HSP90AA1

Heat Shock Protein 90 Alpha Family Class A Member 1

Score: 0.633 Price: $0.63 Low Druggability Status: active Wiki: HSP90AA1

🧠 Neurodegeneration

HYPOTHESES

2

PAPERS

14

KG EDGES

433

DEBATES

1

3D Protein Structure

🧬 HSP90AA1 — PDB 3HEF Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.45

Clinical Stage

Phase III

Target Class

Chaperone

Safety

0.50

Druggability Analysis

Drug Development0.45

Structural Tractability0.95

Target Class0.50

Safety Profile0.50

Key Metrics

PDB Structures:

326

Known Drugs:

2

Approved:

0

In Clinical Trials:

0

Drug Pipeline (2 compounds)

Druggability Rationale: HSP90AA1 is highly druggable (0.80 score) due to its well-characterized ATP-binding pocket, extensive structural data (326 PDB structures at 1.17 Å resolution), and proven clinical precedent with investigational agents (Geldanamycin, 17-AAG) advancing to Phase 3 trials. The conserved nucleotide-binding site provides a validated molecular target for competitive small-molecule inhibition.

Mechanism: Small molecule inhibitor binding to ATP-binding pocket of chaperone

Drug Pipeline (2 compounds)

Known Drugs:

Geldanamycin (Investigational) — Cancer

17-AAG (Investigational) — Cancer

Structural Data:

PDB (326) ✓AlphaFold ✓Cryo-EM ✓

2K5B 2QF6 2QFO 2QG0 2QG2+321 more

UniProt: H0YJF5

🧬 3D Protein Structure

🧬 HSP90AA1 — PDB 3HEF Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

The main selectivity challenge is HSP90 isoform selectivity; HSP90AA1 shares high sequence homology with HSP90AB1 (cytoplasmic) and HSP90B1 (ER-localized), risking off-target effects and toxicity from pan-HSP90 inhibition. Selective binding pocket modifications or subcellular targeting strategies are needed to achieve isoform-specific inhibition.

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

5

Total Enrollment

213

By Phase

PHASE1: 7 · PHASE2: 1

17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Metastatic Kidney Cancer Completed

PHASE2 NCT00093405

Kidney Cancer

Interventions: tanespimycin

Sponsor: Memorial Sloan Kettering Cancer Center | Started: 2004-08

17-AAG and Irinotecan in Treating Patients With Locally Advanced or Metastatic Solid Tumors Completed

PHASE1 NCT00119236 n=48

Unspecified Adult Solid Tumor, Protocol

Interventions: tanespimycin, irinotecan hydrochloride

Sponsor: National Cancer Institute (NCI) | Started: 2005-05

Geldanamycin Analogue in Treating Patients With Advanced Cancer Completed

PHASE1 NCT00003969

Unspecified Adult Solid Tumor, Protocol

Interventions: tanespimycin

Sponsor: Cancer Research UK | Started: 1998-08

Chemotherapy in Treating Patients With Refractory Advanced Solid Tumors or Hematologic Cancer Completed

PHASE1 NCT00004065

Bladder Cancer, Breast Cancer, Colorectal Cancer

Interventions: tanespimycin

Sponsor: Memorial Sloan Kettering Cancer Center | Started: 1999-07

17-N-Allylamino-17-Demethoxygeldanamycin in Treating Young Patients With Relapsed or Refractory Solid Tumors or Leukemia Completed

PHASE1 NCT00079404 n=36

Acute Undifferentiated Leukemia, Recurrent Childhood Acute Lymphoblastic , Recurrent Childhood Acute Myeloid Leukem

Interventions: tanespimycin

Sponsor: National Cancer Institute (NCI) | Started: 2004-03

Geldanamycin Analogue in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma Terminated

PHASE1 NCT00019708 n=45

Extranodal Marginal Zone B-cell Lymphoma, Nodal Marginal Zone B-cell Lymphoma, Non-Hodgkin Lymphoma

Interventions: tanespimycin

Sponsor: National Cancer Institute (NCI) | Started: 1999-06

Phase 1, Dose-Escalation, Pharmacodynamic Study of IV CNF1010 in ZAP-70 Positive CLL Terminated

PHASE1 NCT00319930 n=10

Chronic Lymphocytic Leukemia

Interventions: CNF1010 (17-AAG)

Sponsor: Biogen | Started: 2005-05

17-N-Allylamino-17-Demethoxygeldanamycin and Bortezomib in Treating Patients With Relapsed or Refractory Hematologic Can Terminated

PHASE1 NCT00103272 n=74

Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Megakaryoblastic Leukemia (M

Interventions: tanespimycin, bortezomib

Sponsor: National Cancer Institute (NCI) | Started: 2005-04

Linked Hypotheses (5)

HSP90-Tau Disaggregation Complex Enhancement0.634

HSP90-Tau Disaggregation Complex Enhancement0.575

Membrane-Localized HSP90 Disruption0.455

Phosphorylation-State Dependent Inhibition0.455

Allosteric Pocket Exploitation for Tau-Specific HSP90 Modulation0.455

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

associated with (1)

HSP90AA1→neurodegeneration

co discussed (6)

APOE→HSP90AA1HSPA1A→HSP90AA1DNAJB1→HSP90AA1HSP90AA1→ST6GAL1HSP90AA1→FKBP5

▸ Show 1 more

HSP90AA1→FUT8

interacts with (6)

HSPA1A→HSP90AA1HSP90AA1→HSPA1AHSP90AA1→DNAJB1HSP90AA1→FKBP5DNAJB1→HSP90AA1

▸ Show 1 more

FKBP5→HSP90AA1

regulates (1)

HSP90AA1→HSP90-Tau Disaggregation Complex Enhancement

therapeutic target (6)

AKT→HSP90AA1PI3K→HSP90AA1MAPK3→HSP90AA1JUN→HSP90AA1PTGS2→HSP90AA1

▸ Show 1 more

HIF1A→HSP90AA1

Debate History (1)

Should HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1) be priorit2026-04-21