PRKAA1

AMP-activated protein kinase catalytic subunit alpha-1

Score: 0.669 Price: $0.67 Medium Druggability Status: active Wiki: PRKAA1

🧠 Neurodegeneration

HYPOTHESES

2

PAPERS

46

KG EDGES

180

DEBATES

1

3D Protein Structure

🧬 PRKAA1 — PDB 4CFH Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.55

Clinical Stage

Approved

Target Class

Kinase

Safety

0.70

Druggability Analysis

Drug Development0.75

Structural Tractability0.85

Target Class0.85

Safety Profile0.70

Key Metrics

PDB Structures:

26

Known Drugs:

2

Approved:

1

In Clinical Trials:

0

Drug Pipeline (2 compounds)

1 Approved

Druggability Rationale: PRKAA1 (AMPKα1) represents a highly druggable kinase target with established small molecule modulation potential, evidenced by metformin's approved mechanism of indirect AMPK activation. The extensive structural data, including multiple PDB entries and AlphaFold predictions, suggests high potential for precise molecular targeting, particularly given AMPK's critical role in cellular energy metabolism and neuroprotective signaling pathways. The existing tool compounds and structural resolution (2.65Å) provide a strong foundation for rational drug design targeting neurodegeneration.

Mechanism: Small molecule activator of AMP-activated protein kinase

Drug Pipeline (2 compounds)

1 Approved

Known Drugs:

Metformin (approved) — diabetes

AICAR (tool_compound) — research

Structural Data:

PDB (26) ✓AlphaFold ✓Cryo-EM ✓

4EAI 4EAJ 4EAK 4EAL 4F2L+21 more

UniProt: Q13131

🧬 3D Protein Structure

🧬 PRKAA1 — PDB 4CFH Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

Kinase selectivity is critical due to the ~518 kinases in the human kinome. Off-target kinase inhibition can cause toxicities including cardiotoxicity, hepatotoxicity, and skin reactions. Selectivity profiling against a kinase panel (e.g., DiscoverX scanMAX) is essential.

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

8

Total Enrollment

1,140

By Phase

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

Effect of Farxiga on Renal Function and Size in Type 2 Diabetic Patients With Hyperfiltration Completed

PHASE4 NCT02911792 n=72

Diabetes Mellitus, Type 2

Interventions: Dapagliflozin, Metformin, Glipizide 5 MG

Sponsor: The University of Texas Health Science Center at San Antonio | Started: 2016-12-20

Study to Compare the Efficacy and Safety of Administration of the Fix Dose Combination of Linagliptin Plus Metformin in Completed

PHASE3 NCT01708902 n=876

Diabetes Mellitus, Type 2

Interventions: linagliptin2.5mg/metformin1000mg, linagliptin2.5mg/metformin1000mg, linagliptin 5mg

Sponsor: Boehringer Ingelheim | Started: 2012-10

A Study Investigating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2330672 Administered With Metfor Completed

PHASE2 NCT02202161 n=70

Diabetes Mellitus, Type 2

Interventions: GSK2330672, Placebo, Sitagliptin

Sponsor: GlaxoSmithKline | Started: 2014-08-27

Phase II Pilot Study of Aminoimidazole Carboxamide Riboside (AICAR), a Precursor of Purine Synthesis, for Lesch-Nyhan Di Completed

PHASE2 NCT00004314 n=2

Lesch-Nyhan Syndrome

Interventions: aminomidazole carboxamide riboside

Sponsor: National Center for Research Resources (NCRR) | Started: 1996-02

Phase I/II Study OF Metformin in Combination With Cisplatin and Radiation in Head and Neck Squamous Cell Carcinoma Completed

PHASE1 NCT02949700 n=26

Head and Neck Squamous Cell Carcinoma

Interventions: Metformin

Sponsor: Baylor College of Medicine | Started: 2017-01-26

Bioequivalence Study for Acarbose/Metformin FDC Completed

PHASE1 NCT04065581 n=24

Diabetes Mellitus, Type 2

Interventions: Acarbose/Metformin FDC(BAY81-9783), Glucobay, Glucophage

Sponsor: Bayer | Started: 2019-10-14

Investigatory Study of Metformin's Pharmacokinetics, Pharmacodynamics and Drug Drug Interactions Classifying the Group b Completed

NA NCT01274130 n=30

Healthy Adult

Interventions: Metformin

Sponsor: Yonsei University | Started: 2010-12

Contraction (Exercise) Mediated Glucose Uptake as a Therapeutic Target in Type 2 Diabetes Completed

NA NCT00168519 n=40

Diabetes Mellitus, Type 2

Interventions: nitroprusside, pentalong, imdur, AICAR,

Sponsor: Baker Heart Research Institute | Started: 2002-10

Linked Hypotheses (1)

AMPK hypersensitivity in astrocytes creates enhanced mitochondrial rescue responses0.813

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

associated with (1)

PRKAA1→neurodegeneration

co discussed (17)

COX4I1→PRKAA1PRKAA1→GJA1PRKAA1→RAB27APRKAA1→GAP43PRKAA1→TFAM

▸ Show 12 more

PRKAA1→TRAK1_KIF5AFOXP3→PRKAA1TNFA→PRKAA1PRKAA1→NR3C1PRKAA1→DRD2PRKAA1→CHR2PRKAA1→CLOCKPRKAA1→CRHPRKAA1→BDNFPRKAA1→SNCAPRKAA1→ANGPT1PRKAA1→ULK1

interacts with (2)

PPARGC1A→PRKAA1PRKAA1→PPARGC1A

Debate History (1)

Should PRKAA1 (AMP-activated protein kinase catalytic subunit alpha-1) be priori2026-04-21