MMP9

Matrix metalloproteinase-9

Score: 0.585 Price: $0.58 Medium Druggability Status: active Wiki: MMP9

🧠 Neurodegeneration

HYPOTHESES

1

PAPERS

22

KG EDGES

985

DEBATES

1

3D Protein Structure

🧬 MMP9 — PDB 1L6J Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.54

Clinical Stage

Phase III

Target Class

Protease

Safety

0.30

Druggability Analysis

Drug Development0.45

Structural Tractability0.85

Target Class0.85

Safety Profile0.30

Key Metrics

PDB Structures:

25

Known Drugs:

2

Approved:

0

In Clinical Trials:

0

Drug Pipeline (2 compounds)

Druggability Rationale: MMP9 is highly druggable (0.80 score) as a validated protease target with extensive structural data (25 PDB structures, 1.1 Å resolution), well-characterized zinc-dependent catalytic mechanism, and proven small molecule tractability. However, clinical translation has been challenged by lack of efficacy in Phase 3 oncology trials (Marimastat, Andecaliximab), suggesting that target inhibition alone may be insufficient or that CNS penetration and off-target MMP inhibition complicate therapeutic benefit.

Mechanism: Small molecule zinc-chelating inhibitors or antibody-based inhibition

Drug Pipeline (2 compounds)

Known Drugs:

Marimastat (failed_phase_3) — cancer

Andecaliximab (failed_phase_3) — cancer

Structural Data:

PDB (25) ✓AlphaFold ✓Cryo-EM —

2OVX 2OVZ 2OW0 2OW1 2OW2+20 more

UniProt: P14780

🧬 3D Protein Structure

🧬 MMP9 — PDB 1L6J Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

MMP9 selectivity is a major challenge due to high sequence homology with MMP2 (72% identity in catalytic domain) and other gelatinases; pan-MMP inhibitors showed poor clinical outcomes, necessitating isoform-selective scaffolds. Off-target inhibition of related MMPs may cause connective tissue toxicity and impair physiological remodeling, a key limitation of first-generation inhibitors like Marimastat.

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

2

Completed

6

Total Enrollment

1,792

By Phase

PHASE1: 3 · PHASE2: 2 · PHASE3: 3

A Study of Andecaliximab in People With Spinal Cord Injury at Risk for Bone Growth Outside of the Normal Skeleton. Recruiting

PHASE1 NCT07024407 n=10

Heterotopic Ossification (HO)

Interventions: Andecaliximab

Sponsor: Ashibio Inc | Started: 2025-05-14

Trial of Oral Community SVMP INhibitors for Snakebite Not Yet Recruiting

PHASE2 NCT07500233 n=504

Snakebite

Interventions: 2,3-dimercapto-1-propanesulfonic acid, marimastat, Oral placebo capsules

Sponsor: Liverpool School of Tropical Medicine | Started: 2027-01

Marimastat or No Further Therapy in Treating Women With Metastatic Breast Cancer That Is Responding or Stable Following Completed

PHASE3 NCT00003010 n=334

Breast Cancer

Interventions: marimastat

Sponsor: Eastern Cooperative Oncology Group | Started: 1997-12-02

Marimastat in Treating Patients With Stage III Non-small Cell Lung Cancer Completed

PHASE3 NCT00002911

Lung Cancer

Interventions: marimastat

Sponsor: ILEX Oncology Services, Incorporated | Started: 1996-12

Marimastat Following Chemotherapy in Treating Patients With Small Cell Lung Cancer Completed

PHASE3 NCT00003011 n=555

Lung Cancer

Interventions: marimastat, Placebo

Sponsor: NCIC Clinical Trials Group | Started: 1997-01-31

Study to Evaluate the Efficacy and Safety of Andecaliximab Combined With Nivolumab Versus Nivolumab Alone in Adults With Completed

PHASE2 NCT02864381 n=144

Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma

Interventions: Andecaliximab, Nivolumab

Sponsor: Gilead Sciences | Started: 2016-09-01

Phase I Drug Trial for S/E of Marimastat in Disabling Malformations When no Other Options. Completed

PHASE1 NCT00261391 n=9

Vascular Anomalies

Interventions: Marimastat

Sponsor: Boston Children's Hospital | Started: 2000-10

Study to Evaluate the Safety and Tolerability of Andecaliximab as Monotherapy and in Combination With Chemotherapy in Pa Completed

PHASE1 NCT01803282 n=236

Pancreatic Cancer, Non-small Cell Lung Cancer, Esophagogastric Cancer

Interventions: Andecaliximab, Gemcitabine, Nab-paclitaxel

Sponsor: Gilead Sciences | Started: 2013-03-29

Linked Hypotheses (0)

No linked hypotheses

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

associated with (1)

MMP9→neurodegeneration

co discussed (14)

MMP9→SLC7A11MMP9→AQP4MMP9→CD38MMP9→C1QMMP9→NAMPT

▸ Show 9 more

MMP9→GPX4MMP9→PLA2G6MMP9→MMP2MMP9→C3MMP9→PLA2G4AMMP9→CGASMMP9→IL1BMMP9→DNASE2MMP9→STING1

interacts with (3)

MMP2→MMP9MMP9→MMP2MMP9→TNF

regulates (2)

AKT_MTOR_PATHWAY→MMP9STAT3→MMP9

Debate History (1)

Should MMP9 (Matrix metalloproteinase-9) be prioritized as a therapeutic target 2026-04-21