LRP1

LDL receptor related protein 1

Score: 0.549 Price: $0.55 Low Druggability Status: active Wiki: LRP1

🧠 Neurodegeneration

HYPOTHESES

12

PAPERS

51

KG EDGES

752

DEBATES

1

3D Protein Structure

🧬 LRP1 — PDB 2FCW Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.39

Clinical Stage

Phase III

Target Class

Receptor

Safety

0.40

Druggability Analysis

Drug Development0.45

Structural Tractability0.85

Target Class0.70

Safety Profile0.40

Key Metrics

PDB Structures:

10

Known Drugs:

2

Approved:

0

In Clinical Trials:

0

Drug Pipeline (2 compounds)

1 Preclinical

Druggability Rationale: LRP1's low druggability stems from its complex multidomain structure and large molecular weight, which complicates traditional small molecule targeting approaches. While research molecules like receptor-associated protein (RAP) and preclinical antibodies demonstrate potential modulation strategies, the receptor's extensive endocytic and signaling roles necessitate highly specific interventions to avoid off-target effects in neurodegenerative contexts. The availability of multiple PDB structures and AlphaFold predictions provides promising structural insights, but translating these into clinically viable therapeutic agents remains challenging given LRP1's intricate biological functions.

Mechanism: Modulation of receptor-mediated endocytosis and clearance pathways

Drug Pipeline (2 compounds)

1 Preclinical

Known Drugs:

Receptor-associated protein (RAP) (research) — Endogenous LRP1 antagonist, blocks ligand binding

Anti-LRP1 antibodies (preclinical) — Function-blocking antibodies for tau uptake prevention

Structural Data:

PDB (10) ✓AlphaFold ✓Cryo-EM —

2FYJ 2FYL 2KNX 2KNY 4WFC+5 more

UniProt: Q07954

🧬 3D Protein Structure

🧬 LRP1 — PDB 2FCW Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

Receptor subtype selectivity is essential for therapeutic efficacy and safety. Cross-reactivity with related receptors should be profiled early in drug discovery.

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 (6)

Relevant trials from ClinicalTrials.gov

Active

2

Completed

3

Total Enrollment

1,633

By Phase

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

Aquaporin-4 Single Nucleotide Polymorphisms in Patients With Idiopathic and Familial Parkinson's Disease Active Not Recruiting

Unknown NCT04553185 n=800

Parkinson Disease

Interventions: Study procedure

Sponsor: University of Exeter

Non-inferiority Study of Ocrelizumab and Rituximab in Active Multiple Sclerosis Active Not Recruiting

PHASE3 NCT04688788 n=600

Relapsing Remitting Multiple Sclerosis, Secondary Progressive Multiple Sclerosis, Primary Progressive Multiple Sclerosis

Interventions: Rituximab, Ocrelizumab, Fexofenadine

Sponsor: Rigshospitalet, Denmark

GRN1005 Alone or in Combination With Trastuzumab in Breast Cancer Patients With Brain Metastases Completed

PHASE2 NCT01480583 n=85

Breast Cancer, Brain Metastases

Interventions: GRN1005, Trastuzumab, 18F-FLT

Sponsor: Angiochem Inc

GRN1005 in Non-Small Cell Lung Cancer (NSCLC) Patients With Brain Metastases (GRABM-L) Terminated

PHASE2 NCT01497665 n=16

Non-small Cell Lung Cancer (NSCLC) With

Interventions: GRN1005

Sponsor: Angiochem Inc

ANG1005 in Breast Cancer Patients With Recurrent Brain Metastases Completed

PHASE2 NCT02048059 n=72

Breast Cancer, Brain Metastases

Interventions: ANG1005

Sponsor: Angiochem Inc

Macronutrient Effects on Alzheimer's Disease (MEAL-2) Completed

NA NCT02463084 n=60

Prediabetic State, Insulin Resistance, Middle Age

Interventions: Low Diet, High Diet

Sponsor: Wake Forest University Health Sciences

Linked Hypotheses (10)

LRP1-Dependent Tau Uptake Disruption0.808

Astrocyte LRP1-mediated tau uptake and APOE4-dependent secretion creates regional susceptibility gra0.610

LRP1-mediated tau uptake disruption as an initiator of early tau propagation requires proximal valid0.604

LRP1-Dependent Tau Uptake Disruption0.600

Blocking Exosomal Tau Uptake at Neuronal LRP1 Receptors Disrupts Interneuronal Propagation0.570

LRP1-mediated synaptic uptake drives early entorhinal-hippocampal tau propagation (Braak I-II)0.570

LRP1 Loss-of-Function Derepresses P2RY12 Expression0.500

Soluble LRP1 Fragments Serve as Blood-Based Indicators of Impaired Aβ Efflux and BBB Transporter Dys0.485

CNS-Peripheral Cytokine Compartmentalization0.455

Poorly lipidated APOE4 particles are preferentially routed through LDLR/LRP1 into a nonproductive en0.340

Linked Experiments (1)

Meta-analysis of LRP1 C766T polymorphism and Alzheimer's disease susceptibility0.950

Scoring Dimensions

Knowledge Graph (20)

co discussed (6)

LRP1→LDLRLRP1→TFR1LRP1→AQP4LRP1→CAV1LRP1→ABCB1

▸ Show 1 more

interacts with (14)

TFR1→LRP1LRP1→TFR1LRP1→CAV1LRP1→ABCB1CAV1→LRP1

▸ Show 9 more

ABCB1→LRP1LRP1→MTNR1ALRP1→MTNR1BMTNR1A→LRP1MTNR1B→LRP1APOE→LRP1LRP1→APOELRP1→LDLRLDLR→LRP1

Debate History (1)

Should LRP1 (LDL receptor related protein 1) be prioritized as a therapeutic tar2026-04-22