DNAJB1

DnaJ heat shock protein family (Hsp40) member B1

Score: 0.524 Price: $0.52 Low Druggability Status: active Wiki: DNAJB1

🧠 Neurodegeneration

HYPOTHESES

3

PAPERS

14

KG EDGES

113

DEBATES

1

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:

14

Known Drugs:

2

Approved:

0

In Clinical Trials:

0

Drug Pipeline (2 compounds)

2 Preclinical

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

🧬 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.

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 (5)

Relevant trials from ClinicalTrials.gov

Active

5

Completed

0

Total Enrollment

204

By Phase

PHASE1: 5

FusionVAC22_01: Fusion Transcript-based Peptide Vaccine Combined with Immune Checkpoint Inhibition Recruiting

PHASE1 NCT05937295 n=20

Fibrolamellar Hepatocellular Carcinoma

Interventions: Fusion-VAC-XS15

Sponsor: University Hospital Tuebingen | Started: 2023-09-26

Testing the Addition of an Anti-cancer Drug, DT2216, to the Usual Chemotherapy Treatment for Relapsed or Refractory Soli Recruiting

PHASE1 NCT06620302 n=81

Childhood Fibrolamellar Carcinoma, Recurrent Childhood Fibrolamellar Carcin, Recurrent Childhood Malignant Solid Neop

Interventions: Bcl-XL Proteolysis Targeting Chimera DT2, Biospecimen Collection, Irinotecan

Sponsor: Children's Oncology Group | Started: 2025-06-12

A DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Glutamine Antagonist DRP-104, Nivolumab, and Ipilimumab in P Not Yet Recruiting

PHASE1 NCT07430202 n=27

Liver Cancer (Fibrolamellar Hepatocellul

Interventions: DNAJB1-PRKACA Peptide Vaccine, DRP-104, Nivolumab

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Started: 2026-05

Peptide Vaccine for Fibrolamellar Hepatocellular Carcinoma Patients and Other Tumor Entities Carrying the Driver Fusion Recruiting

PHASE1 NCT06789198 n=20

Fibrolamellar Hepatocellular Carcinoma (

Interventions: Vaccination of Fusion-VAC-XS15

Sponsor: University Hospital Tuebingen | Started: 2025-07-08

DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Fibrolamellar Hepat Recruiting

PHASE1 NCT04248569 n=56

Fibrolamellar Hepatocellular Carcinoma (

Interventions: DNAJB1-PRKACA peptide vaccine, Nivolumab, Ipilimumab

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Started: 2020-04-20

Linked Hypotheses (0)

No linked hypotheses

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

associated with (1)

DNAJB1→neurodegeneration

co discussed (6)

APOE→DNAJB1DNAJB1→ST6GAL1DNAJB1→FUT8HSPA1A→DNAJB1DNAJB1→HSP90AA1

▸ Show 1 more

interacts with (6)

HSPA1A→DNAJB1HSP90AA1→DNAJB1DNAJB1→HSPA1ADNAJB1→HSP90AA1DNAJB1→FKBP5

▸ Show 1 more

protects against (1)

DNAJB1→mutant Huntingtin aggregation

regulates (5)

CD4→DNAJB1HSPA1A→DNAJB1SCA3→DNAJB1HSPA4→DNAJB1FOXP1→DNAJB1

therapeutic target (1)

DNAJA2→DNAJB1

Debate History (1)

Should DNAJB1 (DnaJ heat shock protein family (Hsp40) member B1) be prioritized 2026-04-22