Small molecules that competitively displace tau-stabilizing immunophilins (FKBP51) from HSP90 while recruiting tau-destabilizing co-chaperones (FKBP52), reprogramming HSP90 complexes from tau-protective to tau-degrading without inhibiting HSP90's essential functions.
Auto-built from this analysis's top knowledge-graph edges.
graph TD
FKBP5["FKBP5"] -->|protein interactio| HSP90AA1["HSP90AA1"]
FKBP51["FKBP51"] -->|stabilizes| tau["tau"]
FKBP52["FKBP52"] -->|destabilizes| tau_1["tau"]
SAFit_compounds["SAFit compounds"] -->|targets| FKBP5_2["FKBP5"]
FKBP5_3["FKBP5"] -->|protective against| tau_protein_aggregation["tau protein aggregation"]
FKBP51_4["FKBP51"] -.->|inhibits| HSP90AA1_5["HSP90AA1"]
style FKBP5 fill:#ce93d8,stroke:#333,color:#000
style HSP90AA1 fill:#ce93d8,stroke:#333,color:#000
style FKBP51 fill:#4fc3f7,stroke:#333,color:#000
style tau fill:#4fc3f7,stroke:#333,color:#000
style FKBP52 fill:#4fc3f7,stroke:#333,color:#000
style tau_1 fill:#4fc3f7,stroke:#333,color:#000
style SAFit_compounds fill:#4fc3f7,stroke:#333,color:#000
style FKBP5_2 fill:#4fc3f7,stroke:#333,color:#000
style FKBP5_3 fill:#ce93d8,stroke:#333,color:#000
style tau_protein_aggregation fill:#4fc3f7,stroke:#333,color:#000
style FKBP51_4 fill:#4fc3f7,stroke:#333,color:#000
style HSP90AA1_5 fill:#4fc3f7,stroke:#333,color:#000No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for FKBP5 yet. Search RCSB →
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for FKBP5.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF human iPSC-derived cortical neurons harboring P301L MAPT mutations are treated with a 100 nM concentration of a small molecule designed to competitively displace FKBP51 from HSP90 while preferentia | Soluble tau concentration will decrease by at least 40% in compound-treated neurons compared to vehicle control at 72 hours post-treatment. | — no observation — | pending | 0.65 |
| IF male 3xTg-AD mice (6 months old) receive daily intraperitoneal injections of a selective FKBP51-displacing/FKBP52-recruiting compound at 10 mg/kg for 28 days, THEN hippocampal insoluble tau aggrega | Sarkosyl-insoluble tau will be at least 35% lower in compound-treated 3xTg-AD mice relative to vehicle controls after 4 weeks of treatment. | — no observation — | pending | 0.55 |