LOXL1-4

Lysyl oxidase-like 1-4

Score: 0.456 Price: $0.46 Low Druggability Status: active Wiki: LOXL1-4

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

DEBATES

3D Protein Structure

🔮 LOXL1-4 — AlphaFold Q08397 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.33

Clinical Stage

Phase II

Target Class

Enzyme

Safety

0.50

Druggability Analysis

Drug Development0.35

Structural Tractability0.30

Target Class0.85

Safety Profile0.50

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (3 compounds)

1 Phase II · 2 Preclinical

Druggability Rationale: LOXL1-4 demonstrates medium druggability (0.50) despite lacking crystal structures, supported by the advancement of small molecule inhibitors (PXS-5153A) and monoclonal antibodies (Simtuzumab) into preclinical and Phase 2 stages. The copper-dependent catalytic domain presents a tractable binding pocket for small molecule inhibition, though the absence of PDB structures and limited structural data somewhat constrain rational drug design efforts.

Mechanism: Small molecule enzyme inhibitors targeting the catalytic domain

Drug Pipeline (3 compounds)

1 Phase II · 2 Preclinical

Known Drugs:

BAPN (research_tool)

PXS-5153A (preclinical)

Simtuzumab (phase_2)

Structural Data:

PDB —AlphaFold ✓Cryo-EM —

🔮 Predicted Protein Structure (AlphaFold)

🔮 LOXL1-4 — AlphaFold Q08397 Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

Selectivity among the four LOXL isoforms (LOXL1-4) remains a significant challenge given their structural homology and overlapping catalytic mechanisms, requiring careful optimization to avoid off-target effects on the canonical LOX enzyme. Achieving isoform-selective inhibition will be critical for reducing potential compensatory pathway activation and systemic side effects related to collagen crosslinking in peripheral tissues.

Clinical Trials (6)

Relevant trials from ClinicalTrials.gov

Active

Completed

Total Enrollment

1,074

By Phase

PHASE2: 6

Pilot Study of Simtuzumab in the Treatment of Liver Fibrosis Completed

PHASE2 NCT01452308 n=20

Liver Fibrosis

Interventions: Simtuzumab

Sponsor: Gilead Sciences | Started: 2011-11

Safety, Tolerability, and Efficacy of GS-4997 Alone or in Combination With Simtuzumab (SIM) in Adults With Nonalcoholic Completed

PHASE2 NCT02466516 n=72

Non-Alcoholic Steatohepatitis (NASH)

Interventions: SEL, SIM

Sponsor: Gilead Sciences | Started: 2015-06-08

Simtuzumab (GS-6624) in the Prevention of Progression of Liver Fibrosis in Adults With Primary Sclerosing Cholangitis (P Completed

PHASE2 NCT01672853 n=235

Primary Sclerosing Cholangitis (PSC)

Interventions: Simtuzumab, Placebo

Sponsor: Gilead Sciences | Started: 2013-03-04

Efficacy and Safety of Simtuzumab (SIM) With FOLFIRI as Second Line Treatment in Colorectal Adenocarcinoma Terminated

PHASE2 NCT01479465 n=266

Colorectal Cancer

Interventions: Simtuzumab, Placebo to match SIM, Leucovorin

Sponsor: Gilead Sciences | Started: 2011-12

Safety and Efficacy of Simtuzumab (SIM, GS-6624) in Adults With Advanced Liver Fibrosis But Not Cirrhosis Secondary to N Terminated

PHASE2 NCT01672866 n=222

Liver Fibrosis Due to NASH

Interventions: Placebo, SIM

Sponsor: Gilead Sciences | Started: 2012-12-05

Simtuzumab (SIM, GS-6624) in the Treatment of Cirrhosis Due to NASH Terminated

PHASE2 NCT01672879 n=259

Liver Fibrosis Due to NASH

Interventions: Placebo, SIM

Sponsor: Gilead Sciences | Started: 2012-10-29

Linked Hypotheses (0)

No linked hypotheses

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

associated with (2)

LOXL1-4→neurodegenerationLOX→LOXL1-4

co discussed (10)

AQP1→LOXL1-4KCNK2→LOXL1-4GJA1→LOXL1-4HCRTR2→LOXL1-4LOXL1-4→HCRTR1

▸ Show 5 more

LOXL1-4→AQP4LOXL1-4→LOXLOXL1-4→SDC1LOXL1-4→PDGFRBHCRTR1→LOXL1-4

Debate History (1)

Should LOXL1-4 (Lysyl oxidase-like 1-4) be prioritized as a therapeutic target f2026-04-22