SRPK1

SRSF protein kinase 1

Score: 0.630 Price: $0.63 Low Druggability Status: active Wiki: SRPK1

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

DEBATES

3D Protein Structure

🧬 SRPK1 — PDB 1WAK Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.40

Clinical Stage

Phase II

Target Class

Kinase

Safety

0.50

Druggability Analysis

Drug Development0.30

Structural Tractability0.70

Target Class0.85

Safety Profile0.50

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (1 compounds)

1 Preclinical

Therapeutic Areas:

Neurodegeneration (tau pathology, Alzheimer's disease) Frontotemporal dementia ALS (amyotrophic lateral sclerosis) Oncology (cancer with splicing dysregulation) Neuroinflammation

Druggability Rationale: SRPK1 represents a promising druggable target for neurodegeneration due to its critical role in regulating alternative splicing of tau and other neurologically relevant proteins, with SPHINX31 demonstrating preclinical potential to modulate aberrant splicing mechanisms. The availability of high-resolution structural data (including PDB entries and AlphaFold predictions) and the kinase classification suggest tractable opportunities for developing selective small molecule inhibitors that could interrupt pathogenic protein misprocessing in neurodegenerative conditions.

Mechanism: SRPK1 inhibitors block phosphorylation of serine/arginine-rich splicing factors, modulating alternative splicing patterns implicated in neurodegeneration and cancer. By preventing aberrant splicing, these inhibitors can restore normal protein isoform expression and reduce pathogenic tau accumulation.

Drug Pipeline (1 compounds)

1 Preclinical

Known Drugs:

SPHINX31 (preclinical) — Cancer research

Structural Data:

PDB (6) ✓AlphaFold ✓Cryo-EM —

3BEG 4WUA 5MY8 6FAD 7DD1+1 more

UniProt: H3BLV9

Binding Pocket Analysis:

SRPK1 possesses a canonical ATP-binding pocket in the kinase domain amenable to type I/II inhibitor design, as evidenced by the six PDB structures (3BEG, 4WUA, 5MY8, 6FAD, 7DD1, and supporting structures). The high-resolution structures (1.2 Å) reveal detailed binding pocket topology suitable for structure-based drug design and structure-activity relationship optimization.

🧬 3D Protein Structure

🧬 SRPK1 — PDB 1WAK Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

SRPK1 selectivity against other SRSF kinases (CLK family) and broader kinome represents a key challenge; however, SRPK1's unique substrate specificity toward serine/arginine-rich proteins offers potential for selective targeting. Off-target effects on related splicing kinases could complicate therapeutic window and require isoform-selective inhibitor design.