HSPA1A

Heat Shock Protein Family A Member 1A

Score: 0.615 Price: $0.61 Medium Druggability Status: active Wiki: HSPA1A

🧠 Neurodegeneration

HYPOTHESES

3

PAPERS

46

KG EDGES

632

DEBATES

1

3D Protein Structure

🧬 HSPA1A — PDB 3GDQ Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.46

Clinical Stage

Phase III

Target Class

Chaperone

Safety

0.60

Druggability Analysis

Drug Development0.55

Structural Tractability0.95

Target Class0.50

Safety Profile0.60

Key Metrics

PDB Structures:

60

Known Drugs:

3

Approved:

0

In Clinical Trials:

2

Drug Pipeline (3 compounds)

2 Phase III · 1 Preclinical

Druggability Rationale: HSPA1A demonstrates medium druggability (0.60) supported by 60 PDB structures with excellent resolution (1.34 Å), multiple phase 3 clinical candidates (17-AAG, Ganetespib), and a well-characterized ATP-binding pocket. However, the challenge lies in achieving selective modulation of chaperone function without triggering unwanted stress responses, and the target's highly conserved nature across HSP70 family members complicates isoform selectivity.

Mechanism: Small molecule activators or allosteric modulators of chaperone function

Drug Pipeline (3 compounds)

2 Phase III · 1 Preclinical

Known Drugs:

17-AAG (phase_3) — cancer

Ganetespib (phase_3) — cancer

VER-155008 (research_tool) — cancer research

Structural Data:

PDB (60) ✓AlphaFold ✓Cryo-EM ✓

1S3X 2LMG 3ATU 3ATV 3AY9+55 more

UniProt: V9GZ37

🧬 3D Protein Structure

🧬 HSPA1A — PDB 3GDQ Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

Selectivity remains a significant challenge due to high sequence homology among HSP70 isoforms (HSPA1A, HSPA1B, HSPA2); off-target engagement with other heat shock proteins and potential immune activation through stress response pathways must be carefully managed. Allosteric modulation strategies may offer better selectivity than direct ATP-site inhibitors.

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 (6)

Relevant trials from ClinicalTrials.gov

Active

0

Completed

5

Total Enrollment

121

By Phase

PHASE1: 4 · PHASE2: 2

An Open-Label Multicenter Phase 2 Window of Opportunity Study Evaluating Ganetespib in Women With Breast Cancer Completed

PHASE2 NCT01677455 n=51

Breast Cancer, HER-2 Positive Breast Cancer, Triple Negative Breast Cancer

Interventions: ganetespib

Sponsor: Synta Pharmaceuticals Corp. | Started: 2012-07

A Study Evaluating STA-9090 in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor (GIST) Completed

PHASE2 NCT01039519 n=27

Gastrointestinal Stromal Tumor

Interventions: Ganetespib

Sponsor: Synta Pharmaceuticals Corp. | Started: 2010-01

Ganetespib, Paclitaxel, Trastuzumab and Pertuzumab for Metastatic Human Epidermal Growth Factor Receptor 2 Positive Brea Completed

PHASE1 NCT02060253 n=9

HER2-positive Breast Cancer, Male Breast Cancer, Recurrent Breast Cancer

Interventions: ganetespib, paclitaxel, trastuzumab

Sponsor: Memorial Sloan Kettering Cancer Center | Started: 2014-04

Phase I Trial of Ganetespib, Capecitabine, and Radiation in Rectal Cancer Completed

PHASE1 NCT01554969 n=16

Rectal Cancer

Interventions: capecitabine + ganetespib

Sponsor: Emory University | Started: 2012-05

Crizotinib and Ganetespib (STA-9090) in ALK Positive Lung Cancers Completed

PHASE1 NCT01579994 n=13

Advanced Lung Cancer

Interventions: Ganetespib (STA-9090) and crizotinib

Sponsor: Memorial Sloan Kettering Cancer Center | Started: 2012-04-16

Ganetespib and Ziv-Aflibercept in Refractory Gastrointestinal Carcinomas, Non-Squamous Non-Small Cell Lung Carcinomas, U Terminated

PHASE1 NCT02192541 n=5

Neoplasms

Interventions: Ziv-Aflibercept, Ganetespib

Sponsor: National Cancer Institute (NCI) | Started: 2014-12-02

Linked Hypotheses (7)

Proteostasis Enhancement via APOE Chaperone Targeting0.724

Heat Shock Protein 70 Disaggregase Amplification0.625

Hsp70-based therapy to prevent lysosomal membrane permeabilization and cathepsin release in AD0.570

Tau Conformation-Selective HSP70 Inhibition0.455

Co-chaperone Hijacking Strategy0.455

Chaperone Network Reprogramming Therapy0.455

Temporal Gating Through HSP70 ATPase Cycle Manipulation0.455

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

associated with (1)

HSPA1A→neurodegeneration

co discussed (9)

TGM2→HSPA1APRMT1→HSPA1APARP1→HSPA1AHSPA1A→G3BP1HSPA1A→SRPK1

▸ Show 4 more

TARDBP→HSPA1AAPOE→HSPA1AHSPA1A→DNAJB1HSPA1A→HSP90AA1

interacts with (10)

HSPA1A→HSP90AA1HSPA1A→DNAJB1HSPA1A→FKBP5HSP90AA1→HSPA1ADNAJB1→HSPA1A

▸ Show 5 more

FKBP5→HSPA1ASNCA→HSPA1AHSPA1A→SNCAHSPA1A→DNMT1DNMT1→HSPA1A

Debate History (1)

Should HSPA1A (Heat Shock Protein Family A Member 1A) be prioritized as a therap2026-04-21