HSPG2

Heparan Sulfate Proteoglycan 2

Score: 0.504 Price: $0.50 Low Druggability Status: active Wiki: HSPG2

🧠 Neurodegeneration

HYPOTHESES

1

PAPERS

24

KG EDGES

139

DEBATES

0

3D Protein Structure

🧬 HSPG2 — PDB 3B4U Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.38

Clinical Stage

Phase II

Target Class

Structural Protein

Safety

0.30

Druggability Analysis

Drug Development0.30

Structural Tractability0.70

Target Class0.50

Safety Profile0.30

Key Metrics

PDB Structures:

2

Known Drugs:

2

Approved:

0

In Clinical Trials:

0

Drug Pipeline (2 compounds)

2 Preclinical

Druggability Rationale: HSPG2 presents a challenging druggability profile (0.30 score) due to its large, flexible structural nature as a basement membrane proteoglycan with multiple functional domains rather than a discrete ligand-binding pocket. While heparan sulfate interactions offer a modulation strategy demonstrated by investigational agents like PI-88, the target's complexity and limited precedent for small-molecule inhibitors make traditional drug discovery approaches difficult; however, biologics and heparan sulfate mimetics represent viable alternative modalities.

Mechanism: Targeting protein-heparan sulfate interactions or enzymatic modification

Drug Pipeline (2 compounds)

2 Preclinical

Known Drugs:

Heparanase inhibitors (preclinical) — Perlecan modulators via heparan sulfate processing

PI-88 (investigational) — Heparan sulfate mimetic, modulates HSPG2 function

Structural Data:

PDB (2) ✓AlphaFold ✓Cryo-EM —

UniProt: P98160

🧬 3D Protein Structure

🧬 HSPG2 — PDB 3B4U 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 distinguishing HSPG2-specific effects from other heparan sulfate proteoglycans (HSPG1/SDC1-4) that share similar binding motifs and extracellular matrix localization. Off-target liabilities may arise from broad interactions with heparin-binding proteins and coagulation factors, requiring careful pharmacological profiling.

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

0

Completed

6

Total Enrollment

1,632

By Phase

PHASE1: 2 · PHASE2: 4 · PHASE3: 2

Trial of PI-88 With Dacarbazine in Patients With Metastatic Melanoma Completed

PHASE2 NCT00130442 n=134

Melanoma

Interventions: PI-88 and dacarbazine, dacarbazine or DTIC

Sponsor: Cellxpert Biotechnology Corp. | Started: 2005-06

Pilot Efficacy Study of PI-88 With Docetaxel to Treat Prostate Cancer Completed

PHASE2 NCT00268593 n=48

Prostate Cancer

Interventions: PI-88, docetaxel, prednisone

Sponsor: Progen Pharmaceuticals | Started: 2005-08

Docetaxel With or Without PI-88 in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer Completed

PHASE2 NCT00103389 n=98

Lung Cancer

Interventions: PI-88, docetaxel

Sponsor: Cellxpert Biotechnology Corp. | Started: 2004-02

Trial of PI-88 With Docetaxel in Advanced Non-Small-Cell Lung Cancer (NSCLC) Completed

PHASE2 NCT00097851 n=100

Carcinoma, Non-Small-Cell Lung

Interventions: docetaxel, PI-88

Sponsor: Cellxpert Biotechnology Corp. | Started: 2004-02

PI-88 in Treating Patients With an Advanced Malignancy (Cancer) or Stage IV Melanoma Completed

PHASE1 NCT00073892 n=44

Melanoma (Skin), Unspecified Adult Solid Tumor, Protocol

Interventions: PI-88

Sponsor: Cellxpert Biotechnology Corp. | Started: 2004-01

Study of PI-88 in Patients With Advanced Melanoma Completed

PHASE1 NCT00068172 n=88

Melanoma

Interventions: PI-88

Sponsor: Cellxpert Biotechnology Corp. | Started: 2001-07

A Phase III PI-88 in the Adjuvant Treatment of Subjects With Hepatitis Virus Related HCC After Surgical Resection Terminated

PHASE3 NCT01402908 n=520

Cancer, Liver Cancer, Hepatocellular Carcinoma

Interventions: PI-88, Placebo

Sponsor: Cellxpert Biotechnology Corp. | Started: 2011-08

Phase III Study of PI-88 in Post-resection Hepatocellular Carcinoma Terminated

PHASE3 NCT00568308 n=600

Cancer, Liver Cancer, Primary Liver Cancer

Interventions: PI-88, placebo

Sponsor: Progen Pharmaceuticals | Started: 2007-12

Linked Hypotheses (2)

Glycosaminoglycan Template Disruption Approach0.649

Glial Glycocalyx Remodeling Therapy0.649

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

associated with (1)

HSPG2 → neurodegeneration

co discussed (8)

HSPG2 → P2RY12

HSPG2 → P2RX7

HSPG2 → EPHB4

...and 3 more

interacts with (8)

NCSTN → HSPG2

APH1B → HSPG2

...and 3 more

regulates (3)

HSPG2 → IGF1R

Debate History (0)

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