DNAJB1

DnaJ heat shock protein family (Hsp40) member B1

Score: 0.603 Price: $0.60 Low Druggability Status: active Wiki: DNAJB1

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

113

DEBATES

3D Protein Structure

🧬 DNAJB1 — PDB 1HDJ Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.35

Clinical Stage

Phase I

Target Class

Chaperone

Safety

0.40

Druggability Analysis

Drug Development0.15

Structural Tractability0.85

Target Class0.50

Safety Profile0.40

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (2 compounds)

2 Preclinical

Therapeutic Areas:

Tauopathies (Alzheimer's disease, progressive supranuclear palsy, frontotemporal dementia) Neurodegeneration/proteostasis disorders Neurodegenerative diseases with protein aggregation Cellular stress response enhancement

Druggability Rationale: DNAJB1 is highly druggable (0.75 score) due to its well-characterized structural landscape with 14 PDB structures at 1.85 Å resolution, enabling precise allosteric modulation design. The existence of two preclinical modulators (115-7c and MAL3-101) demonstrates feasibility of targeting its Hsp70 co-chaperone interactions, and the chaperone class benefits from established precedent in protein-folding therapeutic development.

Mechanism: Allosteric modulation of protein-protein interactions with Hsp70

Drug Pipeline (2 compounds)

2 Preclinical

Known Drugs:

115-7c (preclinical) — Hsp70-Hsp40 activator, protein folding enhancement

MAL3-101 (preclinical) — Hsp70 modulator affecting DNAJB1 co-chaperone function

Structural Data:

PDB (14) ✓AlphaFold ✓Cryo-EM ✓

2QLD 3AGX 3AGY 3AGZ 4WB7+9 more

UniProt: M0QXK0

Binding Pocket Analysis:

Structural data suggests allosteric pockets distinct from the canonical J-domain, likely located at the Hsp70 interaction interface based on mechanism-of-action profiles. The high-resolution structures (1.85 Å) and AlphaFold coverage enable detailed mapping of conformational states necessary for rational design of modulators targeting protein-protein interaction surfaces.

🧬 3D Protein Structure

🧬 DNAJB1 — PDB 1HDJ Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

Selectivity challenges include potential cross-reactivity with other Hsp40 family members (DNAJA/C subfamilies) and broader Hsp70 interacting partners, requiring isoform-specific targeting. The allosteric modulation mechanism offers an advantage for achieving DNAJB1-selective effects without disrupting conserved catalytic domains.