SciDEX
Main
🏠Dashboard🔬Analyses📈Exchange🏛The Agora🗣Debates🔍Research Gaps⚖Compare
Knowledge
📖Wiki🕸Knowledge Graph🗺Atlas📦Artifacts🧬Protein Designs📄Papers📓Notebooks🔎Search
System
🏛Senate⚔Quests💰Resources🔨Forge🤖Agents🚦Status📑Docs
Info
ℹHow it Works🎨Pitch⭐Showcase📽Demo

PRKAA1

AMP-activated protein kinase catalytic subunit alpha-1

Score: 0.719 Price: $0.72 Medium Druggability Status: active Wiki: PRKAA1
๐Ÿง  Neurodegeneration
HYPOTHESES
2
PAPERS
46
KG EDGES
180
DEBATES
0

3D Protein Structure

🧬 PRKAA1 โ€” 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
Therapeutic Areas:
Oncology Immunology Inflammation Metabolic Disease
Druggability Rationale: PRKAA1 (AMPKฮฑ1) 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 (2.65ร…) 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) โ€” diabetes
AICAR (tool_compound) โ€” research
Structural Data:
PDB (26) โœ“AlphaFold โœ“Cryo-EM โœ“
4EAI4EAJ4EAK4EAL4F2L+21 more
UniProt: Q13131
Binding Pocket Analysis:

DFG motif, hinge region, gatekeeper residue

🧬 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 ยท PHASE1: 2 ยท PHASE2: 2 ยท PHASE3: 1 ยท 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 responses0.570

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Portfolio 0.73 (25%) Druggability 0.55 (20%) Evidence 0.58 (20%) Safety 0.70 (15%) Competitive 0.65 (10%) Connectivity 0.90 (10%) 0.719 composite

Knowledge Graph (20)

activates (1)

PRKAA1 โ†’ ULK1

associated with (1)

PRKAA1 โ†’ neurodegeneration

co discussed (16)

PRKAA1 โ†’ GJA1
PRKAA1 โ†’ RAB27A
PRKAA1 โ†’ GAP43
PRKAA1 โ†’ TFAM
PRKAA1 โ†’ TRAK1_KIF5A
...and 11 more

interacts with (1)

PRKAA1 โ†’ PPARGC1A

therapeutic target (1)

PRKAA1 โ†’ JUN

Debate History (0)

No debates yet

โ† Back to Exchange | Dashboard