AADC

Aromatic L-amino acid decarboxylase

Score: 0.384 Price: $0.38 Medium Druggability Status: active Wiki: AADC

🧠 Neurodegeneration

HYPOTHESES

1

PAPERS

0

KG EDGES

9

DEBATES

1

3D Protein Structure

🧬 AADC — PDB 1JS3 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.50

Clinical Stage

Approved

Target Class

Enzyme

Safety

0.40

Druggability Analysis

Drug Development0.75

Structural Tractability0.70

Target Class0.85

Safety Profile0.40

Key Metrics

PDB Structures:

3

Known Drugs:

1

Approved:

1

In Clinical Trials:

0

Drug Pipeline (1 compounds)

1 Approved

Druggability Rationale: AADC is highly druggable (0.90 score) due to its well-defined catalytic active site, proven clinical validation by approved drug carbidopa, and extensive structural characterization with 3 PDB structures at 1.7 Å resolution. The enzyme's established role in Parkinson's disease therapy and availability of high-quality structural data enable rational drug design of competitive inhibitors targeting the pyridoxal-5'-phosphate (PLP) cofactor binding pocket.

Mechanism: Small molecule inhibitor preventing peripheral conversion of levodopa to dopamine

Drug Pipeline (1 compounds)

1 Approved

Known Drugs:

Carbidopa (approved) — Parkinson's disease (with levodopa)

Structural Data:

PDB (3) ✓AlphaFold ✓Cryo-EM —

UniProt: A0A3Q8A018

🧬 3D Protein Structure

🧬 AADC — PDB 1JS3 Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

Peripheral selectivity is the critical challenge—drugs must inhibit AADC in the periphery while minimizing CNS penetration to avoid reducing central dopamine synthesis. AADC has limited isoforms, reducing isoform selectivity complexity, but off-target inhibition of other PLP-dependent enzymes (e.g., DOPA decarboxylase variants, monoamine oxidases) must be carefully evaluated to prevent adverse metabolic 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

1

Completed

7

Total Enrollment

531

By Phase

PHASE1: 3 · PHASE2: 2 · PHASE3: 2 · PHASE4: 1

Efficacy, Safety and Tolerability Study of ND0612 vs. Oral Immediate Release Levodopa/Carbidopa (IR-LD/CD) in Subjects W Active Not Recruiting

PHASE3 NCT04006210 n=381

Parkinson's Disease

Interventions: ND0612 Solution for SC infusion, Placebo for SC infusion, Oral IR-LD/CD

Sponsor: NeuroDerm Ltd. | Started: 2019-09-30

Norepinephrine-targeted Therapy for Action Control in Parkinson Disease Completed

PHASE4 NCT03115827 n=15

Parkinson Disease

Interventions: Droxidopa, Carbidopa

Sponsor: Vanderbilt University Medical Center | Started: 2017-04-18

Carbidopa-Levodopa (CD-LD) ER Alone or in Combination With CD-LD IR to IPX066 Followed by IPX066 Extension Safety Study Completed

PHASE3 NCT01411137 n=43

Parkinson's Disease

Interventions: IPX066

Sponsor: Impax Laboratories, LLC | Started: 2011-08

A Study to Investigate the Tolerability and Effect of Three Single-dose Regimens of BIA 9-1067 Completed

PHASE2 NCT01568034 n=10

Parkinson's Disease

Interventions: BIA 9-1067, BIA 9-1067, BIA 9-1067

Sponsor: Bial - Portela C S.A. | Started: 2009-04

Multicentre Study in Four Parallel Groups of Parkinson's Disease (PD) Patients Completed

PHASE2 NCT01568047 n=40

Parkinson's Disease

Interventions: Placebo, BIA 9-1067, BIA 9-1067

Sponsor: Bial - Portela C S.A. | Started: 2010-02

A Study of AAV-hAADC-2 in Subjects With Parkinson's Disease Completed

PHASE1 NCT00229736 n=10

Parkinson's Disease

Interventions: AAV-hAADC-2, AAV-hAADC-2

Sponsor: Genzyme, a Sanofi Company | Started: 2004-11

Safety and Efficacy Study of VY-AADC01 for Advanced Parkinson's Disease Completed

PHASE1 NCT03065192 n=16

Idiopathic Parkinson's Disease, Parkinson's Disease, Basal Ganglia Disease

Interventions: VY-AADC01

Sponsor: Neurocrine Biosciences | Started: 2017-05-11

A Study of the Pharmacokinetics, Pharmacodynamics, and Safety of Opicapone in Subjects With Parkinson's Disease Taking L Completed

PHASE1 NCT03496870 n=16

Parkinson Disease

Interventions: Opicapone, Carbidopa Levodopa

Sponsor: Neurocrine Biosciences | Started: 2018-02-08

Linked Hypotheses (0)

No linked hypotheses

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

associated with (1)

AADC→neurodegeneration

co discussed (14)

ALOX15→AADCAADC→CMKLR1LRP1→AADCAADC→AQP4CMKLR1→AADC

▸ Show 9 more

AADC→GFAPAADC→ALOX15AQP4→AADCAADC→LRP1AADC→TLR4CLDN1→AADCHSPA1A→AADCAHR→AADCDNMT1→AADC

implicated in (1)

AADC→neurodegeneration

interacts with (2)

TH→AADCAADC→TH

participates in (1)

AADC→Tyrosine hydroxylase / catecholamine synthesis

targets (1)

h-7bb47d7a→AADC

Debate History (1)

Should AADC (Aromatic L-amino acid decarboxylase) be prioritized as a therapeuti2026-04-22