With Lenalidomide and Dexamethasone in Japanese Participants With P Completed

PHASE1 NCT02918331 n=7

Multiple Myeloma

Interventions: Daratumumab (16 mg/kg), Lenalidomide, Dexamethasone

Sponsor: Janssen Pharmaceutical K.K. | Started: 2016-09

Perineural Dexamethasone for Continuous Femoral Nerve Block Completed

NA NCT05487001 n=18

Total Knee Arthroplasty

Interventions: dexamethasone group, sham group

Sponsor: Gangnam Severance Hospital | Started: 2022-08-09

A Chart Review of Rituximab Plus Repeated Cycles of Dexamethasone Terminated

Unknown NCT02050581 n=72

Idiopathic Thrombocytopenia Purpura

Sponsor: Weill Medical College of Cornell University | Started: 2011-01

Daunorubicin, Cytarabine, and Midostaurin in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Unknown

PHASE3 NCT00651261 n=717

Leukemia

Interventions: cytarabine, daunorubicin, midostaurin

Sponsor: Alliance for Clinical Trials in Oncology | Started: 2008-04

Determining the Long-Term Effects of Prenatal Dexamethasone Treatment in Children With 21-Hydroxylase Deficiency and The Unknown

Unknown NCT00617292 n=233

Adrenal Hyperplasia, Congenital

Sponsor: Office of Rare Diseases (ORD) | Started: 2008-01

Linked Hypotheses (1)

Synaptic Phosphatidylserine Masking via Annexin A1 Mimetics0.625

Linked Experiments (4)

Identified a subtype of Sox6+ Anxa1+ dopaminergic neurons that are selectively lost earlier than oth0.500

Generated a knock-in Cre mouse line for Anxa1+ dopaminergic neurons to enable targeted manipulation 0.500

Mapped differential anatomical inputs and outputs of Anxa1+ dopaminergic neurons compared to other D0.500

Inhibition of transmitter release specifically in Anxa1+ neurons was sufficient to induce bradykines0.500

Scoring Dimensions

Knowledge Graph (20)

activates (3)

ANXA1→NBR1ANXA1→STINGNBR1→ANXA1

associated with (2)

ANXA1→neurodegenerationCASP3→ANXA1

co discussed (5)

HK2→ANXA1TREM2→ANXA1P2RY12→ANXA1C1QA→ANXA1ANXA1→CX3CR1

expressed in (1)

inhibits (1)

protects against (1)

regulates (2)

ANXA1→MTORANXA1→OVERVIEW

therapeutic target (5)

ANXA1→CX3CR1ANXA1→TNFJUN→ANXA1TNF→ANXA1CX3CR1→ANXA1

Debate History (1)

Should ANXA1 (Annexin A1) be prioritized as a therapeutic target for neurodegene2026-04-21