HK2

Hexokinase 2

Score: 0.624 Price: $0.62 Low Druggability Status: active Wiki: HK2

🧠 Neurodegeneration

HYPOTHESES

5

PAPERS

54

KG EDGES

453

DEBATES

0

3D Protein Structure

🧬 HK2 — PDB 2NZT Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.38

Clinical Stage

Phase III

Target Class

Enzyme

Safety

0.30

Druggability Analysis

Drug Development0.45

Structural Tractability0.70

Target Class0.85

Safety Profile0.30

Key Metrics

PDB Structures:

4

Known Drugs:

1

Approved:

0

In Clinical Trials:

0

Drug Pipeline (1 compounds)

Therapeutic Areas:

Neurodegenerative diseases (Alzheimer's, Parkinson's) Cancer metabolism Neuroinflammation Mitochondrial dysfunction disorders Metabolic neurological disorders

Druggability Rationale: HK2 is highly druggable (0.75 score) due to its well-characterized enzymatic active site with available crystal structures at high resolution (2.45 Å), established precedent with 2-Deoxyglucose in clinical trials, and the fact that enzymes with defined catalytic pockets are proven drug targets. The abundance of structural data (4 PDB entries plus AlphaFold model) provides excellent opportunities for rational drug design and structure-based optimization.

Mechanism: Small molecule inhibitor of glucose phosphorylation

Drug Pipeline (1 compounds)

Known Drugs:

2-Deoxyglucose (Investigational) — Cancer

Structural Data:

PDB (4) ✓AlphaFold ✓Cryo-EM —

2NZT 5HEX 5HFU 5HG1

UniProt: Q53QX9

Binding Pocket Analysis:

The HK2 active site accommodates glucose and ATP substrates, with structural data revealing a well-defined nucleotide-binding pocket and glucose-binding cleft characteristic of the hexokinase family. The available crystal structures enable structure-activity relationship studies to design selective inhibitors that occupy the ATP or glucose-binding regions while potentially exploiting allosteric sites unique to HK2.

🧬 3D Protein Structure

🧬 HK2 — PDB 2NZT Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

A key selectivity challenge is differentiating HK2 inhibition from other hexokinase isoforms (HK1, HK3, HK4/glucokinase), as off-target inhibition could disrupt systemic glucose metabolism. However, HK2's preferential mitochondrial localization and tissue distribution (high in brain, muscle, heart) may enable selective targeting through structural features or subcellular delivery strategies.

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 (10)

Relevant trials from ClinicalTrials.gov

Active

5

Completed

2

Total Enrollment

1,433

By Phase

EARLY_PHASE1: 2 · NA: 2 · PHASE1: 3 · PHASE2: 1 · PHASE3: 1 · Unknown: 1

A Study of JNJ-69086420, an Actinium-225-Labeled Antibody Targeting Human Kallikrein-2 (hK2) for Advanced Prostate Cance Active Not Recruiting

PHASE1 NCT04644770 n=144

Prostatic Neoplasms, Adenocarcinoma

Interventions: JNJ-69086420, JNJ-78278343, Stereotactic body radiation therapy

Sponsor: Janssen Research & Development, LLC | Started: 2020-11-12

A Study of Pasritamig Versus Placebo in Late Line Metastatic Castration-resistant Prostate Cancer (mCRPC) Recruiting

PHASE3 NCT07164443 n=663

Metastatic Castration-resistant Prostate

Interventions: Pasritamig, Placebo, Best Supportive Care (BSC)

Sponsor: Janssen Research & Development, LLC | Started: 2025-09-02

Evaluation of Molecular Forms of PSA and Human Kallikrein 2 in a Cohort of Patients With Locally Resected Prostate Cance Completed

Unknown NCT02070575 n=200

Prostate Cancer

Interventions: blood draw

Sponsor: Memorial Sloan Kettering Cancer Center | Started: 2014-02-20

Neuro-pharmacological Properties of Repurposed Posaconazole in Glioblastoma: A Phase 0 Clinical Trial Terminated

EARLY_PHASE1 NCT04825275 n=7

Glioblastoma, Glioblastoma Multiforme, Glioblastoma Multiforme of Brain

Interventions: Posaconazole Pill

Sponsor: Milton S. Hershey Medical Center | Started: 2022-05-13

Effect of Short-chain Fatty Acids on Aerobic Endurance Completed

NA NCT06054607 n=21

Aerobic Endurance, Metabolism

Interventions: High-amylose maize starch+acetate/butyra, Low-amylose maize starch

Sponsor: United States Army Research Institute of Environmental Medic | Started: 2023-07-21

A Study of JNJ-78278343 in Combination With JNJ-95298177 for Treatment of Prostate Cancer Recruiting

PHASE1 NCT07082920 n=140

Prostatic Neoplasms

Interventions: JNJ-78278343, JNJ-95298177

Sponsor: Janssen Research & Development, LLC | Started: 2025-07-07

A Study of JNJ-78278343, a T-Cell-Redirecting Agent Targeting Human Kallikrein 2 (KLK2), for Advanced Prostate Cancer Active Not Recruiting

PHASE1 NCT04898634 n=216

Prostatic Neoplasms

Interventions: JNJ-78278343

Sponsor: Janssen Research & Development, LLC | Started: 2021-07-13

Safety and Targeting of Anti-hk2 Antibody in mCRPC Terminated

EARLY_PHASE1 NCT04116164 n=27

Castration-Resistant Prostatic Cancer, Metastatic Disease

Interventions: 111In-DOTA-h11B6

Sponsor: SpectronRX | Started: 2019-09-18

Linked Hypotheses (2)

Metabolic Switch Targeting for A1→A2 Repolarization0.481

Metabolic Reprogramming via Microglial Glycolysis Inhibition0.385

Linked Experiments (1)

Proposed experiment from debate on Astrocytes adopt A1 (neurotoxic) and A2 (neuroprotective) phenoty0.400

Scoring Dimensions

Knowledge Graph (20)

activates (4)

associated with (1)

HK2 → neurodegeneration

co discussed (15)

...and 10 more

Debate History (0)

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