TH

Tyrosine hydroxylase

Score: 0.727 Price: $0.73 Medium Druggability Status: active Wiki: TH

🧠 Neurodegeneration

HYPOTHESES

157

PAPERS

0

KG EDGES

11328

DEBATES

0

3D Protein Structure

🧬 TH — PDB 1TOH Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.54

Clinical Stage

Approved

Target Class

Enzyme

Safety

0.40

Druggability Analysis

Drug Development0.90

Structural Tractability0.70

Target Class0.85

Safety Profile0.40

Key Metrics

PDB Structures:

8

Known Drugs:

2

Approved:

2

In Clinical Trials:

0

Drug Pipeline (2 compounds)

2 Approved

Therapeutic Areas:

Parkinson's disease L-DOPA-responsive dystonia (DRD) Dopamine deficiency syndromes Movement disorders Neurodegeneration - dopaminergic dysfunction

Druggability Rationale: TH is highly druggable (0.90 score) as an enzyme target with well-defined catalytic mechanisms and extensive structural characterization (8 PDB structures at 2.68 Å resolution). The established clinical success of L-DOPA and carbidopa demonstrates validated therapeutic pathways, though direct TH inhibition is contraindicated; instead, downstream dopamine replacement circumvents reduced TH activity in Parkinson's disease.

Mechanism: Enzyme replacement therapy via L-DOPA supplementation to bypass reduced TH activity

Drug Pipeline (2 compounds)

2 Approved

Known Drugs:

L-DOPA (approved) — Parkinson's disease

Carbidopa (approved) — Parkinson's disease (combination with L-DOPA)

Structural Data:

PDB (8) ✓AlphaFold ✓Cryo-EM ✓

1SDZ 1SE0 2MDA 6ZN2 6ZVP+3 more

UniProt: E7EQI0

Binding Pocket Analysis:

TH possesses a well-characterized pterin-dependent catalytic site with substrate (L-tyrosine) and cofactor (tetrahydrofolate) binding pockets; structural data reveals allosteric regulatory sites sensitive to dopamine feedback inhibition. The active site architecture and cofactor requirements provide multiple druggable intervention points for competitive and allosteric modulators.

🧬 3D Protein Structure

🧬 TH — PDB 1TOH Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

TH exists as multiple tissue-specific isoforms with varying regulatory properties; selectivity challenges include avoiding off-target inhibition of phenylalanine hydroxylase (PAH) and tryptophan hydroxylase (TPH), which share structural homology. Isoform-selective modulation could optimize CNS dopamine production while minimizing peripheral effects.

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

7

Completed

1

Total Enrollment

3,819

By Phase

NA: 3 · PHASE1: 1 · PHASE3: 3 · PHASE4: 1

A Study to Compare Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab (MK-3475) Versus Pembrolizumab Al Recruiting

PHASE3 NCT06952504 n=1123

Endometrial Cancer

Interventions: Pembrolizumab, Carboplatin, Paclitaxel

Sponsor: Merck Sharp & Dohme LLC | Started: 2025-05-22

Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab Versus Pembrolizumab Alone in Metastatic Non-small C Recruiting

PHASE3 NCT06170788 n=614

Non-small Cell Lung Cancer (NSCLC)

Interventions: Sacituzumab tirumotecan, Pembrolizumab, Supportive care measures

Sponsor: Merck Sharp & Dohme LLC | Started: 2023-12-15

DemensiaKITA Mobile Health App to Improve Knowledge, Attitude, Practice and Reduce Burden Among Dementia Caregivers in M Recruiting

NA NCT07212894 n=451

Dementia

Interventions: DemensiaKITA mobile health application, Usual Care

Sponsor: Universiti Teknologi Mara | Started: 2025-10-10

Moderate Versus High Volume Light-Moderate Intensity Exercise for People With Moderate Parkinson's Disease Recruiting

NA NCT06088355 n=123

Parkinson Disease, Movement Disorders, Neurodegeneration

Interventions: HV-PDAE: High Volume Partnered Dance Aer, MV-PDAE: Moderate Volume Partnered Dance, MV-WALK: Moderate Volume Walking

Sponsor: VA Office of Research and Development | Started: 2025-01-25

AV-1980R (Tau Vaccine) in Preclinical Alzheimer's Disease (TAURUS-1980) Not Yet Recruiting

PHASE1 NCT07158905 n=48

Alzheimer Disease, Preclinical Alzheimer's Disease

Interventions: AV-1980R 20 µg, AV-1980R 60 µg, AV-1980R 180 µg

Sponsor: Institute for Molecular Medicine | Started: 2025-12-15

Study of Pembrolizumab With Concurrent Chemoradiation Therapy Followed by Pembrolizumab With or Without Olaparib in Stag Active Not Recruiting

PHASE3 NCT04380636 n=870

Lung Neoplasms, Carcinoma, Non-Small-Cell Lung

Interventions: Pembrolizumab, Olaparib, Placebo for olaparib

Sponsor: Merck Sharp & Dohme LLC | Started: 2020-07-06

Physical Activity and Disability Prevention in Postmenopausal Women Active Not Recruiting

NA NCT06781541 n=72

Metabolic Syndrome, Fall Risk, Sarcopenia in Elderly

Interventions: Nordic walking, Strength training, Bungy Pump Exercises

Sponsor: Gdansk University of Physical Education and Sport | Started: 2022-02-21

Efficacy and Safety of Opicapone in Clinical Practice Completed

PHASE4 NCT02847442 n=518

Parkinson's Disease With Wearing-of

Interventions: BIA 9-1067, levodopa/dopa decarboxylase inhibitor

Sponsor: Bial - Portela C S.A. | Started: 2016-11-23

Linked Hypotheses (0)

No linked hypotheses

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

associated with (3)

TH → neurodegeneration

co discussed (12)

TH → TNF

...and 7 more

implicated in (1)

TH → neurodegeneration

interacts with (1)

participates in (1)

TH → Tyrosine hydroxylase / catecholamine synthesis

regulates (2)

TH → TNF

TH → UBIQUITIN

Debate History (0)

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